Allergies and allergic diseases

Allergy

Introduction, classification

The body has no processes and reactions focused only on damage. All of them have an adaptive and protective character and only under certain conditions or defects in them can have a damaging effect and serve as a basis for the development of pathological processes. This fully applies to allergies as well.

However, from the time of Clemence Pirke, who introduced the term allergy in 1906, which means a different action (allos - a different ergon - action) until today, allergies refer only to damage resulting in disease. Moreover, the evolution of the idea of allergy as a damaging reaction has become more and more specific over time. For example, in 1906 K. Pirke gave the following definition of allergy: "Changed sensitivity to substances with which the body had previously come into contact". In 1994, A.D. Ado already defined allergy as "the immune response of the body to any substances of antigenic or haptogenic nature, accompanied by damage to the structure and function of cells, tissues and organs".

A reflection of this view is also the classification of the leading mechanisms of tissue damage in immune processes, proposed by Gell and Coombs in 1969:

• Type I - Immediate hypersensitivity reaction (ITH)
• Type II - a complement of dependent cytotoxic reactions (rheumatoid arthritis, myasthenia, autoimmune hemolytic anemia, SKV, etc.).
• Type III - immunocomplex reactions (diffuse glomerulonephritis, hemorragic vasculitis, etc.).
• Type IV - delayed hypersensitivity reactions (DTH).

In recent years, another type 5 has been isolated, which is associated with the presence of antibodies to physiologically important determinants of the cell membrane - receptors (acetylcholine receptors, beta-adrenor receptors, insulin receptors, receptors for TTG). The reaction of these antibodies with the receptors can either stimulate or block the effect of these cells.

It is important to note that the secretion of type 5 allergic reactions calls into question the necessity of damage to structure and function in an allergy.

Traditionally, of all the variants of tissue damage in immune processes, types I and IV are associated with allergies - immediate hypersensitivity and delayed hypersensitivity. It is these two types of reactions that seem to be the classic ones for allergies that need to be understood in more detail.

Reactive (IgE) type of allergic reactions (hypersensitivity of immediate type, ITH)

Protective role of ITH

Until a certain point, a ITH is a typical example of a humoral immune response. The main actors in ITH are B-cells, Tx2, IL-4, IL-5, IgE, basophils, mast cells (tissue analogues of basophils), eosinophils. Unlike other immunoglobulins, IgE are highly cytophilic, i.e. they can attach to the cell (Fc-fragment) at one end and bind the antigen (Fab-fragment) at the other end. These immunoglobulins play a major role in allergic reactions, which led them to have a second name - reactions. This name reflects their main difference from other immunoglobulins, which are called protective or protective. IgE participate in (reactive) defense reactions, but do not perform it themselves. The same applies to the participation of IgE in pathological processes.

Under the influence of T-helpers of the second type, producing interleukins 4 and 5 (which have a key role in the development of allergies) and the antigenic stimulus is the activation of B-cells towards the synthesis of IgE, specific to this antigen. It should be noted that in both normal and pathological conditions, IgE synthesis occurs mainly in the lymphatic tissue associated with mucous membranes, including mesenteric and bronchial lymph nodes. Lymfoid tissue of mucous membranes is also the main producer of IgA. Data on the antagonistic relationship between IgA and IgE are very interesting, which may be due to the priority in the lumen of mucosal antigens overseen by these immunoglobulins. It is supposed that the peculiarity of microenvironment of lymphoid tissue of the mucosa is the main factor that orients B-cells towards IgA and IgE synthesis. It is the mucous membranes, especially the intestines, which are the place where these immunoglobulins realize their protective functions.

IgA has an independent role in the protection of the mucous membranes, neutralizing the penetrating pathogens. The neutralization effect is manifested by immobilization of the microorganism, limitation of its overcoming the tissue barrier, weakening of the connection of the microbe with the mucosa, which contributes to its removal.

Another mechanism is at the heart of the protective action of IgE, which is focused mainly on parasites (such as helminths). As already mentioned, IgE do not have an independent protective effect, but serve as initiators of reactions aimed at the destruction and removal of parasites. In this respect, their predominant presence in the mucosa and especially in the intestinal mucosa is symbolic, since the main localization of parasites is the gastrointestinal tract.

Previously, it was believed that receptors to IgE are found only in basophiles and mast cells, but recently, IgE receptors are found in other cells (neutrophils, macrophages, lymphocytes, platelets, etc.), but unlike the receptors of mast cells and basophiles, they are low affinity (they bind IgE less firmly). This allows us to focus on basophils and mast cells in the future.

So, IgE is fixed on mast cells and basophiles. The concentration of IgE on the membranes of these cells can reach 400,000 IgE molecules per cell. It is important to remember that fixation of IgE on mast cells is very strong and long (up to 12 months), in contrast to free IgE half-life of which is 2 days. This is the meaning and the end of the stage of sensitization to this specific antigen, which is a prerequisite for allergic reactions. At the same time, IgE is fixed on the parasites (Fab-fragment).

We considered the immune system response to primary contact with the parasite antigen, or the immunological stage of allergic reactions. As can be seen from the above, apart from fixing IgE on the parasite, there are no other effects aimed at its destruction and removal. Therefore, it continues to exist, causing repeated antigenic irritation.

Repeated contact of the antigen with IgE fixed on mast cells and basophiles causes degradation of these cells and release of a large number of biologically active substances (histamine, serotonin, platelet activation factor, leukotrienes, prostaglandins, chemotactic factors, proteoglycans, enzymes, etc.). This is the so-called biochemical stage of ITH. The protective meaning of this stage is realized in two directions: a) attraction of eosinophils to the reaction site; b) smooth muscle spasm, edema and increased secretion of mucosa glands. Both of these mechanisms are protective in nature, although the second mechanism is considered to be the pathophysiological stage of ITH and is associated with clinical manifestations of allergic diseases.

However, let us consider these reactions. The migration of eosinophils to the reaction zone plays a crucial role in antiparasitic protection. The fact is that eosinophils are the main cells in the immune system that perform extracellular cytolysis. All other effector cells are focused on intracellular digestion of pathogens, however, in the analyzed case the pathogen is so large that intracellular digestion is impossible and eosinophils are the only acceptable effectors for such cases. Eosinophils contain a large number of substances with proteolytic properties (peroxides, acid phosphatase, collagenase, elastase, glucoronidase, cathepsin, RNA-az, myeloperoxidase, etc.). However, the main biologically active substance of eosinophils is the main alkaline protein, which performs extracellular cytolysis.

Eosinophils have a great affinity for the Fc fragment of IgE. Fixation of eosinophils to IgE triggers the mechanism of extracellular cytolysis and destruction of the parasite due to degradation and release of proteolytic substances. Additional mechanisms for the fastest sanitation of the body from the parasite are swelling and increased secretion of mucous membrane glands (especially important for parasites with mechanisms of fixation to the mucous membrane) and the reduction of smooth muscle muscles, peristaltic movements expelling the parasite or products of its decay from the body.

Thus, the ITH, which is associated with the majority of allergic diseases, is essentially an immune response option designed to protect against pathogens that require an extracellular cytolysis in the final stage of their immune response.

Damaging role of ITH

So why does a ITH so often transform into its opposite and serve as the basis for damage typical of allergic diseases? Unlike other immune response options, there are many more risk factors in the mechanisms of ITH implementation that easily transform a protective reaction into its opposite.

An attempt to characterize these "Achilles' heels" of ITH would be worthwhile.

Perhaps we should start with extracellular cytolysis and its main protagonist eosinophils. Extracellular cytolysis is a very powerful and dangerous reaction for the body, which is relatively harmless when realized outside the tissues (lumen of the intestinal tube, bronchi, etc.) and is absolutely unacceptable for the tissues, because it is always accompanied by massive destruction. From this perspective, it is clear why the main ITH participants are localized predominantly in the mucosa. In all other immune response variants, this risk factor is absent, since the final stage is either passed by intracellular cytolysis in the effector cells (micro- and macrophages) or in the target cells by initiating cytotoxic lymphocytes apoptosis in them. Thus, the final stage of ITH - extracellular cytolysis - carries a high risk of damage if this reaction is realized in tissues. And such conditions exist. They are as follows. Eosinophils circulate in the blood from half an hour to several hours, after which they are localized in the tissues, where their lifespan is up to 24 days. Eosinophils also have receptors to IgE, which can be fixed on intracellular eosinophils and at repeated contact with them the antigen can cause the whole chain of events described above, ending with extracellular cytolysis, directed to their own tissues. This explains the severity of the course of eosinophilic pneumonia, as it is destructive pneumonia.

The next risk factor is a long and strong fixation of IgE on fat cells. The main place of localization of mast cells - serous membranes, spleen, epithelium and submucosal layer of gastrointestinal, respiratory and urogenital tract, skin, connective tissue of capillary clutches - is precisely in the places that are associated with the main clinical manifestations of allergy. Most often, the secretion of IgE and its binding by mast cells occurs in the same areas of the mucous membrane, but it is proved that there is a single system of lymphatic tissue of the mucous membranes, which creates conditions and determines the possibility of migration of activated (sensitized) cells to other regions. Sensitization of the gastrointestinal tract therefore has a fairly rapid effect on the mucous membrane of the respiratory tract and vice versa. On the other hand, specific IgE entering the bloodstream can be fixed by fat cells of the skin, connective tissue of the capillary clutches. Thus, the long-term existence of sensitized (loaded with specific IgE) mast cells of different localization and determines the possibility of allergic diseases in case of repeated contact of these cells with the antigen.

The next risk factor is the wide prevalence of IgE receptors on other cells (neutrophils, macrophages, lymphocytes, platelets, etc.). In contrast to the receptors for mast cells and basophils, they are low affinity (the second type of receptors to IgE). However, the affinity of these receptors, as well as the number of cells carrying them, may increase. Macrophages and platelets deserve special attention in the context of the discussed problem. IgE can react with membrane receptors of macrophages and directly cause the effect of antibodies-dependent cell cytotoxicity. Thrombocytes, in addition to their main function - regulation of blood aggregation, are the depot of biologically active substances (serotonin, cationic proteins, proteases, etc.). The presence on them receptors for specific IgE at repeated contact with antigens can contribute to their degradation with all the ensuing consequences and clinical manifestations of allergic diseases caused by structural and functional damage. Rather wide distribution of autoimmune thrombocytopenia may be connected with IgE fixation on platelets.

Another important factor is the presence of the biochemical stage of ITH, which is based on the release of a large number of different biologically active substances (BAS). If the mechanisms of their degradation are disrupted, the long-term existence of high concentrations of biologically active substances in itself, without the antigen, can cause the degradation of basophils and fat cells, the process becomes self-sustaining and uncontrollable, leading to damage and clinical signs of allergic diseases. One more fact is important here. At present, there is a unanimous opinion that allergic diseases can develop only as a result of the failure of immunoregulatory mechanisms and, above all, the violation of immunoregulatory cells function. In this respect, histamine deserves the most attention. Histamine activates the suppressor functions of CD8 cells through H2-receptors; inhibits cytotoxic and helper activity of T-lymphocytes; inhibits the response to mitogens, synthesis of antibodies, production of a factor depressing the migration of macrophages. These histamine effects play a positive role in the reverse development of ITH; however, if the mechanisms of inactivation and degradation of histamine are disrupted, these same properties cause immunoregulatory mechanisms to fail.

The risk factors presented here make it clear that ITH can indeed easily, compared to other immune response options, transform into their opposite and serve as a basis for allergic diseases. It should be stressed that not all risk factors are presented here, but the most obvious ones lying on the surface. In fact, there are much more of them, but this is the subject of a separate conversation.

However, acquaintance with risk factors does not give an answer to the main question - what is the reason for the transformation of ITH from protective to damaging. Logically, the impression presented here is that the primary trigger for allergic diseases is contact with parasites, particularly helminths, and that this contact leaves a state of sensitization for a long time, if not for life. This thesis, however, does not stand up to the criticism, because it does not correspond to the life expectancy of sensitized cells, should provide for a mass spread of worm infestation, and most importantly, does not correspond to clinical practice that shows a wide spread of allergic diseases associated with a variety of antigens. At the same time, the role of primary parasitic infestation cannot be completely excluded, and in all cases of allergic diseases, especially with eosinophilia, examination in this direction is necessary.

In order to find the causes, it is necessary to return to the origins of the doctrine of allergy.

In 1923, A. Coca and R. Cooke introduced the concept of "atopy" to describe a hereditary predisposition to allergic diseases. Carl Dresler defined atopy in 1988 as "a genetically determined predisposition to pathological immune reactions in response to stimuli (allergens) that are harmless to most people (80-90%)". Currently, atopy is understood as an allergic disease associated with IgE.

Thus, the search for the main causes of allergic diseases can be initially narrowed to clarify the factors of hereditary predisposition, including excessive synthesis of IgE, as the central figure in the ITH.

Currently, there are some advances in understanding the causes of IgE over synthesis. The key role of Type 2 T-helpers (Tx2) in the development of ITH has been established. There is a shift in the differentiation of "naive" T-helpers (Tx0) in persons predisposed to allergic diseases towards the preferential formation of Tx2, whose interleukins (IL-4, IL-5, IL-3, IL10) under certain conditions facilitate the switch of B-lymphocytes to IgE synthesis instead of IgG. There are speculations (A. A. Yarilin, 1999) that factors intensifying the differentiation of Tx0 into T-helpers of the first type (Tx1) will inhibit the development towards Tx2 and may become an effective treatment for allergic diseases. Such factors should include, first of all, IL-12 and interferon-gamma.

Besides this main way of regulation of IgE synthesis, there are additional ones. It was found that T-cells produce factors that enhance and inhibit the synthesis of IgE (substances of protein nature with a mass of 15000-60000). The strengthening factor produces CD23 T-cells; the suppressing factor is CD8 T-cells. The important role of the lymphocyte suppressor fraction in the pathogenesis of allergic diseases is evidenced by the data (G.V. Poryadin, 1999) that in 68% of patients with atopic bronchial asthma the induced suppressor activity of lymphocytes was cancelled completely already in the first 5 years of the disease.

Botvineva V. V. (1998) presents data that the IgG deficit allows IgE to realize its membrane attack action. We also find evidence of this in A.A. Yarilin (1999): since IgG and IgE antibodies are identical in specificity to the antigen that caused them, IgG binds the antigen (allergen) and blocks ITH manifestations (blocking antibodies). This is the basis for one of the areas of allergy treatment and prevention - strengthening the IgG response with adjuvants that increase the immunogenicity of the allergen. IgG4, with which the main role in blocking IgE is associated, deserve special attention in this respect. It is significant that IgG4 deficiency is very often accompanied by recurrent and chronic infections. It seems that IgG4 deficiency not only increases the clinical manifestations of allergic diseases, but also contributes to their development, since it is accompanied by immune deficiency.

To some extent, the condition of skin and mucous membranes, especially the latter, should be attributed to hereditary factors. These are the two most powerful barriers, violation of permeability, which leads to the entry of antigens in normal conditions, either not coming in or coming in only limited. To some extent, this thesis is confirmed by the frequent development of allergies to exotic food products (citrus, seafood, etc.), i.e. to antigens that are not included in the normal diet of the population of a particular area. At the same time, most often violations of the barrier function of skin and mucous membranes are an acquired factor, which may be associated with the action of chemical, physical and biological initiatives. Intestinal infections are of particular importance in this regard. It seems that the intake of "forbidden" in the normal state of skin and mucous membrane antigens disorients the immune system when choosing the best immune response to them, and it is possible to choose extracellular ITH cytolysis, which, provided the excessive circulation of IgE promotes allergic diseases. It is possible that the orientation of the immune response to ITH with extracellular cytolysis is associated with the fixation of antigens that have penetrated through the mucosa and skin on cells and tissues of the body. A. A. Yarilin (1999) provides very interesting information on the circumstances that contribute to the manifestation of antigen allergenicity: the small size of the antigen molecule, allowing it to penetrate through the mucous membranes; a low dose, which favors the formation of Tx2; intake through the mucous membranes - concentration of the main population of fat cells and the place of IgE migration. Generally, the state of the mucous membranes is one of the most important, if not the main, factors for the development of allergic diseases, since most antigens come through the mucous membranes; the microenvironment of the mucous membranes is the most powerful of the known factors of differentiation of Tx0 to Tx2 and switching of B-cells to IgE synthesis. This is also facilitated by IL-4, which is most likely to be produced by fat cells of the mucous membranes.

The data of G.A. Samsygina (2000) and D.G. Soldatova (1997) are essential in understanding the causes of ITH.

In Samsygina's opinion, changes in the immune status of chlamydia infection are very close to those of ITH, including hyperIgE and eosinophilia, and chlamydia infection may be a real candidate for one of the trigger mechanisms of allergic diseases. This is all the more likely because according to V.I. Pokrovsky and I.N. Gnutov (1996) the true spread of chlamydia infection is unknown, but it is widespread among domestic and wild animals.

However, viral infections, in particular respiratory pathogenic viruses, are the most realistic candidates for ITH cause factors. Joint research conducted by the Research Institute of Pulmonology and the Lomonosov Institute of Virology. D.I. Ivanovsky Institute of Virology (D.G. Soldatov, 1997) showed that respiratory viruses, especially respiratory syncytial viruses, influenza and parainfluenza viruses have a powerful sensitizing effect, causing a marked rise in viral specific IgE in the blood. However, in 5-6 days the competitive relationship of interferons and interleukins in influence on IgE synthesis led to normalization of IgE level. Respiratory syncytial viruses (PC viruses) were an exception: they induced a steady and pronounced rise of IgE level in practically healthy persons. According to D.G. Soldatov (1997), this is due to the oppression of PC viruses with interferon products and he believes that PC infection may induce the development of atopic predisposition in healthy individuals. However, in our opinion, similar mechanisms may also exist for other viral infections (herpesviruses, adenoviruses, enteroviruses, rheoviruses, etc.), since clinicians are well aware of the facts of exacerbation of atopic diseases against their background and have data on the dependence of IgE levels on the frequency and severity of relapses of herpes simplex, as well as on the marked sensitization effect of the Epstein-Barr virus. Especially since viruses (at least PC viruses) can activate the production of general and specific IgE to non-virus allergens. An additional argument in favor of the causal role of respiratory viruses in the genesis of GHBs is the increased release of histamine by basophils when they come into contact with these viruses (Clementsen P. et al., 1990).

Definition of immediate hypersensitivity.

This section concludes with a definition of a ITH that reflects the information and facts described above.

A ITH is a variant of a specific immune response that is implemented when necessary in the final stage of extracellular cytolysis. In the presence of certain conditions and failure of immunoregulatory mechanisms, which are often genetically determined, this variant of immune response focuses on damage to the body's own structures and underlies the formation of allergic diseases and other immunopathological options.

Delayed type hypersensitivity (DTH)

Protective role of DTH

The main protagonists of DTH are Tx1, macrophages, dendritic cells (Langerhans cells when the antigen enters through the skin), IL-2, interferon-gamma, tumor necrosis factor alpha (FNO-Alpha), lymphotoxin, granulocytic-macrophagal colony stimulating factor (GM-CSF).

DTH is a variant of cellular immune response, however, in contrast to the typical variant of cellular immune response, where the effector link is an antigen-specific cytotoxic lymphocytes, the effector link of DTH is an immune inflammation - inflammation that develops in response only to a specific antigen (specific inflammation). The need for this variant arose due to the presence of intracellular pathogens, the destruction and elimination of which is impossible with a typical variant of cellular immune response.

Cellular and humoral immune responses in their typical variant provide effective protection from the bulk of antigens, however, they do not overlap the entire spectrum of pathogens and evolution has created additional variants of these responses (ITH and DTH), which in combination with the main ones are oriented to all cases of life. Thus, the choice of the optimal variant of the immune response is entirely related to the characteristics of the pathogen. In the case of DTH, the importance of the presence of lipid components in the microorganism in the choice of this variant of immune response has been proved. Mycobacteria are a typical example of intracellular pathogens, in which the standard variant of cellular immune response is ineffective. It is on their example that it seems reasonable to disassemble the protective role of DTH.

When tuberculosis mycobacteria enters through the mucous membranes, it is absorbed and treated by dendritic cells (Langerhans cells through the skin). Dendritic cells transport peptide fragments of the antigen in the membrane molecules of GKGS class II to the nearest lymph node, where this antigen Tx0 is presented. In response to the antigenic stimulus, they are activated and produce IL-2, which promotes their proliferation and differentiation into the Tx1 antigen sensitized to this antigen. These lymphocytes, also called pre-dactivated Tx1, leave the lymph node and move to different parts of the immune system. This ends the primary contact with the antigen, the main consequence of which is the appearance of lymphocytes sensitized to a specific Tx1 antigen. The sense of sensitization lies in the formation of blank forms of lymphocytes (pre-dactivated Tx1). These lymphocytes practically do not secrete cytokines, which play a major role in the development of immune inflammation.

By analogy with ITH, the Tx1 sensitized cells can be called reactive cells, since they do not directly perform the effector function, but initiate the reaction of other components of the immune system, resulting in a pathogen-specific immune inflammation.

The re-injection of the antigen implements the following chain of events. In the place of re-introduction, the antigen is absorbed by macrophages, which present the antigen to sensitive Tx1 cells. The result of repeated contact of these cells with the antigen is the completion of their differentiation into the so-called "inflammatory" Tx1 cells, which begin the active production of cytokines - inducers of immune inflammation (IL-2, interferon-gamma, lymphotoxin, FNO-Alfa, GM-CSF). These cytokines, especially interferon-gamma, cause a pronounced activation of macrophages and stimulation of their ability to destroy the pathogen. In turn, the cytokines secreted by activated macrophages cause migration to the place of localization of the pathogen monocytes, which infiltrate this place and actively join the macrophages in their attempt to destroy and eliminate the pathogen. If the joint efforts reach the goal, the DTH reaction ends there, the infiltration is dissolved and the immune inflammation is eliminated. However, quite often, especially in the case of the tuberculosis pathogen we are considering, these efforts are not enough and granuloma begins to form. A.A. Yarilin (1999) gave a very precise description of granuloma: "In fact, granuloma is a newly formed morphological structure designed to isolate a pathogen or other foreign object, the destruction and elimination of which is impossible".

Granulema is a morphological structure with the causative agent in its center, infected macrophages, merged macrophages (giant cells), cell detritus, and on the periphery a cell barrier mainly made of T-lymphocytes, separating the pathogen control arena from healthy tissue. Further evolution of granuloma is a destruction starting from the center, which in case of pulmonary tuberculosis forms a cavern.

To conclude the description of the protective role of DTH, there are two important points to consider, which will help to be more specific in those situations where this reaction is the only choice in protecting the body from the pathogen. These are the migration of monocytes to the location of the pathogen and the presence of giant cells (merged macrophages). DTH and its effector mechanism - immune inflammation is realized only in cases when the "killing force" of one or more macrophages is not enough to destroy and eliminate the pathogen. This is the meaning of immune inflammation - attraction of specifically oriented additional forces (monocytes) for collective elimination of the pathogen. Moreover, attempts at destruction are not only joint efforts of many macrophages aimed at the pathogen, but also their fusion into one large cell to enhance the lytical potential. The coordinating role here seems to be played by T-helpers. The formation of a cellular barrier around the granuloma is therefore more likely to be due to T-lymphocytes.

Damaging role of DTH

The specificity of DTH is immune inflammation and is a damaging mechanism. Unlike ITH, it is not a risk factor that can become damaging under certain conditions or defects in the immune system. All that is needed to achieve the damaging effect of immune inflammation is the failure of attempts to destroy and eliminate the pathogen.

Thus, the damaging effect of DTH is associated not with certain defects in the immune response or heredity, but with the peculiarities of the antigen itself and its resistance to the effector mechanisms of the immune system.

Another mechanism of damage is the location of the granules themselves, which, having a mechanical effect on tissues and organs can cause damage and functional defects.

Definition of the concept of delayed type hypersensitivity.

DTH is a variant of a specific immune response, which is implemented if necessary in the final stage of immune inflammation. The damaging effect of DTH is fully related to the features of antigenic irritation.

Allergy and immune system

One of the mandatory conditions for allergic reactions is repeated contact of the antigen with the body structures sensitized to this antigen. At the same time, repeated contact is also the essence of immunity (secondary immune response). A. A. Yarilin (1999) formulated this very clearly: "The word immunity, which gave the name to the science of immunology, does not mean immune processes that counteract infectious agents, but a state of resistance to their action that prevents the development of infection". This is the essence of immunological memory, which is formed after the primary immune response and is essentially a high sensitivity (sensitization) and immediate readiness to react to the reintroduction of this particular antigen.

There are the following immune response options:

1. Humoral immune response.
2. Hypersensitivity of the immediate type (ITH).
3. Cellular immune response.
4. Hypersensitivity of the delayed type (DTH).

We would like to emphasize four variants of immune system responses, depending on the quantity and quality of antigenic irritation, designed to protect against foreign antigens and preserve body freedom in life. Humoral immunity - protection against bacterial infections and foreign proteins; ITH - a variant of humoral immunity if necessary in the final stage of extracellular cytolysis; cell immunity - protection against viral infections and foreign cells; DTH - a variant of cellular immune response if necessary in the final stage of immune inflammation.

A protective allergic reaction occurs when the immune system is unable to neutralize the pathogen at the first attempt. It is for such cases of immunity failure that allergy, which can still be called the second echelon of immune protection, is intended, since its effector mechanisms are implemented only on repeated contact with the antigen.

Thus, there are no fundamental differences between immunity and allergies. The concept of allergy reflects the historical stage of immunology development; the stage when the available amount of knowledge did not allow comprehending this phenomenon as one of the typical variants of the immune response, which predetermined the appearance of the term allergy (another action). At the same time, the terms allergies, allergens and sensitization should not be abandoned as a guide for a physician on those immune response options that are much more often than others accompanied by the development of pathological processes - allergic diseases.

It seems reasonable to give, in our opinion, a modern interpretation of the concept of allergies.

Allergies are immune response variants based on ITH or DTH and which, due to their features, are significantly more often accompanied by structural and functional damage of cells, tissues, organs when repeated contact with the antigen than others.

At the same time, if by allergy we understand the pathological orientation of not only ITH and DTH, but also cellular and humoral immune responses, then the classification of Gell and Coombs will be valid, but such interpretation seems inappropriate due to the following circumstances. First, in practical medicine, the circle of nosologies included in the group of allergic diseases has been quite clearly formed and it makes no sense to change these traditions. Secondly, autoimmune and immunocomplex diseases also have a traditional circle of nosologies, which orients the doctor in a very specific diagnostic and therapeutic tactics, and there is no point in combining them with allergies. Third, and most importantly, the anaphylactic (ITH), cytotoxic, immunocomplex, cellular-mediated (DTH) and antireceptor types of immune damage are fundamentally different mechanisms, each requiring its own diagnostic, therapeutic and preventive approaches. It is on this path that we see real opportunities for progress in the treatment of diseases associated with these mechanisms.

It seems expedient to give a brief description of immune response options and the main stages of protection against antigenic aggression for a clearer orientation in immune damage mechanisms.

Evolution has created a perfect and deeply echelonized defense system to protect its own antigenic constancy and ensure body freedom of life.

As a rule, the first contact with antigen occurs on skin and mucous membranes. The state of these barriers and the peculiarities of the antigen determine the condition or failure of this first line of defense and the need to implement the remaining stages of the immune response. This is a very important stage that predetermines the correct orientation of the immune response or the possibility of developing its damaging variants. According to I. S. Gushchin (2000), "the state of histogematic barriers (namely, skin and mucous membranes) is a factor making an allergic response unnecessary or, on the contrary, forcing a response. Previously mentioned features of the antigen that make it an allergen - small molecule size and low dose. Such characteristics of the antigen determine the possibility of its unobstructed penetration through the mucous membranes and the orientation of differentiation Tx0 to Tx2 with the dominance of IgE secretion.

However, let us return to the first stage of immune protection - the skin and mucous membranes and their lymphatic system. Depending on the peculiarities of the antigen and the state of this barrier, two options are possible for further development of events. If the antigen damages tissue structures - a typical protective inflammatory reaction develops; if no damage occurs - the antigen penetrates the nearest lymphatic structures.

Immune response in case of inflammation

Inflammation is the first line of immune protection and is realized by cells and humoral factors, for which the stimulus of their functional activity is the damage itself. However, it is not only the damage that initiates inflammation. We cannot exclude the participation in this process of bacterial lipopolysaccharides and peptidoglycans, which are not typical for normal cells. However, we believe that the most universal target for the orientation of immunocompetent cells and humoral factors on the implementation of the inflammatory reaction is the end sugars (mannose) of membrane glycoproteins and glycolipids, released as a result of damage, transformation, increased proliferation or aging of the cell. This is a so-called "universal foreigner" without differentiation into individual antigens. A. A. Yarilin (1999) is quite right, who says that "on the level of the first line of defense the concept of antigen makes no sense". We will not dwell on the details and stages of the inflammatory process, which are quite well described and known to everyone. We will single out only the main thing necessary for understanding the logic of immunity and possible mechanisms of its participation in damage.

The main protagonists of inflammation are neutrophils, macrophages/monocytes, NK cells, sometimes eosinophils, complement system, inflammatory cytokines (IL-1, IL-6, FNO-Alpha, interferons), acute phase proteins, BAS (kinins, histamine, heparin, prostaglandins, leukotrienes, etc.). In their interaction, they help localize and destroy the pathogen. Neutrophils and macrophages/monoses take the main blow in this process. Neutrophils not only phagocyte, but can also perform extracellular cytolysis, as well as the secretion of cytokines and other BAS. Due to the possibility of developing extracellular cytolysis, long-term inflammation may contribute to the damage of their own tissues and acquire all the features of the local autoimmune process, especially if eosinophiles, known for their priority in the implementation of extracellular cytolysis, are involved in the elimination of the pathogen.

Participation in inflammation of macrophages/monocytes is extremely important. It becomes clear that such a significant role of these cells in the presentation of the antigen and the triggering of a specific immune response. By primary contact with the pathogen, macrophages/monocytes not only participate in its elimination, but also by presenting its antigens initiate the addition of the next more powerful stage, which includes the entire arsenal of the immune system (cellular, humoral immunity, ITH, DTH) already specifically oriented to these antigens. Naturally, this applies to thymus-dependent antigens, but recently data have also emerged on the existence of thymus-dependent antigens. The specific stage is not only a more powerful, but also a higher quality stage of protection, because the specific orientation practically excludes the possibility of damage to normal body structures, which exists under normal inflammation. The specific stage limits the possibility of organism damage by a pathogen. It should be thought that connection of a specific stage eliminates the need for an inflammatory reaction, and the time of deployment of this stage determines the duration of the clinical picture of the disease. The logical conclusion of this stage is not only complete and high-quality sanitation from the pathogen, but also the creation of immunological memory, providing operational protection in case of repeated exposure to the antigen without any damage to the body.

Thus, the long existence of the inflammatory process (chronic inflammation) clearly indicates the failure of the specific stage of the immune response associated with structural or functional defects in the immune system and is always a risk of immunopathology.

The above data allow to present more clearly the logic of interrelation of non-specific and specific in ensuring rational and qualitative immune response. At the same time, there is no consensus on the central role of macrophages/monocytes involved in the inflammatory response in the initiation of a specific stage. A. A. Yarilin (1999) believes that these cells cannot significantly participate in the presentation of the antigen because they do not migrate to lymph nodes and in the activated state divide the antigen into too small fragments. However, the known fact of a better immunity after the disease than the vaccination suggests that the presentation of the antigen from the inflammation center provides a better immune response than other sources. At least for the skin, such cells are known to be Langerhans cells or white epidermyocytes, which, capturing in the focus of the antigen, migrate to lymph nodes along the way transforming into dendritic cells. As for mucosa - further research is required, but the importance of macrophages/mono-cytes in this process cannot be ignored at this time.

Immune response in the absence of inflammation

Marked features of the antigen or violation of the barrier role of skin and mucous membranes contribute to the transit of the pathogen into lymphatic structures, where it meets with immunocompetent cells. This pathway is much more dangerous and significantly increases the risk of immunopathology formation. This is due to a number of conditions and circumstances. Let us analyze some of them. The point is that lymphatic structures are the place where full variants of immune response are formed. If we can put it this way, it is the "intimacy" where the entry of strangers is undesirable. Contact with extraneous (antigens) is carried out through the presentation, i.e. in a convenient way. Contact of the "wild" antigen with the entire repertoire of immunocompetent cells in the lymph node may cause a violation of the usual and most rational logic of interaction of immunocompetent cells and become a risk of immunopathology, including allergies. From this perspective, it is clear why the low molecular weight of the antigen, which facilitates its transit through the mucosa into lymphatic structures, is one of the conditions for allergenicity of this antigen. Direct contact of low doses of this antigen with T cells can cause the formation of immunological tolerance, since it is well known that the induction of T-cell tolerance requires 100-1000 times less antigen doses than for mature B-cells (G.W. Siskind, 1988).

Direct contact with the lymphatic structures of pathogens is especially dangerous, since their damaging potential is realized at the place where the immune response is formed and, along with a violation of the logic of interaction of immunocompetent cells, can break this logic directly damaging them. The risk for human diseases with such mechanism (syphilis, tuberculosis, brucellosis, toxoplasmosis, lymphoproliferative diseases, etc.) is well known. At the same time, it is difficult to imagine skin and mucous membrane areas free from the control of antigen-presenting cells (APC), which would create the possibility of antigen contact in untreated form with lymphatic structures. This is most likely to be possible under certain conditions:

• Significant defects or long-term irritation of the skin and mucous membranes;
• features of the antigen that allow it to "slip away" from the APC cells;
• Intense or frequent contact of the antigen with the APC, exhaustive antigen capabilities;
• functional or structural defects of APC.

In conclusion of this section we can conclude that the most dangerous for the body in terms of the possibility of immunopathology and allergic diseases is direct contact of the antigen with the immune system, bypassing the protective inflammatory response. At the same time, the most optimal two-stage reaction of the immune system (inflammation is a specific immune response) also carries the possibility of immune damage. At the same time, the central link, it seems to us, is the quantity and quality of the antigen that starts and orients the immune response adequate to the antigenic irritation. The quality of primary contact also determines the quality of the immune response. Monocytes are the most available for control from this cell group. It is thought that studying the relationships between immunoglobulins (in particular, IgE) and monocytes can provide indirect but valuable information about the quality of the mechanism of representation of antigens and will serve as an additional criterion for diagnosis and prognosis of allergic diseases (immunopathology), as well as the development of new allergy treatment options on this basis.

Pseudoallergy

Subsequent consideration of the principles of clinical diagnosis of allergic diseases and the resulting pathophysiologically sound therapy is impossible without a brief mention of the so-called "pseudoallergy". The emergence of this term is associated with the identification of A. D. Ado in 1969 in addition to the true allergic reactions of false allergic reactions that we have considered. In terms of external manifestations, pseudoallergic reactions resemble true allergic reactions, but the development of the clinical picture in them occurs without previous sensitization to the pathogenic factor. In other words, in the pathogenesis of false allergy there is no presence of immunological mechanisms, which is an important difference between true and false allergic reactions. In other words, pseudoallergic condition is based on non-specific liberalization of mediators from target cells of allergy, induced by direct contact of certain substances with cell membranes (L.V.Luss, 1999). However, at present, a number of others are considered as well as the abovementioned basic cellular mechanism of false allergy.

In this connection, three groups of mechanisms of pseudoallergic reactions development can be distinguished.

The first group of mechanisms is actually related to hyperproduction of the main mediator of histamine allergy. Nonspecific liberalization of histamine from the allergy target cells can be achieved by destroying cells under the influence of X-rays, infective agents, chemicals (cytotoxic release) or through activation of the cell receptor apparatus (cytotoxic release) by "liberators" of the mediator, which include calcium ions, trypsin, neuropeptides, X-ray-contrast substances, etc. In the case of pseudoallergenic reactions, the allergy target cells are allergic.

It should be kept in mind that pseudoallergic symptoms in a person develops under the condition of increase of free histamine concentration in plasma. In this case, the normal plasma content of histamine is extremely low (1 nanogram/ml).

The increase of histamine level in the blood may be associated with a pathology of the process of its inactivation. Violation of histamine inactivation may occur with prolonged use of some rich products, taking a number of medications, diseases of the liver and intestines, reducing the activity of histaminase.

The second group of mechanisms of pseudoallergic reactions is associated with the activation of the complement system. This may be, for example, in the acquired shortage of some inhibitors of this system. A typical example is the appearance of "allergic" symptomatology under stress.

And the third pathogenetic group may occur in cases of arachidonic acid metabolism disorder. The action of some compounds formed in this case may cause a number of effects that take place in the clinical and physiological stage of anaphylactic shock.

Allergic diseases

Classification

According to the definition of allergy to the group of allergic diseases include such diseases, the mechanism of damaging action in which is associated with ITH, DTH or their combinations. This somewhat narrows down the usual range of allergic diseases, but from the pathogenesis point of view, this limitation is justified because it involves a very specific therapeutic, diagnostic and preventive tactic associated with the dominance of a particular damaging mechanism. It is clear that ITH, DTH, cytotoxic, immunocomplex and antireceptor damage mechanisms have different diagnostic, therapeutic and preventive priorities.

The group of ITH (IgE reagents) includes the following diseases: atopic bronchial asthma, infectious allergic bronchial asthma in children, anaphylactic shock, pollinosis, hives, swelling of Quincke, allergic rhinitis and conjunctivitis, a significant part of drug and food allergies.

The group of DTH (Tx1-reagins) includes: allergic contact dermatitis, infectious allergic bronchial asthma in adults, some forms of drug and food allergies.

General principles of diagnosis of allergic diseases

Anamnesis

Allergic diseases are among the polygenic diseases - both hereditary and environmental factors are important in their development. I.I. Balabolkin (1998) formulated it very clearly: "By the ratio of the role of environmental and hereditary factors in the pathogenesis, allergic diseases are classified as a group of diseases, the etiological factor for which is the environment, but the frequency of occurrence and severity of their course has a significant impact on the inherited predisposition.

In this regard, in the case of allergic diseases, the standard chart of the disease history is supplemented by a section "Allergological anamnesis", which can be divided into two parts:

• genealogical and family history
• hypersensitivity anamnesis (allergenic anamnesis).

Genealogical and family anamnesis

It is necessary to find out the presence of allergic diseases in the pedigree of the mother and father, as well as among family members of the patient. The following guidelines are significant for clinicians: hereditary burden on the mother in 20-70% of cases (depending on the diagnosis) is accompanied by allergic diseases; on the father's side - much less, only in 12.5-44% (I.I. Balabolkin, 1998). In families where both parents suffer from allergic diseases, the child allergy rate is 40-80%; only one parent is 20-40%; and if siblings are sick, 20-35% (L. Yeager, 1990).

Immunogenetic studies have reduced the base for hereditary predisposition to allergic diseases (atopy). The existence of a genetic system of non-specific regulation of IgE level, carried out by genes of excessive immune response by Ih- genes (immune hyperresponse), has been proved. These genes are associated with antigens of the main histocompatibility complex A1, A3, B7, B8, Dw2, Dw3 and high IgE level is associated with haplotypes A3, B7, Dw2 (Marsh D.C. et al., 1982).

There is evidence of a predisposition to specific allergic diseases, and this predisposition is supervised by different antigens of the HLA system, depending on nationality. Thus, for example, high predisposition to pollinosis in Europeans is associated with HLA-B12 antigen; in Kazakhs - with HLA-DR7; in Azerbaijanis - with HLA-B21 (I.I. Balabolkin, 1998).

At the same time, immunogenetic studies in allergic diseases cannot yet be specific guidelines for clinicians and require further development.

Allergenic anamnesis

This is a very important section of the diagnosis, as it provides information about the most possible cause of allergic disease in a particular patient. At the same time, it is the most laborious part of the anamnesis, because it is associated with a large number of various environmental factors that can act as allergens. In this connection, it seems reasonable to give a certain algorithm of interrogation based on classification of allergens.

Food allergens. Especially carefully the dependence on food allergens should be clarified in case of allergic diseases of the skin and gastrointestinal tract. You should also remember that food allergies are most common in children, especially those under 2 years of age.

"As with other allergies, in food allergies, the quality of the allergen is crucial, but in food allergens, the quantity of food allergens should not be underestimated. A precondition for the development of a reaction is that the threshold dose of an allergen is exceeded, which occurs when there is a relative excess of the product in relation to the digestive capacity of the gastrointestinal tract" (L. Yeager, 1990). This is an important thesis, because it allows to distinguish persons with various digestive disorders into the risk group and to use the correction of digestive disorders in the treatment and prevention programs for food allergy.

Almost any food product can be allergic, however, the most allergic are cow's milk, chicken eggs, seafood (cod, squid, etc.), chocolate, nuts, vegetables and fruits (tomatoes, celery, citrus), spices and spices, yeast, flour.

Recently, allergens associated with additives and preservatives, which increase the shelf life of food products manufactured abroad, have become quite widespread. If these additives were used in domestic products, they also caused an allergic reaction in people sensitive to them, and these people served as indicators of the presence of foreign impurities in domestic food. We gave this type of allergy the conventional name "patriotic allergy".

According to M. Studenikin and I. I. Balabolkin (1998), cross-allergies are possible within a single botanical family: citrus fruits (oranges, lemons, grapefruits); pumpkins (melons, cucumbers, zucchini, pumpkins); mustard (cabbage, mustard, cauliflower, Brussels sprouts); nightshade (tomatoes, potatoes); pink (strawberries, strawberries, raspberries); plums (plums, peaches, apricots, almonds), etc., are allergic to cross-allergy. You should also stop at meat products, especially poultry meat. Although these products do not have much sensitizing activity, however, in the diet of birds before slaughtering include antibiotics and they can cause allergic diseases associated with drug allergies, not food allergies. As for flour, more often the flour becomes an allergen by inhalation, rather than by mouth.

Important in the collection of this anamnesis are the indications for heat treatment, as heat treatment significantly reduces food allergenicity.

Household dust allergens. These allergens are most significant for allergic diseases of the respiratory system, in particular, bronchial asthma. The main allergens of house dust are chitin and household mite products Dermatophagoides pteronyssimus and Derm. Farinae. These ticks are common in beds, carpets, upholstered furniture, especially in old houses and old bedding. The second most important allergens of household dust are allergens of mold fungi (more often Aspergillus, Alternaria, Penicillium, Candida). These allergens are most often associated with raw, unventilated rooms and warm seasons (April to November); they are also part of the allergens of library dust. Pet allergens are the third most important allergens in this group, with cat allergens (dandruff, hair, saliva) having the greatest sensitizing effect. And finally, to domestic dust include insect allergens (chitin and cockroach excreta); daphnia, used as a dry food for fish; poultry feather (pillows and featherbeds, especially with goose feathers; parrots, canaries, etc.).

Vegetable allergens. They are primarily associated with pollinosis, and the main place here belongs to the pollen, and most often the etiological factor of pollinosis is the pollen ragweed, wormwood, swans, hemp, thymophilus, rye, plantain, birch, alder, poplar, nut. According to M.Y. Studenikin and I.I. Balabolkin (1998), common antigenic properties (cross-allergy) are pollen from cereals, mallow, wormwood, ragweed, sunflower; pollen from birch, alder, hazelnut, poplar, aspen. These authors also note the antigenic relationship between birch pollen, cereals and apples.

Insect allergens. The most dangerous insect poisons (bees, wasps, hornets, red ants). However, often allergic diseases are associated with saliva, excrements and secrets of the protective glands of blood-sucking insects (mosquitoes, gnomes, gadflies, flies). More often, allergic diseases associated with these allergens are realized in the form of skin manifestations; however, (especially bee venom, wasp, hornet, ants) can cause severe conditions (swelling Quincke, severe bronchospasm, etc.), up to anaphylactic shock and death.

Medicinal allergens. Anamnesis should be collected very carefully in this direction, because it is not only a diagnosis of an allergic disease, but, above all, it is a prevention of possible death due to the unexpected development of anaphylactic shock. I think it is not necessary to convince that this type of allergic anamnesis should become a mandatory tool for all clinicians, because there are well known cases of anaphylactic shock and lethal outcomes with the introduction of novocaine, X-ray contrast substances, etc., which are not only diagnosed as an allergy disease, but also as a prevention of a possible lethal outcome due to the unexpected development of anaphylactic shock.

Inasmuch as medicines, as a rule, are relatively simple chemical compounds, they act as haptens, joining with proteins of organism up to complete antigen. In this regard, drug allergenicity depends on a number of conditions: 1) ability of drug or its metabolites to conjugate with protein, 2) formation of strong connection (conjugate) with protein, the consequence of which is the formation of complete antigen. Very rarely unchanged drug can form a strong bond with protein, more often it is associated with metabolites as a result of drug biotransformation. This fact determines a fairly frequent cross-sensitization of drugs. LV. Luss (1999) presents such data: penicillin gives cross-reactions with all drugs of penicillin series, cephalosporins, sultamicillin, sodium nucleinate, enzyme preparations, a number of food products (mushrooms, yeast and yeast-based products, kefir, kvass, champagne); sulfonamides cross-react with novocaine, ultracaine, anesthesia, antidiabetic drugs (antidiabetics, antibet, diabetes), triampur, para-aminobenzoic acid; analgine cross-reacts with non-steroidal anti-inflammatory drugs, derivatives of acetylsalicylic acid and salicylates, food containing tartrazine, etc.). In this regard, another circumstance is important. The simultaneous administration of two or more drugs may have a mutual effect on the metabolism of each of them, violating it. Violation of the metabolism of drugs that do not have sensitization properties may cause allergic reactions to them. L. Yeager (1990) makes this observation: the use of antihistamines in some patients caused allergic reactions in the form of agranulocytosis. Thorough analysis of these cases revealed that these patients simultaneously took medicines that violated the metabolism of antihistamines. Thus, it is one of the strong arguments against polypragmatism and a reason to find out in the allergic anamnesis the mutual influence on metabolism of used drugs. I am deeply convinced that in modern conditions for the prevention of allergic diseases, a doctor should know not only the names of drugs, indications and contraindications, but also know the pharmacodynamics and their biotransformation.

Quite often, the use of drugs is associated with the development of effects, which Ado identified in a separate group called pseudoallergies or false allergies. As has already been shown, the fundamental difference between pseudo allergy and allergy is the absence of pre-sensitization associated with antibodies-reagents (IgE). The clinical effects of pseudoallergies are based on the interaction of chemicals either directly with the membranes of fat cells and basophils, or with the receptors of cells to IgE, which ultimately leads to degranulation and release of BAS, primarily histamine with all its consequences.

It seems important to provide clinical guidelines that allow for differential diagnosis of drug allergies and pseudoallergies. Pseudoallergy more often occurs in women after 40 years of age on the background of diseases that violate the metabolism of histamine or sensitivity of receptors to BAS (pathology of the liver and biliary tract, gastrointestinal tract, neuroendocrine system). The background for the development of pseudo-allergy is also polypragmatism, oral administration of drugs in case of ulcer, erosive, hemorrhagic processes in the gastrointestinal mucosa; the drug dose does not correspond to the age or weight of the patient, inadequate therapy for the current disease, changes in pH environment and temperature of solutions administered parenterally, simultaneous administration of incompatible drugs (L.V. Luss, 1999). Typical clinical signs of pseudoallergies are: the development of the effect after the primary administration of the drug, the dependence of the severity of clinical manifestations on the dose and method of administration, a fairly frequent absence of clinical manifestations at repeated administration of the same drug, the absence of eosinophilia.

In conclusion of the section on drug allergens, we present a list of drugs that most often provoke the development of allergic diseases. This list is compiled on the basis of data provided in the works of L. V. Luss (1999) and T. I. Grishina (1998) used the principle from more to less: analgin, penicillin, amidopirin, sulfonamides, ampicillin, naprosen, brufen, ampiox, aminoglycosides, novocaine, acetylsalicylic acid, lidocaine, multivitamins, X-ray-contrast drugs, tetracyclines.

Chemical allergens. The mechanism of sensitization with chemical allergens is similar to medicinal allergens. The most common allergens are caused by the following chemical compounds: salts of nickel, chromium, cobalt, manganese, beryllium; ethylenediamine, products of rubber, chemical fibers, photoreagents, toxic chemicals; detergents, varnishes, paints, cosmetics.

Bacterial allergens. The question of bacterial allergens arises in the so-called infectious allergic pathology of the mucous membranes of the respiratory and gastrointestinal tract and, above all, in infectious allergic bronchial asthma. Traditionally, bacterial allergens are subdivided into allergens of infectious pathogens and allergens of opportunistic bacteria. At the same time, according to V. N. Fedoseeva (1999) "there is a certain conditionality in the terms of pathogenic and non-pathogenic microbe. The concept of pathogenicity should include a wider range of properties, including allergenic activity of the strain". This is a very principled and correct position, because it is well known diseases in which the allergic component plays a leading role in the pathogenesis: tuberculosis, brucellosis, mug and others. This approach makes it possible to fill with concrete meaning the concept of conditionally pathogenic microbes, which are inhabitants of mucous membranes (streptococci, neisserias, staphylococcus, Escherichia coli, etc.).

These microbes under certain conditions (genetic predisposition, immune, endocrine, regulatory, metabolic disorders; exposure to adverse environmental factors, etc.) may acquire allergenic properties and cause allergic diseases. In this regard, V. N. Fedoseeva (1999) emphasizes that "bacterial allergy plays a critical role in the etiopathogenesis of not only particularly dangerous infections, but primarily in focal respiratory diseases, gastrointestinal pathologies, skin".

Previously, bacterial allergy was associated with delayed hypersensitivity, because a high allergic activity of nucleoprotein microbial cell fractions was detected. However, back in the 40s Swineford O. and Holman J. J. (1949) showed that polysaccharide fractions of microbes can cause typical IgE-dependent allergic reactions. Thus, bacterial allergy is characterized by a combination of delayed and immediate types of reactions, and this was the basis for the inclusion of specific immunotherapy (SIT) in the complex treatment of bacterial allergy diseases. At present, "non-serial" bronchial asthma, "staphylococcal" infectious allergic rhinitis, etc. are distinguished. Practitioners should know that it is not enough to establish the infectious allergic nature of the disease (eg, bronchial asthma), it is necessary to decipher also what kind of conditionally pathogenic flora determines allergization. Only then, by using the SIT treatment with this allergy vaccine, a good therapeutic effect can be obtained.

At present, a significant role of dysbacteriosis in the formation of immunodeficiencies and immune insufficiency has been established. From our point of view, mucous membrane dysbiosis is also a significant factor in the etiopathogenesis of allergic diseases. Clinicians should have in their hands not only methods to assess intestinal dysbiosis, but also methods to assess the norm and dysbiosis of other mucosa, in particular, the respiratory tract.

The most common etiopathogenetic factors of infectious diseases of allergic nature are: hemolytic and green streptococci, staphylococci, catarrhal microococci, Escherichia coli, synergic bacillus, proteins, nonpathogenic neisseries.

Complaints

In this section we found it necessary to fix attention on the most typical subjective sensations that orient the doctor to the possibility of allergic diseases and give rise to the diagnostic process in this direction.

First of all, it should be noted that these subjective sensations appear either in a perfectly healthy person, or, if the patient, can not be explained by the features of the existing pathology.

These subjective feelings can be general and local in nature.

General manifestations: chills, fever, excitement, weakness, dizziness, migraine like syndrome, pale skin, low blood pressure, itching, burning, sneezing, increased lymph nodes.

Local manifestations. Most often they are manifested by complaints from the skin, gastrointestinal tract, mucous nasopharynx, bronchial tree, mouth, joints.

Skin manifestations: redness and dry cheeks, itching, burning, photosensitivity, sensitivity to cold, skin rashes (erythema, papules, blisters, spotty-papule rashes, maculopaulean rashes, korepine-like, scarlet-like, etc.). Rashes often merge in the form of a variety of garlands, sharply separated from normal skin (excluding allergic dermatitis), oedema sometimes bullous. Allergic papula, unlike the infectious one, has a slightly purple cyanotic tint. Hyperemia zones rise above the surface of the skin, have an oval shape. All skin rashes are most often accompanied by itching and burning, but not necessarily. In a typical case, this resembles a nettle burn.

Complaints from the gastrointestinal tract: flatulence, abdominal pain and burning, unstable or frequent liquid stools, constipation, nausea, vomiting, gastric or intestinal colic, reactive pancreatitis.

Eye symptomatology: the feeling of a foreign body in the eye, itching, burning, tears, swelling of the eyelid, dermatitis eyelid, blepharitis, conjunctivitis, keratitis, uveitis, sclerite, etc.

Symptoms from the mucous membrane of the nasopharynx, bronchial tree and mouth: sore throat, itching, burning, sneezing, coughing or dry coughing, abundant watery and often foamy discharge from the nose, swelling of the nasopharynx, nasopharyngeal gland; difficulty breathing, bronchospasm, geographical tongue (a reliable sign of allergic disease).

Pain in the joints and muscles is quite an alarming symptom, as it indicates a systemic allergic disease. Quite often, these complaints are found in drug and food allergies.

Clinical Picture

First of all, it should be noted that the clinical picture of immediate hypersensitivity (ITH) distinguishes between two phases - early and late.

The early phase is clinically evident a few minutes (up to 30 minutes) after contact with the allergen and also stops rapidly (not more than an hour). At the heart of this phase, the ITH mechanisms described above are related to the release of BAS and the development of pathophysiological disorders (vasodilatation, increased permeability, swelling, mucus hyperproduction, smooth muscle spasm), which are clinically manifested by erythema, intestinal colic, bronchospasm, swelling, blisters, mucosa detachment, itching, burning, etc.

Late phase begins in 2-6 hours and lasts 1-2 days. At the heart of this phase, the so-called "allergic inflammation", where the main protagonists are neutrophils and eosinophils, infiltrating the lesion site, producing proteolytic enzymes (extracellular cytolysis) under the influence of which are formed kinins, activated complement system with the formation of anaphylotoxins, activated blood clotting system, violated its aggregation state (microcirculation). The production of cytokines by activated fat cells and migrant leukocytes (IL-1, IL-6, FNO-Alpha, chemokines, GM-CSF) promotes leukocyte infiltration and supports inflammation (A. A. Yarilin, 1999).

From the point of view of classical mechanisms of inflammation, if the early phase of allergic reactions can be characterized as exudative-destructive, then the late phase - as productive-destructive.

From the clinical point of view, allergic diseases are to a greater extent functional disorders. Organic (structural) changes are formed only in the long chronic course with frequent relapses. The diagnosis of allergic diseases is mainly based on complaints, anamnesis and paraclinical studies. However, as with any nosology, objective criteria for diagnosis also occur in allergic diseases.

Conditionally, allergic diseases can be divided into systemic and local.

The main place of localization of fat cells are serous membranes, spleen, epithelium and submucosal layers of the gastrointestinal, respiratory and urogenital tract; skin, connective tissue of capillary clutches. If the clinical symptomatology in allergic disease comes from several locations of the localization of fat cells, it is said about a systemic allergic disease. Clinically, this is manifested by symptoms in various combinations on the side of the nasopharynx, skin, gastrointestinal tract and others. In local allergic diseases, clinical symptomatology comes only from individual loci of fixation of fat cells (rhinitis, conjunctivitis, hives, gastritis, etc.).

The exception is clinical symptomatology coming from the place of localization of mast cells in the connective tissue of capillary clutches. It is always a systemic allergic disease, because it is based on vasculitis, in maximum expression manifested by anaphylactic shock.

Apart from anaphylactic shock, there is no point in classifying some or other allergic diseases as systemic or local, because it is purely a conditional division, and each doctor makes such a differentiation in each case. This differentiation is necessary for the clinician to evaluate the prevalence and severity of the course of the pathological process and the correct construction of treatment tactics based on this evaluation.

The literature contains data on the favorite localization of certain allergens. For example, food allergies are gastrointestinal tract and skin; drug allergies are skin and systemic manifestations; insecticide allergies are more common systemic manifestations (anaphylactic shock).

However, let us return to objective data. Very often the first signs of an allergic disease are changes in the skin, most of which are already described in the section "Complaints". It should be added that the pallor of the skin is especially alarming in the presence of clinical signs of allergy, reflecting a violation of tissue perfusion, which is the basis of anaphylactic shock.

Unsurprising objective signs of allergic diseases are hyperemia of eyelids and edema of their skin, edema and hyperemia of conjunctiva, eyeballs.

Almost obligatory objective signs of allergic diseases are edema and swelling of mucous membranes; and also serous or foamy secretions (more often from the nose). Mucous membrane changes in allergic diseases are quite typical: mucous membrane edema, swollen with a marble hue, often cyanotic, swelling of the hind throat, tongue, posterior pharyngeal wall with multiple congestions of lymphatic tissue. The mucous membranes of the lower and middle nasal sinuses are characterized by white spots (Voyachek spots). It is important to remember that in the first year of life there can be no hypertrophy of adenoids - their increase in this period is a consequence of swelling accompanying allergic diseases. Once again, attention should be fixed on the "geographical" language - a reliable sign of allergic diseases.

Objective signs from the bronchopulmonary system: more often dry sometimes small and medium-bubble wheezing, a slight boxy tinge of percussion sound.

On palpation of the abdominal cavity more often pain in the upper half of the abdomen, spasmed jejunum, because gastrointestinal allergies are more often manifested by imunite, duodenitis, gastritis, bulbit, esophagitis.

Reduced blood pressure, tachycardia, high body temperature are also frequent objective manifestations of allergic diseases.

It should be stressed once again that these clinical signs are important in the diagnosis of allergic diseases only when they appear in healthy individuals or when these clinical signs can not be explained by the disease.

It should be remembered that the clinical picture of allergic diseases is very diverse and is not limited to the given clinical data, but all clinical signs are based on the release of BAS, swelling, increased secretion, spastic contraction of cavity structures (intestines, bronchi, blood vessels, bile and urinary tract). The combination of these pathogenetic moments and determines the features of the clinical picture of allergic diseases and the variety of their nosological forms. In this regard, we found it possible not to give a detailed description of the nosological forms included in the group of allergic diseases, except for those that can be considered as urgent conditions: anaphylactic shock, Lyell syndrome, Stevens-Johnson syndrome, swelling Quinke, asthmatic status.

Anaphylactic shock

We should emphasize the urgency of diagnosis and emergency shock relief. "In essence, the terminal period of any serious illness is accompanied by local or widespread hemodynamic disorders in the microcirculation system, so there is a natural tendency to consider shock as one of the variants of the terminal state" (N.K.Permyakov, 1979). A well-known intensive care physician G.A. Ryabov (1979) believes that "shock is a syndrome characterized by a critical decrease in blood flow in tissues".

In the process of dying, two stages are distinguished: 1) initial reversible period - prevalence of compensatory and adaptive changes over pathological ones; 2) irreversible period - prevalence of pathological changes. The compensatory reactions are based on an attempt to prevent irreversible damage to the central nervous system (CNS) by available means. This is primarily due to the resulting centralization of blood circulation. Closing the blood flow in the heart-pulmonary-brain triangle significantly increases the oxygenation of the CNS. It is this mechanism - vasoconstriction of the periphery also lies at the heart of shock. Prolonged peripheral vasoconstriction leads to tissue transition instead of highly effective oxidative phosphorylation to less effective, but temporarily compensating energy deficiency anaerobic glycolysis, which eventually ends with severe metabolic acidosis, which is the basis of the next, irreversible dying period.

Thus, the shock of any etiology, and especially anaphylactic shock, is a sudden transition from life to the initial period of dying. It is the urgency of diagnosis and emergency assistance in case of shock that guarantees a return to life, and in their absence, the shock ends with the obligatory transition to an irreversible stage of dying.

So, shock is an emergency condition, based on peripheral vasoconstriction with subsequent vasodilation, a sharp decrease in tissue blood flow, metabolic disorders. However, the causes of these disorders may be different (bleeding, dehydration, toxins, trauma, acute heart failure, BAS in allergies, etc.). In this regard, the clinical picture of shock is quite typical for different types of shock, but the effectiveness of treatment (especially in the early stages) is directly related to determining the cause of shock, because neutralization of the causal factor can completely block the development of further stages of shock.

Since the time of N.I. Pirogov, in the clinical picture of shock there are two phases: erectile and torpid.

The erectile phase of shock, which lasts 20-30 minutes, manifests itself as two syndromes - cerebral and cardio-vascular (A. Monov, 1982). Cerebral syndrome manifests itself as excitation, euphoria, increased reflexes, hypersensitivity, and dilation of pupils. The patient in consciousness is excited, anxious, reacts to any touch. Cardiovascular syndrome is characterized by normal or elevated A.D., tachycardia or slow pulse; pale, less often hyperemia of the skin, face.

The torpid phase marks the attachment of all major pathogenetic mechanisms of shock (true shock), lasts several hours and ends lethally with no external help. In the torpid phase, three degrees of shock are distinguished (V.I. Pokrovsky, 1976; A. Monov, 1982).

The shock of the first degree, compensated, is dominated by vasoconstriction: severe general condition, pallor, cyanosis of lips and nail phalanges, superficial breathing, signs of hypothermia. CNS symptoms: weakness, slow response, constricted pupils. Cardiovascular manifestations: slightly reduced or normal A.D., slow pulse.

Shock of II degree, subcompensated, vasodilation dominates: very severe condition, cyanosis (spilled cyanosis) is growing, breathing is frequent, hypothermia, strong thirst, oligoanuria. Cerebral syndrome: retardation, slight blurring of consciousness, dilation of pupils with slow reaction to light. Cardiovascular syndrome: heart deafness, hypotension (systolic A.D. 80-60 mm Hg column), tachycardia (over 100 beats per minute), extrasystole, pulse is poorly palpable, sleeping peripheral veins. Metabolic acidosis, hypokalemia, hypoxia in blood.

Degree III shock, decompensated, vasoatonia dominates: extremely severe condition, total cyanosis, hypothermia, superficial respiration, frequent Cheyne-Stokes type, anuria. Cerebral syndrome: no consciousness, complete adynamy, pupils wide open to light do not respond, loss of sensitivity. Cardiovascular syndrome: undefined or thready pulse, systolic A.D. below 50 mm Hg, deaf heart tones, arrhythmia. There is a pronounced metabolic acidosis in the blood, severe hypoxemia and, as a result, their - secondary irreversible changes in tissues and organs.

Allgover's criterion - the ratio between pulse rate and systolic A.D. In the norm, Allgover's criterion is 0.5; in case of shock of the first degree - up to 1.0; II degree - from 1.0 to 1.5; III degree - above 1.5.

As can be seen from the above clinical picture, shock is a dynamic process that necessarily leads to death without effective external assistance. This aid is most effective in the early stages of shock development (erectile phase and first degree of torpid phase). The basis of effective shock relief, in addition to its impact on the main pathogenetic links, is to identify and eliminate the cause of shock. In this regard, it seems reasonable to characterize the main differences between anaphylactic shock and other types of shock.

First of all, it should be remembered that anaphylactic shock most often develops in virtually healthy individuals or in remission of chronic disease. The other types of shock are often the result of exacerbation of chronic or acute pathology (bleeding, dehydration, intoxication, trauma, acute heart failure, stroke, thyroid, adrenal gland, pancreas, etc.).

In principle, any allergen with any route of entry can cause anaphylactic shock, but more often it is insect bites and parenteral administration of drugs. Given the current situation in our society, meaning the uncontrolled and often unreasonable use of drugs, which can be characterized by the term "drug intervention", the vast majority of cases of anaphylactic shock are associated with drugs.

In this regard, meticulous and carefully collected allergological anamnesis in each patient to whom it is supposed to prescribe drugs, especially parenteral administration of drugs, is a prerequisite for the treatment process and an effective means of preventing anaphylactic shock. At the same time, it should be taken into account that sensitization to drugs may be associated not only with taking them, but also with the mother's intake of these drugs when breastfeeding and inhaling aerosols of drugs (visiting medical facilities, being in the vicinity of pharmaceutical enterprises).

In case of parenteral administration of medicines, the shock develops immediately after the injection or a few minutes after it. It may be a lightning-fast variant that ends lethally within the first minute after injection.

In case of oral administration of drugs or skin application, the shock develops within a few hours, sometimes even within a day after the injection.

Anaphylactic shock usually begins with the prodromal period, which, with the care of medical personnel, can be fixed and quickly eliminated. This is primarily chills, numbness in the extremities, swelling at the place of administration or on mucous membranes, the appearance of rashes or hyperemia. The prodromal period can be very short (parenteral administration) or long (oral administration or skin application), but you should always know and look for its manifestations, because this is the stage of shock, which is quickly, effectively and without consequences for the patient. If the prodromal period is missed, the further clinical picture of anaphylactic shock corresponds to the above described phases and stages.

However, this classic picture of anaphylactic shock has a characteristic coloring associated with the fact that anaphylactic shock is an allergic disease. Allergies in anaphylactic shock include: itching of the skin (especially the palms), mucous membranes or conjunctiva; laryngeal edema, angioedema; manifestations of the type of hives or other types of rash. Rather typical are the erythema-urtical complex, which is a reddened skin area with a centrally located bladder or vesicles and flour-edematous syndrome, manifested by redness, increased secretion, swelling and itching of various mucous membranes: conjunctivae, oral cavity, anal opening, genitals, urethra, and others. (A. Monov, 1982). Allergic manifestations of late type in anaphylactic shock are manifested by hemorrhagic-petechial or erythemic-infiltration changes in the skin, increased lymph nodes, joint syndrome (A. S. Smetnev, L. I. Petrova, 1977; A. Monov, 1982).

Lyella syndrome

This is the most severe version of drug allergic skin lesions with the development of necrolysis of all layers of the epidermis and its detachment. It is at the heart of DTH disease, but often ITH. Lyell syndrome is most often associated with sulfonamides, tetracyclines (vibramycin, morphocycline, rondomycin), levomycethin, pyrazolone derivatives (butadione, amidopirin, analgin), barbiturates, oxycam (pyroxycam, xefocam, thomimine). Especially dangerous are combinations of antibiotics and sulfonamides, as well as long or frequent prescription of non-steroidal anti-inflammatory drugs.

More often, clinical manifestations develop 10-14 days after starting medication (DTH), but may also occur within the first hours (ITH). The disease begins acutely with high fever, acute weakness, adynamy, and often sore throat. Against this background, within a few hours, large, sharply painful erythematous spots appear on the skin, which have a cyanide tint. During the next few hours or the first two days, erythematous areas are transformed into bubbles with damage to all layers of the epidermis. The epidermis is peeled off and extensive erosive surfaces are formed from which serous hemorrhagic fluid is released. The process spreads rapidly and the epidermis can peel off almost the entire surface of the skin, except the scalp. Similar changes occur in the mucous membranes of the mouth, throat, larynx, eyes, genitals and often throughout the gastrointestinal mucosa with the formation of erosions and ulcers. Typical for Lyell syndrome is that the lesion of the mucous membranes precedes skin necrosis. The clinical picture is very similar to the II-III degree burns. Such an extensive skin and mucous membrane lesion determines the overall very serious condition of the patient and is reminiscent of the ancient type of execution, when a living person was skinned. Patient with Lyell syndrome is practically deprived of the main protective barriers - skin and mucous membranes. The following factors determine the severity of the general condition: 1) expressed pain syndrome, 2) acute intoxication, 3) significant water-electrolyte balance disorders and CBD, 4) development of thrombo-hemorrhagicolgo syndrome, 5) hemodynamics and microcirculation disorders, 6) acute hypoproteinemia, 7) frequent addition of sepsis. In their aggregate, these factors quite rapidly lead to the development of lesions of the liver, kidneys, myocardium, CNS with subsequent development of acute renal failure, hepatic failure, coma. An additional factor aggravating the patient's condition is difficulty in breathing and malnutrition due to lesions of the mucous membranes.

A significant aid to the differential diagnosis of Lyell syndrome from other similar diseases, in addition to the severity of the condition is a symptom of Nikolsky, which is sharply positive in Lyell syndrome: when pulling the tweezers on the bubble wall there is a peeling of the epidermis beyond the borders of the bubble (degree I); if you rub the skin between two bubbles, there is an erosion (degree II); if you rub the skin in a place where there are no rashes, there is an erosion (degree III). Most often, Lyell syndrome has to be differentiated with Stevens-Johnson syndrome and 'staphylococcal burned skin syndrome'. Characterization of the syndrome

Stephens-Johnson will be listed below. Regarding the "staphylococcal burned skin syndrome" or superficial staphylococcal epidermolysis, it is characterized by the development of necrosis of only the superficial layer of the epidermis, a negative symptom of Nikolsky and much less severe condition of the patient.

Stevens-Johnson syndrome

Characterized as an inflammatory febrile illness with predominant lesions of the skin and mucous membranes.

Most of it is a drug allergy to sulfonamides, antibiotics tetracycline, levomycetin, non-steroidal anti-inflammatory drugs; however, there is evidence that the cause of Stevens-Johnson syndrome may be a viral and mycoplasma infection. Skin lesions, unlike Lyell syndrome, are never accompanied by lesions of all skin layers. More often, bubble formation is associated with intraepidermal keratocyte adhesion disorder (intraepidermal bladders) or adhesion disorder between epidermis and dermis due to dermal lesions (subepidermal bladders).

Stevens-Johnson syndrome begins as an acute infectious disease: weakness, lack of appetite, headaches, high (40-41C) fever of the constant type. Starting from the 4th-5th day of the disease there are changes in the mucous membranes, then with a short break or at the same time changes in the skin. Changes in the mucous membranes begin with the mouth (aphthous stomatitis), then the eye, nasal cavity, urethra, gastrointestinal tract. Blisters appear on the mucous membranes, which quickly open with the formation of extensive sharply painful erosions and ulcers. Damage to the mucous membrane of the eye can lead to corneal rupture and blindness. Following the lesion of the mucous membranes or at the same time with it there are changes in the skin: on the face, occiput, forearms, shins, torso, pubis, external genitalia appear extensive painful erythematous areas, in place of which a few hours later formed bubbles and large bubbles, which quickly open with the formation of erosions and ulcers. Characteristic of the lesion of the palms and soles - erythema with hemorrhagic component. Bronchitis and aspiration pneumonia are the most common complications. SCE is often normal, however, the shift of the leukocyte formula to the left is typical.

The clinical picture is very similar to Lyell's syndrome, however, the disease proceeds more easily, without the involvement of parenchymatous organs and is often resolved independently after 10-14 days. The main difference from Lyell's syndrome is a negative symptom of Nikolsky.

Quinque edema (angioedema)

There are several variants of angioedema: allergic - based on ITH; pseudoallergic - due to histamine-releasing drugs and hereditary angioedema associated with C1q inhibitor failure, which leads to activation of C4 and C2 components of the complement, the formation of a kininine-like factor, increased vascular permeability and the development of angioedema. In all three variants of angioedema, the pathogenesis is similar and associated with dilatation and increased vascular permeability of deep dermis and submucosa.

The clinical picture is quite typical and is manifested by the sudden development of marked local edema in any part of the body. Oedema develops more often on the face, extremities, external genitalia. Characteristically acute dough swelling, a sense of numbness, often a moderate itching. The skin in place edema is densely elastic to the touch, white, sometimes pinkish. Nausea, vomiting, diarrhea and headache are often observed. After the disappearance of acute phenomena - polyuria.

Especially dangerous is swelling of the larynx, which can lead to asphyxia and the need for intubation or tracheotomy. Swelling of the larynx is a risk factor for laryngeal edema, because at this localization swelling quickly covers the tongue, mucous cheek, epiglottis, larynx, vocal cords and glandular space. The clinical picture of edema of the larynx: the sudden appearance of painful throat cramps, pain in swallowing, a feeling of difficulty when breathing, rough cough often continuous with hemoptysis, a husky voice, face cyanosis, swelling of cervical veins. Particularly dangerous is diffuse swelling of the larynx or local edema of the vocal cords and glandular space. In laryngoscopy - diffuse hyperemia and oedema of the entire larynx mucosa (diffuse form), or edema of yellow-gray blisters (local form). Voice ligaments resemble thick translucent yellowish rolls (A. S. Smetnev, L. I. Petrova, 1977). In a heavy current, swelling increases rapidly, it is difficult not only to breathe, but also to exhale; the sound of a saw resembling strictronic breathing, conducted into the lungs and listened to at auscultation; diffuse cyanosis, in breathing involved auxiliary muscles, tachycardia, lowering blood pressure, the patient rushes in bed, possible seizures, consciousness disorders and coma. In the light current - a rapid reverse development, leaving for a short time a feeling of discomfort in breathing and the strength of the voice. The main distinguishing feature of the swelling of the Queen's larynx from other similar conditions (diphtheria, foreign body, laryngeal tumor, etc.) is the presence of allergic anamnesis, a sudden onset more often against the background of other clinical manifestations of allergy (hives), great dynamism, a tendency to relapse, the emergence of similar attacks or other allergic reactions in the past in the patient or his family.

Asthmatic status

Asthmatic status (AS) - conditions of severe asphyxia due to a prolonged attack of bronchial asthma (BA), which is not purchased by conventional bronchodilators for the patient within a day.

The trigger mechanism for AS is the blockade of beta-adrenergic receptors due to frequent exacerbations of BA due to massive effects of allergens, inflammatory processes of the bronchopulmonary system, psycho-emotional stress, unjustified or rapid abolition of glucocorticosteroids, frequent and uncontrolled use of sympathomimetics (adrenomimetics). It is important to remember that in the process of its degradation, simatomimetics may accumulate in the form of intermediate products that do not stimulate but block beta-adrenor receptors and lead to their bronchospastic rather than bronchodilating effect. Frequent use of derivatives of purines - methylxantans (euphylline, theophylline, etc.) may also lead to the development of resistance to them and AC, but there is no blockage of beta-adrenergic receptors, because the mechanism of their action is connected with the inhibition of phosphodiesterase and accumulation in tissues of cAMF. The accumulation of cAMF inhibits the ability of myosin to combine with actin, resulting in a decrease in the contractile activity of smooth muscles and the relaxation of bronchi.

Bronchospasm, which is not eliminated for a long time, leads to a sharp violation of bronchial drainage function and obstruction due to edema, inflammation, dyskinesia of small airways and clogging them with viscous sputum.

Thus, the main difference between the attack of BA and AS is that its basis is not bronchospasm, but swelling of mucous bronchiol and mechanical closure of their viscous secret. An additional component of bronchoobstruction is expiratory airway closure: when inhaled, bronchi expand slightly, letting more air into the lungs than the patient can exhale through the airways clogged with viscous sputum; the patient tries to make an active exhalation by straining the exhalation muscles, the intrathoracic pressure increases, and bronchi are squeezed even more (A.P. Silber, 1984). It should also be noted that the more difficult an exhalation is due to high chest pressure and the more active the patient attempts to exhale, the greater the likelihood that the mucous trachea and large bronchi will detach from the cartilage, protrude it into the airway, and develop expiratory stenosis, which dramatically increases respiratory depression (A.P. Silber, 1984). Against this background, right ventricular insufficiency is necessarily associated, because the right ventricle has to overcome high intra-thoracic pressure.

The main pathogenetic components of AS are: betaadrenoreceptor blockage or resistance to purine derivatives, airway obstruction, right ventricular insufficiency, combined hypoxia, metabolic disorders.

Depending on the adherence or degree of severity of these pathogenetic components, three stages are distinguished in the clinical picture of AS (A. S. Smetnev, L. I. Petrova, 1977; A. A. Bunatyan, G. A. Ryabov, A. Z. Manevich, 1977; A. G. Chuchalin, A. V. Tretyakov, 1997, etc.):

The first stage (relative compensation). It is based on bronchoconstriction associated with the blockade of beta-adrenor receptors or resistance to purine derivatives and the beginning of the formation of respiratory obstruction. The main thing in the clinical picture is: acute respiratory insufficiency, which is not compensated by bronchodilators usual for the patient; mismatch between the small amount and audible rattles heard at auscultation and a large number of pronounced and audible rattles heard from a distance; absence of sputum; difficulty in breathing and, most importantly, exhalation. The clinical picture of the first stage of loudspeakers is typical: anxiety, fear, shortness of breath (over 60 per minute), pale cyanosis, pulmonary emphysema, relative cardiac stupidity is not determined, cardiac tones are deaf, accent and splitting of the second tone over the pulmonary artery, tachycardia (over 100 beats per minute), moderate increase in BP, contraction of abdominal press muscles and swelling of cervical veins when exhaled; retraction of the intercostal spaces, jugular loin, tension of the sterno-clavicular-associated muscles, mouth movement, breathing air; time of forced exhalation is more than 10 seconds. Blood hypoxemia, hypokapnia, respiratory alkalosis, polycitemia.

The second stage (decompensation). It is based on airway obstruction, acute right ventricular heart failure, combined hypoxia, metabolic disorders. The main thing in the clinical picture is: "mute lung" (wheezing won't listen, breathing noises are sharply weakened), practical absence of breathing tour of the chest, absence of sputum. For a clinical picture of the second stage of AS is characteristic: the patient can not say a few words in a row without translating breath, breathing superficial, very frequent, the chest is in a state of maximum deep breath with a subtle inflow of intercostal spaces and the absence of visible breathing tours, spilled pale cyanosis, tachycardia, weak filling or thread pulse, low blood pressure, deaf heart tones, extrasystole. On the electrocardiogram signs of right atrium and right ventricle overload, diffuse changes in myocardium. Blood polycythemia, pronounced hypoxemia, mixed (respiratory and metabolic) acidosis.

The third stage (hypoxic coma). It is based on combined hypoxia, metabolic disorders (respiratory and metabolic acidosis, hypohydration, adrenal insufficiency). The main thing in the clinical picture is consciousness disorder. The clinical picture of the third stage of AS is characterized by: motor anxiety, often seizures and then loss of consciousness, disappearance of reflexes, diffuse cyanosis, tachypnea, bradypnea, "silent lung", pulse is not palpable, BP is not determined.

Diagnosis of allergic diseases

There are three areas in the diagnosis of allergic diseases

• Nosological diagnosis, or clinical identification of an allergic disease;
• pathogenetic diagnosis, or identification of specific ITH or DTH features;
• etiological diagnostics, or identification of a causal factor of ITH or DTH.

Nosological diagnostics

As for nosological diagnostics, this issue has already been discussed in previous sections. It should only be emphasized that in the overwhelming majority of cases it is purely clinical diagnostics, however, clinical data, as a rule, are not enough for correct and effective therapy and, especially, for the prevention of relapse of the disease, because even island allergic diseases are a chronic process that can be repeated in years, and therefore diagnosis of pathogenetic features of a particular disease in a particular patient and finding out the causal factors only in the aggregate can provide a basis for the efficacy of this treatment.

Of particular importance in clinical practice for all nosological forms is the identification of risk groups for these diseases. This is significant, first of all, for allergic diseases, because it is in the risk group that the question of drug therapy, especially related to parenteral manipulations due to the possibility of development of the described urgent conditions (anaphylactic shock, swelling of Quinke, etc.) should be addressed very carefully. Currently, the problem of identifying risk groups for allergic diseases has not been adequately developed and clinical guidelines for identifying risk groups are rather scarce:

1. genealogical anamnesis;
2. family anamnesis;
3. neonatal pathology.

As for genealogical and family anamnesis - they are described in the section of allergic anamnesis. With regard to neonatal pathology, in principle all these children can be classified as a risk group for allergic diseases, but most often allergic diseases develop in children who have suffered from birth trauma (48%) and asphyxia (45%).

Pathogenetic diagnostics

First of all, it should be noted that all tests used in pathogenetic diagnostics of ITH or DTH have no independent diagnostic value, because diagnosis of allergic diseases is a purely clinical diagnostics, but they are a significant aid in differential diagnostics with other clinically similar pathologies, and can also serve as criteria for identifying risk groups in healthy individuals. However, the most important pathogenetic diagnostics tests are for the development of an effective therapy program, because they orient the doctor in those dominant disorders that are relevant to the patient at the moment. Especially important is pathogenetic diagnostics in the period between relapses, as it allows to form a reasonable program of prevention of exacerbation.

There are two directions in pathogenetic diagnostics: 1) immunological and 2) biochemical or pathochemical. These diagnostic directions reflect the stages of pathogenesis of allergic diseases, which was formulated by A. D. Ado in his time.

Immunological pathogenetic diagnostics

To date, for diagnostics and differential diagnostics of ITH and DTH we can offer the following indicators: eosinophils, monocytes, basophils, CD4, CD8, CD20, CD23, IgA, IgE, IgG, IL-2, IL-4, IL-5, IL-12, interferon-gamma (IFGamma), alpha tumor necrosis factor (FNO-Alpha), FNO Beta or lymphotoxin.

Without going into the methodological details of determining these indicators, which are well known to laboratory immunologists, we consider it appropriate to give a brief clinical description of each of these indicators in the diagnosis of ITH and DTH, options for comprehensive assessment in the diagnosis of allergic diseases and the possibility of differential diagnosis of ITH and DTH.

Eosinophils. Eosinophilia is a reliable indicator of ITH. Eosinophilia is distinguished by small (up to 10%), moderate (up to 20%) and pronounced (more than 20%) eosinophilia. Small and moderate eosinophilia usually accompany the damaging orientation of the ITH; pronounced eosinophilia is a protective (parasitic invasion).

Basophils. These cells receive undeservedly little attention compared to their tissue counterparts by mast cells. However, the presence on their surface of high- and low-affinity receptors for IgE and inside their basophilic granules containing large amounts of BAS, including histamine, allows us to classify them as the main cells participating in ITH. The presence of basophilia, especially in combination with eosinophilia, is a clear indication in favor of ITH.

Monocytes. Mononuclear phagocytes (macrophages) undergo three stages of development: bone marrow (monoblast, promotional); circulating (monocyte) and tissue (macrophage, multi-core giant cell). Circulating monocytes have almost all the properties inherent to macrophages and are the main protagonists in the implementation of immune inflammation, which forms the basis of DTH. Thus, monocytosis in the presence of clinical signs of allergic disease indicates in favor of DTH.

CD4. This is mainly a helper subpopulation of lymphocytes. The increase in this fraction is observed in both ITH and DTH. In light of the presented data on the role of Tx2 and Tx1 in ITH and DTH, the determination of the dominance of Tx2 or Tx1 in the total CD4 cell subpopulation is of greatest diagnostic value. The determination of the secretory markers Tx1 (IL-2, IFgamma) and Tx2 (IL-4, IL-5) can be of great help in this regard. Thus, an increase in the level of IL-2 and Ifghamma combined with the definition of CD4 will be in favor of DTH; an increase in the level of IL-4 and IL-5 combined with CD4 will be in favor of ITH. Additional information may be provided by the definitions of IL-12, FNO-Alpha and FNO Beta, whose increased content induces CD4 differentiation towards Tx1 (DTH).

CD8. Initially, cells with these receptors were attributed to suppressors. At present, they are mainly cytotoxic (T-killers), but they also have a suppressor effect. In particular, these cells produce a factor with a molecular weight of 30000, which suppresses the production of IgE. Thus, the reduction of CD8 cells is a risk factor for ITH-related allergic diseases and, if clinically indicated, is in favor of ITH.

CD20. The cells identified by this marker are B-lymphocytes. If there are clinical signs of an allergy, CD20 increases indicate more in favor of ITH. However, the joint identification of CD20 and CD23 cells is of greatest value because CD23 cells produce factors with a molecular weight of 60,000 and 15,000 that enhance the production of IgE. However, the CD23 (soluble form), which is not fixed on the cell surface, interacts with the B-cell receptor complex, in particular with CD19, triggers a signal to amplify the proliferation of IgE+-B cells and their secretion of IgE. Thus, the detection of CD23 cells and especially of the soluble CD23 receptor form may play a significant role in the diagnosis of ITH, but at present these indicators cannot be used in broad clinical practice, as they have not yet been clinically tested in this aspect.

IgE. This immunoglobulin is known to be the main actor in ITH. The definition of IgE distinguishes between its general content and its specific IgE (for a specific antigen). In this section, we will talk about total IgE. An increase in IgE is evidence of a ITH, but it does not always indicate the presence of an allergic disease, since a ITH is a protective reaction, as mentioned earlier. In its handbook for practitioners

Л. Yeager (1990) provides diagnostic guidelines on the probability of allergic diseases depending on the level of IgE.

The definition of IgE in secrets can also be of great help.

IgA. This immunoglobulin as well as IgE is secreted mainly in the mucous membranes. Antagonistic relations of IgA and IgE are noted. Decrease of IgA level is accompanied by compensatory increase of IgE level.

Another mechanism of this antagonism is possible - IgA deficiency is the cause of increased permeability of the mucosa that promotes allergen penetration. Thus, a decrease in IgA is an indirect sign of an increase in IgE and the dominance of ITH in the presence of clinical signs of allergic disease. Reducing IgA in healthy individuals may serve as a criterion for placing them at risk for allergic diseases. Simultaneous determination of IgA and IgE values is desirable, since a combination of increased IgE and reduced IgA is much more reliable than each of these tests separately indicates in favor of ITH.

IgG. It has already been mentioned that the level of IgG, especially IgG4, competes with IgE in relation to the allergen (blocking antibodies) on which, in fact, specific immunotherapy (SIT) is based. On the one hand, this fact makes it possible to use IgG reduction to determine the role of ITH in the presence of clinical signs of allergic diseases and to attribute healthy persons with such changes to the risk group of allergic diseases in the combined reduction of IgA and IgG; on the other hand, the increase of IgG level in the process of SIT allows to predict its effectiveness.

We have presented the clinical characteristics of immunological tests, which are the most acceptable from our point of view for pathogenetic diagnostics of allergic diseases, but it should be emphasized that each of them has limited diagnostic value and therefore should be used in combination.

Simultaneous study of these parameters and identification of the shifts indicated in the table allows to determine reliably enough the priority of ITH or DTH in the pathogenesis of allergic disease and prescribe correct therapy.

In terms of identifying allergy risk groups and taking into account the laboriousness and availability of laboratory tests, we propose to determine the number of eosinophils, basophils, monocytes, IgA, IgG, IgE.

Biochemical pathogenetic diagnostics

It is primarily related to the determination of BAS levels and is mainly relevant for ITH diagnostics. Ideally, it is desirable to identify the main BAHs involved in the implementation of ITH (histamine, serotonin, bradykinin, slow reacting substance, etc.), but in real life it is quite time consuming and expensive research, currently used mainly for research purposes. Therefore, as before, the main place in pathochemical pathogenetic diagnostics belongs to histamine. Increased content of histamine in the blood can be a point of reference in diagnosis. However, the most justified from both diagnostic and economic points of view is to determine a number of phenomena associated with histamine.

In 1952, Parrot and Urquia discovered the ability of healthy people's blood serum to bind free histamine and called this property histaminopexy. They proposed a way to quantify this phenomenon, called the histaminopexy index (HPI), and found that a decrease in HPI below 30% indicates an allergic condition. Later their data were confirmed by numerous researchers and HPI became widely used in diagnostics of allergic diseases.

In 1961, Mikol, Renoux, Merklen discovered the antihistamine factor (AHF), which reflected another side of histamine serum binding, since the histaminopexy ability of the serum was lost when heated for two hours at 56 C; while the ability of the serum to agglutinate histamine-loaded latex particles underlying the determination of AHF was fully preserved. Titer of AHF below 1/160 was typical for allergic diseases.

At present, these two parameters of pathochemical pathogenetic diagnostics of HPI and AHF have been undeservedly forgotten, and we found it necessary to give a detailed description of the method of their determination.

Histaminopexy index (HPI).

Principle of the method: a known concentration of histamine is added to the dialyzed (to remove free histamine) blood serum. In the test tube histamine is added before the deposition of proteins with trichloroacetic acid (DPTA); in the control tube - after deposition. Extinction of experience and control on spectrophotometer is compared. The difference between extinctions, expressed in percentages, allows for the percentage of serum histamine binding.

Reagents: physiological solution, 5% DPTA, ether, 0.01% histamine solution, 5H sulfuric acid, 4% sodium nitrate solution, 25% Na2CO3 solution, 0.5H caustic soda solution, 10% sodium nitrate solution, sulfonylic acid solution (0.9 g). sulfonylic acid is dissolved in a mixture of 9.0 concentrated hydrochloric acid and 100.0 bidistilled water).

Dialysis: 0.5 ml. serum is placed in a cellophane bag, which is immersed in a 0.5 liter flask with physiological solution. Dialysis lasts 24 hours with three changes of physiological solution.

Reaction course: dialyzed and 20 times diluted serum is poured into 2.0 ml in 2 tubes (control and experience). In the first tube 0.25 ml 0.01% of histamine solution is added, kept at room temperature for 3 minutes, then in both tubes 2.25 ml 5% DPTA is added. After 30 minutes standing, both tubes are centrifuged for 20 minutes at 3000 rpm. After centrifugation the supernatant is gently transferred into clean dry tubes, 0.25 ml 0.01% histamine solution is added to the control tube and both samples are acidified with 0.15 ml 5H sulfuric acid, then ether is extracted (3 times 3.0 ml) in the dividing funnel. Transfer 2.0 ml of aqueous fraction to clean dry tubes (keeping sample numbering and control), add 1.0 ml of 4% sodium nitrate solution and place in a boiling water bath for 3 minutes, then cool 5 minutes on ice. By this time it is necessary to prepare a diazo reagent: to 1.25 ml of the solution of sodium nitrate cooled on ice 10% should be added 0.5 ml of sulfanilic acid and brought to 10.0 ml with bidistilled water. After cooling, 1.0 ml of diazo reagent and 1.75 ml of carbon dioxide solution are added to both samples; after 1 minute 0.3 ml of 0.5H solution of caustic soda is added. Extinction of the obtained solution of pink color is immediately measured spectrophotometrically at a wavelength of 484 millicrons. Experience and control extinctions are compared. The control extinction should be above experience. Identical values are observed at zero histominopexy. Calculated by formula: HPI = (K - O): K*100, where K - control extinction; O - experience extinction.

Antihistamine factor (AHF).

Principle of reaction: latex particles are loaded with histamine (an antigenic reagent), after addition of the antigenic reagent to the test serum the histaminopexy ability of the blood serum is inactivated by heating the sample for 2 hours at 56 C. After holding the sample for 24 hours at room temperature and centrifugation, the agglutination of latex particles is taken into account. The reaction is estimated by the largest serum dilution (titre) in which there is still agglutination.

Reagents: latex (can be replaced by dermatol), sodium chloride, boric acid, 0.1H sodium caustic solution, 2% histamine dichlorohydrate solution.

Preparation of sodium-borne buffer: 8.5 g of sodium chloride + 3.1 g of boric acid + 59.0 ml 0.1H solution of caustic soda per 1 liter of distilled water, pH buffer is precisely brought to 8.2 at pH.

Preparation of a latex suspension (dermatol): 250.0 ml of sodium-boronate buffer is added to 10.0 g of latex, the mixture is thoroughly shaken and left at room temperature for 1 hour. The supernatant is gently sucked into centrifuge tubes and centrifuged for 10 minutes at 3000 rpm. The sediment obtained after centrifugation is diluted in 10.0 ml of sodium-barrel buffer. The suspension is kept in a refrigerator for 2-3 months at +4оС.

Preparation of antigenic reagent: 1.0 ml of prepared latex suspension and 0.5 ml of 2% histamine solution are added to 5.0 ml of sodium-boronate buffer. The mixture is placed in the shaking device for 30 minutes and then kept at room temperature for 24 hours.

Reaction course: prepare a series of successive dilutions of the test serum (1:10; 1:20; 1:40; 1:80; 1:160; 1:320; 1:640). To 10 drops of each serum dilution 3 drops of antigenic reagent are added, shaken and placed in water bath at 56 C for 2 hours. Samples after heating are kept at room temperature for 20-24 hours, after which they are centrifuged at 2300 rpm for 3 minutes. The reaction is evaluated directly in tubes after preliminary shaking over the concave mirror. The criterion of positive reaction is the presence of distinct agglutinate flakes.

Possible sources of errors: inaccurate determination of the pH of the buffer solution, temperature fluctuations when kept in a water bath below 54o and above 58oC, not accurate preparation of antigenic reagent. At staging of each reaction the following controls are put: whole blood serum + latex suspension; serum in dilution 1:10 + latex; antigenic reagent + buffer solution; antigenic reagent + physiological solution; buffer solution + latex. All controls should be negative.

Etiological diagnostics

At the heart of the etiological diagnostics is an attempt to determine with the help of paraclinic tests a specific antigen causally significant for the development of this specific allergic disease. All paraclinic tests used for this purpose can be divided into two large groups:

• In vivo diagnostic tests;
• In vitro diagnostic tests.

We give preference to the latter. However, before giving a brief description of these tests, it should be emphasized that the cornerstones of etiological diagnosis are allergic anamnesis and clinical data. It is the carefully and qualitatively collected allergological anamnesis that makes it possible to choose from an extremely large number of allergens that should be used for paraclinic diagnostics. For example, the emergence of an exacerbation of allergic disease in the flowering season of plants requires the use of pollen allergens for paraclinic diagnosis, year-round exacerbations indicate in favor of allergens of house dust, connection with raw rooms - allergens of mold fungi; the connection of the disease with the emergence or exacerbation of infections indicates in favor of bacterial allergens; increased symptoms of allergic disease in the evening and night hours are more often associated with tick bedding allergens; connection of the disease with food consumption - food allergens, etc.

It should also be remembered that the results of paraclinical studies only then have diagnostic value, if they are confirmed by clinical data.

Diagnostic tests in vivo

These include skin tests and provocative tests, which are conducted directly in the patient.

Skin tests are subdivided into skin tests (application, compression, drip, etc.), scarifying tests, injected skin tests, modified prick test, Rebuc skin window, intradermal tests.

General conditions for all in vivo diagnostic tests - they must be carried out by professionals in specially equipped rooms to provide emergency care. Therefore, we will not dwell on the technique of conducting them, etc., as this work is designed for a general practitioner.

From the point of view of a general practitioner, it is necessary to know that skin tests are carried out only in remission of an allergic disease; they are contraindicated in the acute period of any other (non-allergic) disease, during pregnancy, lactation, in the first 2-3 days of the menstrual cycle; in the absence of a convincing anamnesis and preliminary examination, indicating the presence of allergic disease.

Application, compress and drip samples are more often used to detect sensitivity to chemical and medicinal antigens, especially in the case of allergic dermatitis. Their advantages include the minimum probability of complications; the disadvantages are low sensitivity. Therefore, whenever the doctor suggests a high degree of sensitization, etiological diagnosis should begin with skin (epicutaneous) samples.

Scarifying samples, injection test and prick test are more frequently used for a medium degree of sensitization. Currently, the prick-test is the most common among these samples. The difference from the usual prick test is that after the needle is injected at an oblique angle through a drop of an allergen into the surface layers of the skin, it rises with the sharp end of the needle. A variant of the prick test is to perform this test with lancets (phases) covered with the allergen. The skin window according to Rebuck is a modification of the scarifying sample with the only difference that the notches on the skin surface after allergen application are covered with a cover glass, which is removed after 24 hours to identify the cells that migrated to it. An indicator of an allergic reaction is eosinophilia exceeding 5%.

Intracutaneous samples are much more sensitive than previous ones, but they are much more often accompanied by complications associated with exacerbation of the underlying disease, up to the development of anaphylactic shock. Therefore, indications for intracutaneous samples are negative or questionable results of previous samples (epicutaneous, prick-test, scarifying, etc.). It is most expedient from the point of view of "no harm" at the beginning of prick-test setting and only in case of negative or doubtful results of intradermal tests, of course, provided that there is enough clinical data confirming the presence of allergic disease.

By the nature of skin reactions to the allergen, they may be immediate early (15-20 minutes); immediate late (8 hours after the disappearance of the early reaction); slow (12-48 hours after sample placement) and arthus-like (3-6 hours after sample placement). Immediate early reactions are characterized by hyperemia and swelling (blister). Immediate late and delayed reactions are characterized by hyperemia, infiltration and papula. Arthus-like reactions are characterized by hyperemia, infiltration and hemorrhages, often with vascular necrosis.

In terms of severity, immediate reactions are estimated as follows: negative reaction (-) - no difference from control; doubtful (+-) - erythema less than 10 mm, blister in the center less than 5 mm; slightly positive (+) - erythema more than 10 mm, blister in the center 5-9 mm; moderately positive (++) - erythema and blister in the center more than 10 mm; sharply positive (+++) - erythema and blister with pseudopodia 15-19 mm; very sharply positive (++++) - erythema and blister with pseudopodia more than 20 mm, lymphangitis, peripheral blisters, general reactions.

Immediate late and delayed reactions are evaluated by erythema and infiltrate (papule) diameter: doubtful - up to 7 mm; positive - 8-19 mm; moderately positive - 20-29 mm; sharply positive - at least 30 mm in diameter.

When prescribing skin samples, the doctor should remember that they can be false-negative and false-positive.

The following circumstances may lead to false-negative results:

• vascular disorders in cold seasons (it is necessary to warm up to normal temperature;
• daily biorhythms (it is optimal to conduct samples at 11 o'clock);
• age (in younger children, skin samples are less pronounced than in adults);
• medications: antihistamines should be cancelled 3-7 days before sampling. Euphylline and corticosteroids in dose < 30 mg converted to prednisolone do not affect sample results.
• Sample placement immediately after reactions caused by massive allergen doses;
• exceeding the shelf life of the allergen.

False positive reactions may be associated with:

1. a high concentration of an allergen;
2. the irritant effect of the allergen;
3. excessive traumatization of the skin during the sampling;
4. hypersensitivity of the skin.

Л. Yeager (1990) offers the following skin sample evaluation options in combination with clinical data:

• If the skin sample is positive and the allergen is known (from the allergological history), the fact of sensitization is not in doubt.
• If the skin sample is negative and no allergen is identified in the allergy history, the allergens used for the skin sample are unlikely to cause disease.
• If the skin sample is positive and there is no history of allergens that are positive in the skin sample, the results of the allergological history must be reviewed and the true cause of the positive sample must be verified.

Provocative specimens. These are used to confirm the causal significance of the allergen in cases of a discrepancy between the anamnesis and the skin sample.

It is categorically contraindicated to conduct provocative samples for non-specialists and in the absence of emergency medical care, especially in cases of inhalation provocation.

Most often the following versions of provocative samples are used: conjunctival, nasal, inhalation, oral. An indicator of a positive sample is an exacerbation of symptoms of the corresponding allergic disease.

The opposite of the provocative is the sample with the exception of the alleged allergen, established on the basis of allergic anamnesis. This test should be carried out by each doctor, because the reduction of clinical manifestations of the allergic disease with the exclusion of the alleged allergen not only confirms its etiological role in this disease, but also serves as a prediction of the effectiveness of treatment.

In vitro diagnostic tests

From our point of view, these are the most effective and safe etiological tests for allergic diseases, which in the future should replace the tests in vivo except for the sample with the exception of the alleged allergen.

The radio allergy adsorbent test (RAAT) is the most common of these tests. RAAT measures the level of antibodies specific to allergens. The essence of the method is that if there are allergen-specific IgE antibodies in the blood, they bind to the corresponding allergens fixed on the inert matrix. After the addition of radioactive anti-IgE antibodies, they bind to the resulting allergen-IgE allergen complexes and taking into account the radioactivity gives the level of IgE-antibodies specific to this allergen. RAAT allows for allergy diagnostics in the acute stage of the disease as well; the test results are affected by pharmaceuticals and other factors; there is a good correlation between the test and the disease severity. The main disadvantage of RAAT is its rather high cost. However, the appearance of various modifications of RAAT (enzymatic allergoadsorbent test, fluorescent allergoadsorbent test, combined allergoadsorbent test, immunoperoxidase system, etc.) allows us to hope to overcome this disadvantage.

The Shelley test or indirect test for degranulation of basophils has also become widespread. The reaction is based on the binding of animal Fc-fragments of IgE-antibodies by basophils when adding serum to these cells of patients with allergic diseases. After the addition of IgE allergens specific to these IgE antibodies, there is a degranulation of the allergens sensitized in this way basophils and release of BAS. An indicator of the reaction is the percentage of degranulated basophils.

In addition to these most common tests, the passive hemagglutination reaction (PHR), the precipitation reaction, the indirect test of human allergens degranulation, the immunoblotting method, the determination of serum allergen neutralizing activity, the reaction of granulocyte allergen specific damage, etc. are used.

Etiological diagnostics is of primary importance not for the diagnosis of allergic diseases, but for therapy, because only with adequate etiological diagnostics can effective specific immunotherapy (SIT), which allows you to count on long-term remission.

Treatment of allergic diseases

In fact, every doctor faces this problem, however, most of them leave a feeling of dissatisfaction with the results of allergic diseases treatment. We have analyzed enough literature on this problem and regret to note that the general trend of all the recommendations on treatment of allergic diseases fits into attempts to get the maximum result with minimum labor costs, against which in due time warned young doctors A.F. Bilibin. Most doctors after graduation are quite clear that when meeting with allergic diseases, it is necessary to use antihistamines or other BAS neutralizers, and this idea is usually consolidated for the rest of your life. Indeed, neutralization of BAS, which is the basis of the pathochemical stage of ITH, gives a rapid and vivid clinical effect, preventing pathophysiological disorders, which are the basis of clinical manifestations of most allergic diseases, but this is only part of the pathogenesis, a consequence, not the cause of allergic diseases and gives the patient only a break, not treatment. The lack of pathogenetic thinking when meeting with allergic diseases and the focus of treatment on the pathochemical stage, is probably one of the factors in the widespread allergic diseases currently observed. To a certain extent, this trend is supported by pharmaceutical companies, which are orienting their developments towards the creation of new generations of antihistamines or complex effects on BAS and advertising them intensively.

At the same time, the treatment of allergic diseases is a complex and time-consuming process that requires considerable effort and time from the attending physician and is based primarily on pathogenetic thinking. Only with this approach, we can count on real results in the treatment of allergic diseases.

On the other hand, allergic diseases based on ITH and DTH cannot be treated equally. These are different pathogenesis and therefore different therapeutic approaches.

It is from these positions - pathogenetic thinking, complexity and differentiated therapy of ITH and DTH that we want to present the main directions of treatment of allergic diseases.

General principles of treatment of allergic diseases (ITH and DTH)

Immunocorrection

First of all, it is necessary to clearly understand that allergic diseases never develop in a perfectly healthy person - it is necessary to have an initial immunocompromise, which may not occur clinically (immunodeficiency) or have clinical markers (immune failure). Both in the first and in the second case, immunocorrection is necessary, which may have an independent meaning in the treatment of this allergic disease. However, immunocorrection should not be understood only as the use of immunoactive drugs based on the definition of the immunogram. The fact is that in the vast majority of cases, immunodeficiencies and immune insufficiency are secondary and require clarification of the cause. It is the discovery of the cause of immunocompromination and the impact on it that is the main condition for effective immunocorrection. Our clinical experience allows us to identify the following main reasons underlying immunocompromination:

• Digestive disorders associated primarily with dysbacteriosis, enzyme and dyskinetic disorders;
• regulatory disorders associated with frequent stress or low tolerance for them, increased emotionality or lability of the nervous system, neurovascular disorders;
• metabolic disorders related to disorders of quantity and quality of nutrition (primarily protein nutrition), liver pathology, endocrine disorders.

Probably, there is no need to detail the means and methods aimed at eliminating these causes, as it is the individual creativity of each doctor, but there is an urgent need to emphasize that only this way can really help patients with allergic diseases. For example, in some patients with atopic dermatitis, correction of dysbacteriosis led to normalization of clinical data, persistent and prolonged remission. We observed patients with bronchial asthma, in whom the use of nootropics allowed to abandon inhalers and glucocorticosteroids. At the same time, it should be emphasized that finding out the causes of immunocompromination is a rather long and laborious process associated with examinations, consultations with specialists, careful collection of anamnesis, etc., but when the true cause is found, we can really count on effective help.

The impact on the cause can be combined with the use of immunotropic drugs based on and under control of changes in the immunogram, however, immunotropic drugs do not have an independent meaning in the correction of immunodeficiencies and immune insufficiency. Among immunotropic preparations in allergic diseases preference should be given to those acting on macrophagal phagocytic system (lycopid, sodium nucleinate, methyluracil, pentoxyl, etc.), because one of the main conditions for the quality of specific immune response is the quantity and quality of antigen-representative cells.

Effects on other causes and conditions that contribute to the formation of allergic diseases

Previously, it was noted that the condition of the skin and, especially, mucous membranes is of fundamental importance for the development of allergic diseases. In this regard, the diagnosis and treatment of pathological processes associated with them plays an essential role in the effective treatment of allergic diseases. This direction becomes especially important in food allergies, because sensitization may be associated not only with the quality of the allergen, but also with its excessive amount, which comes when the digestive limit of the gastrointestinal tract is exceeded due to pancreatitis, cholecystitis, gastritis, duodenitis, etc. Treatment of these nosologies is at the same time a pathogenetic treatment of allergic diseases. An important role in the treatment of allergic diseases is played by skin care and hygiene of the oral cavity and other mucous membranes (regularity of nutrition and physiology, fight against constipation, diarrhea, flatulence, etc.).

Orientation of the immune system to ITH or DTH, which is the basis of allergic diseases, is determined by the peculiarities of the antigen. Therefore, attempts to identify these antigens and, if available, sanitation from them should have a significant place in the allergy treatment program. In the case of ITH, these are primarily parasitic infestations (helminths, giardias, etc.), chlamydia, viral infection (respiratory syncytial virus, herpes viral infection, etc.).

In DTH - microorganisms that have lipid complexes (tuberculosis infection, mycoplasma infection, brucella, etc.).

Thorough elimination of parasitic, viral and other infectious diseases, and, if they are available, quality treatment, is a prerequisite for pathogenetic treatment of allergic diseases.

Exclusion of causal factorh

Along with the previous ones, it is one of the most effective areas of allergy treatment, however, it is also one of the most time consuming, because only the precise identification of the causal factor (allergen) and the presence of conditions to avoid contact with the patient can give clinical effect. Often, the elimination of the causal factor is possible in drug allergies; often this can be achieved in food allergies, but it is almost impossible to exclude contact with an allergen if the cause of the allergy is associated with air allergens in environmental ill health. At the same time, attempts by the attending physician to identify and eliminate the causal allergen must be persistent and systematic.

The basis for excluding a causal factor is an allergic anamnesis, confirmed by the etiological diagnosis in vitro or in vivo.

Ideally, however, it is not always possible to achieve this, so clinical experience allows a number of techniques or methods to limit contact with the most frequent and aggressive allergens and factors that provoke exacerbation of allergic diseases.

Most often they are associated with the patient's home, his diet and non-specific elimination of allergens from the body.

Home of a patient with allergic disease. The bedroom should not have upholstered furniture, rugs, heavy drapes - everything that can contribute to the accumulation of dust. Furniture and all other items in the room should be washable, pillows should be made of dacron or foam rubber, wet cleaning 1-2 times a week. During the cleaning and another 3-4 hours after it the patient should not be at home. It is not recommended to keep animals in the house, use sprays with a sharp smell. Do not make sudden changes in temperature in the room. The temperature should be constant and even no higher than 22oC, humidity no higher than 50%. It is desirable to have an air conditioner or any other room air cleaning device in the bedroom. It is strictly forbidden to smoke in the house. You should not ventilate the room during flowering of plants. It is desirable to have a cooker hood in the kitchen.

Nutrition for a patient with allergic disease. When identifying an allergen, it is excluded from the diet. Special diets for allergy to cow's milk, eggs, wheat, gluten, soybeans, corn, etc. are developed. In the implementation of these diets, it should be remembered that you should not eat not only the products in their natural form, but also their derivatives and impurities, which may be contained in completely different products by name, so it is necessary to carefully study the composition of food used in a patient with allergic disease, which is usually given on the package. However, more often than not, the exact identification is impossible and the so-called non-specific hypoallergenic diets are used. Here is one of them, which is recommended for patients with urticaria and swelling Quinque, but can also be used in any other allergic disease with an undetermined causal factor.

It is a hypoallergenic diet. It should be excluded from the diet:

• citrus (oranges, mandarins, lemons, grapefruits, etc.);
• nuts of all kinds;
• fish and fish products
• crabs, crayfish, shrimps and products containing them;
• bird (chicken, goose, duck, turkey, etc.);
• chocolate and chocolate products;
• coffee;
• smoked products;
• vinegar, mustard, mayonnaise and other spices;
• horseradish, radish, radish;
• tomatoes;
• mushrooms;
• eggs;
• fresh milk;
• strawberry, strawberry, melon, pineapple;
• butter dough;
• honey;
• all alcoholic drinks, including beer;
• non-alcoholic carbonated sweet drinks (pepsi cola, fanta, etc.).

You can eat:

• beef nonfat boiled;
• cereal or vegetable vegetable soups vegetarian or on the secondary beef broth;
• butter, olive, sunflower;
• boiled potatoes;
• buckwheat porridge, oatmeal, rice;
• lactic acid products (cottage cheese, buttermilk, yogurt);
• fresh cucumbers, parsley, dill;
• baked apples, watermelon;
• tea;
• sugar;
• compotes from apples, plums, currants, cherries, dried fruits;
• white unfruitful bread.

Nutritional value should be 2800 kcal. The food should include complete proteins (at least 160 g), carbohydrates (200 g), fats (140 g) and vitamins, trace elements and amino acids according to the daily needs specified in the treatment section of Lyell syndrome.

Nonspecific elimination of allergens. This treatment area has recently attracted increasing attention from clinicians, as it is one of the effective and efficient components of comprehensive allergy treatment, especially drug and food allergies.

Medicine began with efferent therapy (bleedings, leeches, diuretics, choleretic, laxatives, etc.), but the twentieth century has become the century of afferent medicine: every doctor and the patient himself tries to prescribe something or introduce any available ways and means. These constant attempts to introduce something into the body have reached a level rightly called medical intervention by a number of clinicians. However, it is well known that the elimination possibilities of the body are not infinite and they need to be periodically given a break. The need for such breaks has come to us from the depths of the ages in the form of periodic posts, which are present in all religions.

However, "medical posts" in the treatment of chronic diseases in doctors does not exist. It seems to us that a variant of "medical fasting" is a mandatory inclusion in the therapeutic arsenal of efferent methods of treatment aimed at removing various kinds of ballasts and slags from the body; and a rational combination of afferent and efferent methods of treatment should become a mandatory therapeutic basis of the twenty-first century.

This combination is of primary importance in the treatment of allergic diseases, since the removal of the causal factor (allergen) is the basis of treatment. In this regard, non-specific elimination of the allergen by means of efferent therapy is the most available for a wide range of clinical practices.

The nonspecific elimination of allergens is based on a combination of sorption methods and the activation of natural mechanisms of removal.

The essence of the method of such elimination is as follows: adsorbents are prescribed 2-3 times a day during two weeks; laxatives are used against them twice a week. If adsorbents provoke stool retention, laxatives should be used daily.

The most available adsorbents are Polisorb MP, Polyphepane and activated carbon. Polisorb MP - a single dose of 2-3 g is diluted in 100 ml of water (suspension) and taken orally 1 hour before a meal or medication.

POLIFEPAN - 1 tablespoon of polyfepan (for children under a year - a teaspoon) is diluted in 100 ml of water and taken 1 hour before a meal. ACTIVITED COAL (better than tablets of activated carbon, containing activated carbon, white clay and sodium salt of carboxymethylcellulose) 4-6 tablets of 0.5 g each. (single dose) inside half an hour before meals.

For laxatives preference should be given to MORSHAN SLABILITY SALT from the mineral water of the resort Morshan and Karlovarska SALT (natural or artificial). Both of these laxatives are taken before dinner 1 hour before the meal, 1 teaspoon diluted in half a glass of water.

It is also advisable to use choleretic, diuretic and expectorant allergic diseases. In his reference book M. D. Mashkovsky (1985) gives recommendations on veroshpiron use in infectious allergic bronchial asthma, especially in combination with right ventricular insufficiency. SPIRONOLACTON (veroshpiron, aldactone) is used 0.1-0.2 g (4-8 tablets) 2-4 times a day. From choleretic acid we prefer NICODIN (hydroxymethylnikotinamide) 0.5-1.0 g (1-2 tablets) 3 times a day half an hour before meals, drinking half a glass of water. In addition to choleretic nicodine has a pronounced anti-inflammatory effect and it has hepatoprotective properties. Among the expectorants we recommend CYNOPREET, which has expectorant, secretolytic, anti-inflammatory and antiviral effects. It is prescribed for 2 drages or 50 drops 3 times a day. Very good AMBROCSOL: reduces the viscosity of the secret, stimulates the motor activity of the eyelashes of the shimmering epithelium, improves mucociliary transport; administration is possible in the form of tablets, capsules, inhalations, injections. Prescribe 2-3 days, 1 tablet 3 times a day, then 0.5 tablets 3 times a day.

In case of severe allergic diseases, as well as in case of their refractory nature to therapy, we recommend the use of Hemosorption, Plasmapheresis, Lymphosorption. At the same time, we consider these methods not as therapeutic in themselves, but as methods that create optimal conditions for the subsequent comprehensive therapy of allergic diseases. Hemosorption is especially shown at initially high levels of immunoglobulins (IgA, IgE). We have established that the clinical effect of hemosorption in bronchial asthma is most pronounced with high numbers of these immunoglobulins and is accompanied by their normalization, but within a month after hemosorption the immunoglobulins return to their original values, so we do not recommend several consecutive hemosorption sessions, but we believe that the most justified is to use this time gained for the most active complex therapy.

Treatment of allergic disease based on ITH

The treatment base for this group of allergic diseases is the general principles just described. In addition, they include exposure to the immunological stage of ITH or anti-IgE therapy, exposure to the pathochemical stage and exposure to the pathophysiological stage of ITH. However, each treating physician must be absolutely clear that exposure to the immunological, pathochemical or pathophysiological stage alone does not have an independent therapeutic effect and that exposure should be used only in conjunction with the general allergy therapy principles described earlier. The independent effect at these stages plays a role only in case of necessity to relieve the acute phenomena and to facilitate the patient's condition during treatment.

Impact on the immunological stage of the ITH

The main efforts of the attending physician should be aimed at reducing IgE production and increasing the synthesis of IgG and IgA.

Suppression of IgE products.

Taking into account the previously described mechanisms of IgE hyperproduction in ITH, it would be optimal to have in your hands the so-called "point immunocorrection" preparations - that promote selective increase or decrease of the level of specific cytokines or immunocompetent cells and orientate the differentiation of naive helpers towards Tx1. For suppression of IgE products due to the prevalence of Tx1 it is necessary to increase the CD8 cell population, decrease CD23, increase the level of IL-2, IL-12, IF-gamma, FNO, GM-CSF; decrease the level of IL-3, IL-4, IL-5, IL-10.

At present, practical medicine does not have this arsenal, but there are a number of immunotropic drugs that capture cells and cytokines involved in hyperproduction of IgE and the orientation of differentiation of naive Helpers towards Tx1. These drugs can and should be used in the complex treatment of allergic diseases based on ITH, as they allow to influence the immunological stage of ITH and significantly reduce the likelihood of the development of subsequent stages.

The drugs that contribute to the suppression of IgE products by shifting the differentiation of naive helpers towards Tx1 include: lycopid, cycloferon, amixin, and Echinacea. In addition, depending on clinical data and the nature of immunogram changes, thymus, polyoxidonium and tonsilgon may be prescribed for this purpose.

Lycopid - activates macrophages monocytes, increases the synthesis of IL-1, FNO, gamma-interferon; used 1 mg (1 tablet) under the tongue 2 times a day, the course of treatment 10 days. Lycopid practically has no side effects.

CICLOPHERON - stimulates the production of alpha, beta and gamma-interferon; CD4 and CD8 cell growth, has anti-inflammatory and antiviral effects, has low toxicity, does not cumulate: 0.3-0.6 g (0.15 g in a tablet) is applied half an hour before meals once a day on the scheme (days) 1-2-4-6-8-11-14-17-20-23-26-29. The drug can also be injected intramuscularly and intravenously.

AMIKSIN (tiloron) - induces the formation of interferons, including gamma-interfron, increases the production of IgA, IgG, IgM; normalizes the ratio of suppressor and helper subpopulations of T-lymphocytes, has antiviral effect, increases the overall tone; 0.125-0.25 g is used.

Once a day (0.125 g in a tablet) for two consecutive days, and then 48 hours later another 1-4 weeks. The drug is not used before the age of 14 years.

Echinacea PREPARATS (Echinacea purpurea, pallida, angustifolia) - activate the macrophage link, enhances the secretion of IL-1, IL-6, FNO, interferons of alpha and gamma; have antiviral and antibacterial activity. The most accessible preparation is IMMUNAL (contains Echinacea purple juice) - it is used 20 drops 3 times a day, the duration of treatment is not less than 1 and not more than 8 weeks. Echinacea is contraindicated for tuberculosis, HIV infection, multiple sclerosis and autoimmune diseases.

POLYOXIDONES - may simultaneously affect the immunological and pathochemical stages of ITH. Impact on the immunological stage is associated with increased production of cytokines and antibodies; impact on the pathochemical stage is associated with increased resistance of cell membranes to cytotoxic effects. The preparation is used intramuscularly, intravenously and rectally 6 mg once a day for three consecutive days, then another 5-10 days after a day. Polyoxidonium also has a detoxifying effect.

Thyme's PREPARATES (tactivin, thymogen, etc.) in allergic diseases are prescribed with laboratory confirmed CD8 cell reduction. To get the maximum effect it is recommended 7-14 days before the use of thymus preparations to prescribe leukopoiesis stimulants (sodium nucleinate, methyluracil, etc.). Thymogen is prescribed intramuscularly for 100 mg 1 time per day for 3-10 days in the evening (17-19 hours).

TONZILGON - a complex preparation of medicinal plants and herbs, increases the phagocytic activity of macrophages, production of interferons, reduces capillary permeability, reduces mucous membrane edema. In fact, tonsilgon affects the immunological (production of interferons) and pathophysiological (reduction of edema) stages of ITH. In addition, tonsilgone has anti-inflammatory, antiviral and immunomodulatory effects. It is used 25 drops or 2 drages 5-6 times a day in the acute stage of the disease and 3 times a day to stabilize the effect for another 2-3 weeks.

Increase in IgG and IgA products.

Earlier it was noted that IgE and IgG are equally specific to the antigen (allergen) that caused their products. Therefore, the excess of IgE and their preferred bond to the antigen will orient the immune response towards the ITH; with the dominance of IgG and the preferred bond of the antigen to them, a typical humoral immune response will occur. For these reasons, along with attempts to inhibit the synthesis of IgE, one of the directions in pathogenetic allergy therapy is to increase the production of IgG specific allergens, which, by competing with IgE for the allergen and predominantly binding it (blocking antibodies), will reduce or even eliminate the clinical manifestations of GHG-based allergic diseases. With respect to IgA, their antagonistic relationship to IgE has previously been noted.

This variant of pathogenetic therapy for allergic diseases exists and is called specific immunotherapy (SIT) or desensitization. At the same time, the mechanisms of therapeutic action of SIT have not been fully studied, because along with IgG blockade it is possible to develop immunological tolerance, increase IgA synthesis, decrease the degranulation ability of basophils and fat cells, decrease the proliferative and secretory activity of T-lymphocytes, etc.

We consider it possible not to give a detailed description of the method of SIT, because it should be implemented only by a specialist (allergic immunologist) in the presence of appropriate conditions described in the section of etiological diagnosis of allergic diseases, but attention should be paid to a number of provisions and conditions that a general practitioner should know.

The main indications for SIT are: pollinosis, allergic rhinitis, allergic conjunctivitis, atopic bronchial asthma, insecticide allergy. Carrying out SIT is possible only if the clearly proven causal value of specific allergens and the inability to eliminate them from the patient's environment, as well as in cases of ineffective drug treatment. SIT is carried out only in remission.

Contraindications for the SIT are: collagenosis, tuberculosis in the active stage, renal, liver and heart failure, gastric and duodenal ulcer, hemorrhagic vasculitis, mental illness, joining an allergic disease of the infectious process.

SIT is a long-term treatment and the clinical effect begins to show only 3-6 months from the beginning of treatment. There are pre-season and year-round versions of SIT. Preseason variant is realized in patients with pollinosis and begins no later than 3 months before the beginning of flowering plants. In the flowering season, the SIT stops due to the risk of systemic allergic reactions and resumes for the next year. Year-round SIT is used in allergic diseases unrelated to flowering plants, is carried out until the maximum tolerated dose of the allergen with subsequent constant administration of a maintenance dose at least once a month.

When prescribing the SIT should take into account the fact that often after a good clinical effect may be a sharp deterioration due to the expansion of the spectrum of sensitization, so the SIT in no way should not be considered as an independent method of treatment of allergic diseases, but only as one of the components of complex therapy. We believe that the indications for SIT, which is laborious and burdensome for the patient method, will narrow as knowledge of the pathogenesis of allergic diseases increases and as the spectrum of drugs for pathogenetic pharmacotherapy expands.

It is also necessary to remember that since the SIT involves a targeted increase in the synthesis of immunoglobulins, in order to obtain the maximum effect of the SIT it is necessary to create a number of conditions ensuring the optimal implementation of this task. These are: complete protein nutrition, activation of metabolism and stimulation of B-cellular link of the immune system.

At least two weeks before the SIT, the patient needs to provide enhanced and complete protein nutrition in combination with moderate anabolics, such as potassium orotate. Simultaneously with the beginning of the SIT it is recommended to use myelopid (the old name B-activin).

Potassium orotate (orotic acid) - has an anabolic and regenerating effect, providing the synthesis of pyrimidine nucleotides of the nucleic acids involved in the formation of protein molecules. Potassium orotate is administered to adults 0.5-1.0 g (children 0.25 - 0.3 g) 2-3 times a day 1 hour before meals. From the side effects of dyspeptic disorders and allergic reactions are possible.

MIELOPID - stimulates antibody formation; has neurotropical activity (in particular, analgesic effect), immunocorrective and antitumoral effect, stimulates functional activity of macrophages and cell differentiation. Myelopid is prescribed 3-6 mg once a day subcutaneously, 5 injections daily or every day.

Effects on biological Akims

Once again, it should be stressed that the impact on the pathochemical stage, based on which the neutralization of the effects of BAS, is not independent in the treatment of allergic diseases and should be used only for the management of acute allergic diseases in order to buy time and create conditions for comprehensive treatment. The next condition is that exposure to the pathochemical stage should be applied only in case of the dominance of ITH in the pathogenesis of this allergic disease.

Among drugs affecting the pathochemical stage, antihistamines are the most common. Theoretically, there are the following ways to block the effects of histamine: 1) inhibit histamine biosynthesis through suppression of histidine carboxylase enzyme, 2) stimulate its degradation through activation of histaminase, methyltransferase and monoaminoxidase enzymes, 3) inhibit its release, 4) block histamine access to its receptors (I. V. Sergeev, N. L. Shimanovsky, 1982). However, at present, clinical practice mainly uses drugs that block histamine receptors and access to them, therefore, histamine. There are blockers of H1- and H2-histamine receptors. H1-histamine receptor blockers are better known in practice as antihistamines; H2-histamine receptor blockers are known as antipeptic drugs because they are very active in the secretion of hydrochloric acid by the stomach. However, this approach is not quite correct, because through H2-histamine receptors the mechanisms of immunoregulation and, above all, the activation of suppressor activity of T-lymphocytes. In addition, the effect on H2-receptors inhibits the cytotoxic and helper activity of T-lymphocytes, inhibits the release of BAB from mast cells and basophils, lysosomal enzymes of neutrophils, etc. Previously, the increased permeability of capillaries was associated with the activation of H1-histmin receptors, but later it was found that the effect of increased capillary permeability can be eliminated only with the help of H1- and H2-histmin receptor blockers.

Thus, the most justified is the combined use of H1- and H2-histamine receptor blockers.

Blockers of H1-histamine receptors. They are divided into first generation and second generation blockers. The main difference between them is that first-generation blockers have sleeping pills and M-cholin-blocking effects (increased intraocular pressure, pupil dilation, reduced secretion of glands, tachycardia, hypertensive effect, lower intestinal tone and peristalsis, relaxation of the bladder, etc.). In addition to the described, there may be a number of side effects of the first generation blockers: epileptic seizures, especially in patients with focal brain lesions; nausea, vomiting, allergic reactions, weakness, decreased attention, disturbance of coordination, dizziness, headache, etc.). The most common of the first generation of H1-histamine receptor blockers are used: Dimedrol (diphenhydramine), Pipolphin (prometazine), SUPASTIN (chloropyramine), TAVEGIL (clamastin, rivtagil), PERITOL (ciproheptadine), DIMEBON, DIMETINDEN, ACRIVASTIN, TRANILAST, FENSPIRID (erespal), DIAZOLIN (mebhydrolin).

In contrast to the first generation of blockers, H1-histamine receptor blockers of the second generation do not cause sleepiness and do not have M-cholin-blocking effect. However, this does not mean that they do not have side effects. It is enough to enumerate the side effects of loratadine (claritin, clarotadine), a significant part of which is more or less inherent to other second-generation blockers as well, to the extent that the desire to prescribe them everywhere has clearly decreased: angioedema, back pain, asthenia, vision disorders, chest, eyes and ears pain; fever, calf muscle cramps, chills, upper respiratory tract infections, weight gain, tear separation and salivation disorders, sweating, thirst, hypertension-hypotension, palpitations, headache, fatigue, excitability, hyperkinesia, parasthesia, tremor, dizziness, nausea, vomiting, dry mouth, change in taste, anorexia, constipation diarrhea, dyspepsia, gastritis, flatulence, toothache, amnesia, anxiety, depression, insomnia, decreased libido, bronchospasm, discoloration, dysmenorrhea, menorrhea, vaginitis, breast pain, arthralgia, myalgia, dermatitis, photosensitization, itching, hives, etc. Of the second generation blockers, the following are used more often: LORATADIN (claritin, clarotadine), CETRISIN (cetrine), TERFANADIN, FEXSOFANADIN, ASTEMIZOL (histalong, stemis), AZELASTIN (allergodil).

Once again, it is necessary to emphasize the need to use H1-histamine receptor blockers only to relieve acute allergic diseases, short courses (no more than 7 days) and only when the ITH is dominant in the pathogenesis of this allergic disease.

With regard to the need for short courses, we are aware of the experimental data that have established the presence of hemorrhages and atelectases in the lungs, hemorrhages in the parenchyma of the liver when administering histamine receptor blockers to rats over 7 days. It is possible that under conditions of blockade of histamine-sensitive receptors and absence of influence on formation (histidine decarboxylase) and degradation (histamine) of histamine, the accumulation of histamine under these conditions may cause an independent damaging effect in humans, similar to that obtained in the experiment. Therefore, we insist on the short-term use of histamine receptor blockers, only for the treatment of acute manifestations and in no way use them for basic treatment. Antihistamines are only an episode in treatment, not a treatment.

If it is necessary to prescribe H1-histamine receptor blockers, it is better to use those that simultaneously block the receptors to other BAS. Very interesting in this respect is the drug phenspyride (erespal), which along with antihistamine activity blocks antiserotonin and antibradikinin receptors, reduces the production of pro-inflammatory cytokines and derivatives of arachidonic acid. Ciproheptadine has antiserotonin and antibradykinin activity. Dimebon and dimethyndene have antiserotonin and antibradykinin activity respectively.

Blockers of H2-histamine receptors. The rationale for the use of these drugs to affect the pathochemical stage of ITH-mediated allergic diseases has been previously given. However, in the literature available to us among the drugs of this group we have not found indications for their use in allergic diseases. With a certain "stretch", only "Ranitidine Sedico" can be recommended, as its mechanism of action points to antipeptic and antihistamine effects. In all other drugs, attention is fixed only on the antipeptic effect. This allows us to believe that at present we do not have H2-histamine receptor blockers designed to affect the pathochemical stage of allergic diseases.

More physiological than the blockers of H2-histamine receptors to BAS are drugs whose mechanism of action is connected with the counteraction of free histamine and other BAS from cells where they are mainly deposited (fat cells, basophils, platelets, etc.). The mechanism of action of these drugs can be divided into two groups: 1) preparations stimulating the formation of cAMF, inhibiting phosphodiesterase and reducing the transport of calcium through the membrane (cAMF-active) and 2) preparations normalizing free radical processes by restoring free radicals into a stable molecular form (antioxidants).

cAMF-active drugs. These drugs prevent the degranulation of mast cells and IgE-mediated release of BAS. Preparations of this group include: cromoglycic acid, necromil, ketotyfen, glucocorticoids, theophylline, etc.

It is hardly necessary to dwell in detail on the use of theophylline and glucocorticoids in the treatment of allergic diseases, as these drugs are well known and widely used. It is only necessary to warn against such a wide and often unreasonable use of glucocorticoids, as they should be used only for life reasons (emergency conditions) and in isolated cases in the absence of the effect of persistent and correct complex therapy. It should be emphasized once again that in the vast majority of cases, reasonable and correct comprehensive therapy solves all issues related to the treatment of allergic diseases and the need for glucocorticoids are really exhibitive cases, especially in no case should we start treatment of allergic diseases with glucocorticoids. As for theophylline and other drugs from the group of methylxanthins, the main scope of their use in allergic diseases - bronchial asthma.

CROMOGLICAL KISLOT (intaglio, kromheksan, kromogelsal combi, kromogen, kromoglin, kromosol, lecrolin, hi-crom). Preparations of cromoglycic acid are more often used in bronchial asthma in the form of aerosols, require systematic and prolonged use, as they prevent clinical manifestations of allergic diseases, but do not eliminate existing symptoms. Of all the medicinal forms of cromoglycic acid, only it is produced in capsules for oral use, the rest in the form of sprays and drops. Cromoglycyic acid is used orally at the age of over 13 years of 200 mg (2 capsules) 4 times a day half an hour before eating or sleeping, children from 2 to 12 years of age 1 capsule (100 mg). The side effects of oral administration include joint pain, a feeling of abdominal discomfort, nausea, vomiting, diarrhea, skin rash. The clinical effect develops in 2-6 weeks from the beginning of intake.

KETOTIFEN (nausea, zetyphene, ketaf). The drug is administered orally 2 times a day before meals for 1 mg (1 tablet); children ? - 1/3 tablet with gradual reduction after a persistent clinical effect for 2-4 weeks. Side effects: dry mouth, dizziness, drowsiness, thrombocytopenia, weight gain, skin allergies.

NEDOCROMIL (sodium necromil, tylede, tylede mint, tylarin) is used for bronchial asthma, inhaled 4-6 times a day, therapeutic effect at the end of the first week, then a maintenance dose of 2 inhalation 2 times a day. Side effects: headache, cough, bronchospasm, nausea, vomiting, abdominal pain.

Antioxidants. These drugs either directly bind free radicals (direct antioxidants), or stimulate the antioxidant system (indirect antioxidants). They include preparations based on vitamin E, beta-carotene, dimephosphone, cytochrome C, antitoxinate, hypoxene, oxyx, pumpkin, etc. These antioxidants are also known as antioxidants. Antioxidants due to the absence of a pronounced side effect and good clinical effect due to the membrane stabilizing effect should be more widely used in the treatment of allergic diseases.

However, the problem of creating antihistamine drugs affecting histamine metabolism remains acute.

One of the mechanisms to neutralize free histamine is its binding to plasma proteins. This phenomenon is first described by Parrot and Urquia and is called histaminopexy. The histaminopexy of calcium and histaglobulin increase their ability. It is these drugs, as have passed the test of time and proved themselves well, we primarily recommend for exposure to the pathochemical stage of allergic diseases as therapeutic, and are very cautious about the previously listed blockers of antihistamine receptors. When prescribing calcium and histaglobulin drugs, you should not use potassium preparations, which depress histaminopexy.

We consider it appropriate to bring a simple and effective treatment scheme with calcium and histoglobulin. Glycerophosphate, calcium gluconate and calcium chloride, especially the latter, are the most suitable allergic diseases for treatment. The general contraindication for the prescription of calcium medicines is hypercalcemia, atherosclerosis, propensity to thrombosis. Calcium Chloride is prescribed to adults 10-15 ml (1 tablespoon) to children 5-10 ml (1 teaspoon) 5-10% of the solution, 3 times a day after meals for a month. Simultaneously with calcium preparations, GISTAGLOBULIN is administered according to the following scheme: 0.1 - 0.2 - 0.3 - 0.5 - 1.0 - 2.0 - 2.0 - 2.0 - 2.0 - 2.0. Only 10 injections, children under 12 years old maximum dose of 1.0 ml. Each injection is strictly subcutaneously made after 2 days on the 3rd one. If there is a reaction to the injection of initial doses in the form of a moderate exacerbation of allergic disease, then this dose is prolonged until the reaction disappears. For example: 0.1 - 0.1 - 0.2 - 0.3.........; or 0.1 - 0.2 - 0.2 - 0.3 - 0.3 - 0.3 - 0.5........, however, the total course should not exceed 10 injections. Doctor should remember that the effect can occur after the first course of treatment, but the maximum and persistent effect is usually shown after the third course. The breaks between courses should be monthly, and since each course of treatment also lasts a month, the total duration of treatment is 5-6 months. Once again, it should be emphasized that this treatment scheme is the most harmless and effective, but only with sufficient duration, so regardless of the good clinical effect after the first course, the doctor should insist on two more cycles.

Effects on pathophysiological manifestations

This stage of pathogenesis is based on an attempt to eliminate the effects of BAS associated with spasm of smooth muscle muscles (primarily bronchoconstriction) and swelling. For this purpose, alpha-adrenomimetics (adrenaline, noradrenaline, naphthysene, sanorin, nazivine, tetrisoline, phenylephrine, etc.) are used more often. ), beta-2-adrenomimetics (salbutamol, terbutaline, M-cholinolytics (atropine, platyphylline, baralgin, etc.), as well as myotropic spasmolytics (no-Spa, spasmol, papaverine, etc.). This direction of therapy should be considered only as symptomatic, although it is regrettable to note that often all treatment of bronchial asthma or vasomotor rhinitis is reduced to finding effective bronchodilators or vasoconstrictor drugs. This is unacceptable and harmful. Treatment of any allergic disease should be only complex.

Treatment of allergic diseases based on DTH

This is one of the most complex and undeveloped issues, as the basic literature on allergic disease treatment orients the attending physician to the absence of differences in treatment of ITH and DTH, and we have not found significant differences in the literature in treatment of these two fundamentally different pathological processes. At the same time, we strongly believe that only a differentiated therapy based on the specifics of the pathological process will make it possible to actually treat allergic diseases.

Previously, it has been noted that DTH, in contrast to ITH, does not have pathochemical and pathophysiological stages, because DTH is based on immune inflammation. Therefore, antihistamines and other ITH pharmacotherapy options will not be of significant importance in the treatment of DTH-mediated allergic diseases.

In principle, influences on the immunological stage, anti-inflammatory therapy and on the causative agent are the most important in DTH therapy. The treatment options described in ITH are only needed if DTH and ITH are present in the genesis of the allergy.

However, allergy treatment based on DTH should be started from the general principles described at the beginning of the section "Treatment of allergy diseases", as they also usually occur against the background of existing immune deficiency; chronic inflammatory pathology, including gastrointestinal tract, is also a risk factor and provokes the development of DTH-mediated allergic diseases; and options for nonspecific elimination and hypoallergenic diet should also be present in the complex treatment of DTH-mediated allergic diseases.

Etiological treatment has a special place in the treatment of this group of allergic diseases, because it is the specifics of the antigen, in particular the presence of lipid complex, which plays a crucial role in the development of DTH. From this point of view, differentiation of DTH into contact, tuberculin and granulomatous DTH suggested by R. Bernetson, W. Britton and D. Gawkrodger (2000).

Contact DTH manifests itself as an eczematous reaction at the site of antigen exposure and more often occurs in contact with chemicals (nickel, mercury bihloride, Peruvian balm, Catalysts used in the rubber industry, potassium dichromate, cobalt, wood resins, dinitrochlorobenzene), medicines (benzocaine, neomycin), poisonous plants (bag rooting, ivy poisonous, oak poisonous), etc.

Along with the general principles described above, the treatment of contact DTH is based on stopping contact with causal factors, local and general anti-inflammatory therapy; UV irradiation, inactivating Langerhans cells, which play a key role in the launch of contact DTH. Of the local anti-inflammatory drugs shown are compresses with chilled solution of Brown Liquid in dilution 1:20 for 25 minutes 3 times a day; TYKVEOL - lubricate the affected areas 2-3 times a day; Phytostimulin - gauze bandages or cream 2-3 times a day; in the absence of the effect can be used local glucocorticosteroids. Of the total anti-inflammatory action is shown the use of sodium Thiosulphate intravenously (30% solution 10-50 ml, per course of 10 injections) or per os 0.5 -1.0 g 2 times a day after meals; POLYOXIDONE, TONZILGON, glucocorticosteroids at the prevalence of the process and resistance to therapy.

Tuberculin variant of DTH appears on injection of tuberculin and other similar antigens (M. Leprae, Leishmania tropica, etc.). It is mainly a diagnostic version of DTH and is not essential in treatment practice.

The DTH granulomatosis variant is the most important one for clinicians because it is the main DTH-mediated allergic diseases: leprosy, tuberculosis, brucellosis, tularaemia, yersiniosis, pseudotuberculosis, sarcoidosis, Crohn's disease, leishmaniasis. It should be emphasized that this list, which will be expanded in due course, should be considered as DTH-mediated allergic diseases and the impact on DTH in them should be considered as one of the priority areas of pathogenetic therapy.

At the same time, the known difficulties in treatment of this group of diseases, in particular tuberculosis, and the lack of information on etiology in some nosologies (sarcoidosis, Crohn's disease) suggest that exposure to the immunological phase of DTH should also be a priority in the comprehensive treatment of DTH-mediated allergic diseases.

From the pathogenesis point of view, the main actors of DTH are T cells and macrophages monocytes, and activation of Tx1 and macrophages is one of the key components of DTH launch. Therefore, inhibition of cytokines contributing to this process, as in the case of ITH, is hardly feasible. Additional activation of macrophages is also unlikely to be necessary, as hyperactivated macrophages excessively producing pro-inflammatory cytokines may worsen the course of allergic disease and increase the severity of intoxication. From this point of view, the most acceptable impact on the immunological phase of DTH is such an impact, which along with neutralization of hyperactivation of macrophages would contribute to the increase of their lytic potential in relation to the antigen. It is also expedient to use preparations increasing the population of the main DTH cellular components (T-cells, macrophages-monocytes) when their reduction is documented on the basis of immunogram.

The following preparations deserve the greatest attention in this respect.

HALAVIT - has anti-inflammatory and immunocorrective effects, inhibits excess production of hyperactivated macrophages of pro-inflammatory cytokines, which contributes to the normalization of their functions, the restoration of antigen and regulating functions of macrophages; restoration of functions of T-lymphocytes. At the same time, halavit promotes physiological dilatation of blood vessels, prevents thrombosis and stimulates the microbocidal system of neutrophil granulocytes. It is used in the acute period 200 mg, then 100 mg 2-3 times a day intramuscularly until the signs of inflammation disappear.

GLUTOCSIM - stimulates the endogenous production of cytokines (IL-1; IL-4; IL-6; IL-8; IL-10; FNO; IF; erythropoietin, etc.). ), reproduces the effects of IL-2 through the expression of its receptors, has a differential effect on normal (stimulates proliferation and differentiation) and transformed (induces apoptosis) cells, stimulates cerebrospinal hemorrhage, restores the level of neutrophils, monocytes and lymphocytes in peripheral blood, the functional ability of tissue macrophages, has a systemic cytoprotective effect. It is used intravenously, intramuscularly, subcutaneously once a day for 5-40 mg depending on the nature of the disease; for a course of 50-300 mg; repeated course after 1-6 months.

These two drugs, especially glutoxime, are most suitable for the immunological stage of DTH-mediated allergic diseases and, along with exposure to the causative agent, should be part of their etiopathogenetic treatment complex.

In addition (independently or together with them) under the control of the immunogram can be used: POLYOXIDONE, LICOPID, TIMUS PREPARATES, SODIUM NUCLEINATE, METHILURATION, TONZILGON, NEOVIR (reduces FNO production, normalizes the CD4/CD8 cell balance; applied 250 mg in 48 hours, 5-7 injections per treatment),

LEIKINFERON (pharmaceutical form of cytokine complex, provides activation of immune response effects; helps to normalize the induced production of cytokines; normalizes the number of red blood cells, neutrophils, lymphocytes, platelets; has an anti-inflammatory effect; used 1-3 million IU intramuscularly 2 times a week until a stable clinical effect).

VOBENZIM, a balanced complex of enzymes with immunomodulatory, anti-inflammatory, anti-edematous, fibrinolytic and antiaggregating effects, can significantly enhance the effect of immunocorrection of DTH-mediated allergic diseases. It is used orally half an hour before meals, without biting the tablets with a glass of water, 3-10 tablets 3 times a day for 2-3 weeks; then reducing the dose (3-5 tablets) for another 2-3 months.

It is also shown in the complex treatment of DTH-mediated allergic diseases the use of antioxidants, primarily for the membrane stabilizing effect.

DIMEFOSPHON - membrane stabilizing, anti-inflammatory, immunomodulatory, antihypoxic and radioprotective effect. It is used orally at the rate of 1 ml 15% solution for 5 kg of body weight 1-4 times a day, with water, 7-10 days; intravenously - the contents of 1-2 ampoules should be dissolved in 200 ml 5% glucose or saline solution, drops (40-60 drops per minute), 1-4 times a day, 7-10 days. Cytochrome C - antihypoxic, cytoprotective action, activation of cellular metabolism. It is used intravenously, 10-100 mg is diluted in 200 ml 5% glucose or saline, slowly (30-40 drops per minute) 1-2 times a day for 10-14 days; intramuscularly 5-20 mg, 1-2 times a day, 10-14 days; inside 20 mg 4 times a day, 5-10 days. ANTOXINAT - tablets contain beta-carotene, vitamin C, vitamin E, zinc, copper, manganese, selenium. Use 1 tablet 2 times a day. HYPOXEN - antioxidant, antihypoxant. Apply inside 0.5-1.0 g 3 times a day for 3-14 days; intravenously 7% solution 2.0 ml dissolve in 200 ml 5% glucose or saline, inject drops (40-60 drops per minute), 1-3 times a day, 3-5 days.

Treatment of anaphylactic shock

As already mentioned, the basis of any shock is a sharp decrease in the volume of circulating blood, either through its loss or through depositing (sequestration). It is these two mechanisms that determine the treatment of different types of shock. Anaphylactic shock is a typical representative of the second mechanism (depositing), which is associated with the action of BAS on the microcirculatory channel (peripheral vasoconstriction - vasodilation).

In this regard, emergency aid in case of anaphylactic shock should be implemented in several directions:

1. Restriction of contact with the allergen;
2. Antihypoxic protection of the CNS;
3. Restoration of hemodynamics;
4. Immune response suppression;
5. Neutralization of BAS;
6. Correction of metabolic acidosis;
7. Correction of oedema and spastic syndromes, if necessary;
8. Reanimation measures.

First, it seems reasonable to characterize the actions and drugs in accordance with these directions, and then their implementation depending on the phase and stage of shock.

1) Restriction of contact with allergen: stopping the drug or removing it from the surface of the skin, applying a tourniquet above the place of drug injection (the tourniquet is applied for not more than 25 minutes), tingling the injection site with 0.1% hydrochloride adrenaline solution or 0.18% hydrotartarate adrenaline solution (0.5 ml in 4.5 ml of physiological solution), cold at the injection site. All these measures provide restriction of resorption at the place of injection of the causal factor. If anaphylactic shock is caused by penicillin, intramuscular administration of penicillinase in the dose of 1000000 IU is shown.

2) Antihypoxic protection of the CNS: position of Trendelenburg with the head end lowered (in case of consciousness impairment, turn the head to the side and extend the lower jaw to prevent tongue flap and aspiration of vomiting masses), adequate oxygen therapy - constant supply of moistened (Beaver's apparatus) oxygen through the nasal catheters, introduced to a depth equal to the distance between the ear and the tip of the nose (oxygen pillows are ineffective and serve as a source of oxygenation of the room where the patient is); use of antihypoxants from the group of tranquilizers (sibazone) and GABAergic (sodium oxybutyrate). Sybazone (diazepam, seduxenes, relaxium) has anticonvulsant and moderate sedative effects, promotes stabilization of hemodynamics, has a pronounced antihypoxic effect (decrease in oxygen demand from 7 to 38%); it is administered intravenously or intramuscularly in a dose of 0.3 mg/kg of body weight. It is available in 2.0 ml ampoules. 0.5% solution - in 2.0 ml. solution contains 10 mg. of sibazone. At intravenous injection a single dose should be diluted in 20.0 ml. 5-10% glucose, inject slowly (1-2 ml. per minute). Sodium oxybutyrate (SO) has sedative and anticonvulsant effects, in large doses it causes sleep and anesthesia; expressed antihypoxant, promotes normalization and increase of A.D., central venous pressure, increase in the volume of circulating blood. In shock, sodium oxybutyrate improves hemodynamics for 40-60 minutes even in the absence of correction of hypovolemia, which is indispensable in the transportation of the patient; has a positive effect on the acid-base balance (acidosis correction). Sodium oxybutyrate is administered intravenously 50-100 mg. per kg. body weight. It is produced in ampoules of 10.0 ml 20% solution (the ampoule contains 2 g of sodium oxybutyrate). The content of the ampoule is introduced slowly (1-2 ml/min) or diluted in 500.0 ml. 5% glucose and injected drip. It should be remembered that if administered quickly, all drugs of these groups may cause respiratory failure.

3) Hemodynamic recovery: warming the patient (warm blanket, warm to the feet, hot tea), Reopolyglyukin 400.0 ml. intravenously, 5% glucose 500.0 ml. intravenously, Ringer's solution or trisol 500.0 ml. trisol. intravenously. Begin infusions with 5% glucose jet under the control of A.D. If under the influence of 5% glucose systolic pressure increased to 80-90 mm. mercury column, switch to drip injection. Infusions stop when systolic pressure rises up to 110 mm. of mercury column. In the absence of the effect they switch to jet infusions of rheopoliglyukin with the subsequent transition to crystalloid solutions in accordance with the described control conditions.

Most of the recommendations for treatment of anaphylactic shock contain indications of the necessity to use adrenaline, however, its use should be strictly regulated by the stage of shock, because in the early stages of shock vasoconstriction dominates and the use of adrenaline or noradrenaline may worsen the patient's condition. For emergency orientation, the following clinical signs should be considered in the dynamics of shock:

• Prodromal period - hyperemia of the skin (action of BAS) - adrenaline is not shown.
• Erectile phase - pallor, sometimes hyperemia of the skin (beginning of vasoconstriction) - adrenaline is contraindicated.
• Shock I degree - pale skin, cyanosis of the lips and nail phalanges (pronounced vasoconstriction) - adrenaline is not shown.
• Shock II degree - spilled cyanosis (vasodilation dominates) - adrenaline is shown.
• Shock III degree - total cyanosis (dominated by vasoatonia) - the effect of adrenaline is questionable.

Thus, when cyanosis appears in 5% solution of glucose for infusions, 1,0 0,1% solution of adrenalin hydrochloride should be added and infusion should be performed as described above.

Infusion therapy should be persistent but correct: control of A.D., central venous pressure (CVP), diuresis. If the volume of infusion necessary for normalization of hemodynamics exceeds 1.5 liters, it is necessary to connect saluretics (lasix), or osmotics (mannitol), or their combinations. This variant of infusion therapy, which is called forced diuresis, should be carried out only by specialists in the intensive care unit and must necessarily be provided with very strict control over the diuresis, acid-base balance (ABB), electrolytes, blood clotting system.

An effective means of normalizing hemodynamics, especially microcirculation, is heparin. The preparation is injected intravenously 5-10 thousand units. An additional argument in favor of the mandatory use of heparin in anaphylactic shock is the presence of heparin immunosuppressive and antihistamine effects. The heparin is injected again after 4-5 hours under the control of the blood coagulation system.

The introduction of cardiac glycosides is also shown. Preference should be given to corglikon. It is injected into the vein 0.2-0.5 ml. 0.06% solution of preliminary diluted in 20.0 ml. 20% glucose or this corglycone dose is added to an IV with 5% glucose used for infusion therapy.

Ascorbic acid is shown to reduce vascular permeability. An intravenous 5% solution of 5-10 ml is injected. It is better to add this dose to 5% glucose solution for infusion.

After stabilization of systolic A.D. not lower than 110 mm. mercury column, euphiline administration is shown (relaxes bronchial muscles, reduces resistance of blood vessels and pressure in the pulmonary artery system, increases renal blood flow and diuresis). It is injected intravenously in a dose of 5-10 ml. 2.4% solution together with 20 ml of 20% glucose slowly (within 4-6 minutes). Availability of euphylline possibility to reduce A.D. allows to recommend its use only after stabilization of hemodynamics.

4) Immune response suppression. Emergency intravenous administration of glucocorticosteroids is most effective for this purpose. Preference should be given to dexamethasone (dexazone, dexaven) and hydrocortisone (sol-cortef). Dexamethasone has much greater anti-inflammatory and antihistamine effects than prednisolone, it does not cause sodium and water retention in the body, which makes it a drug of choice in oedematous syndromes, in particular swelling of the brain. It is administered intravenously in a dose of 8-12 mg (1.0 ml ampoule contains 4 mg of dexamethasone), diluting a single dose of 10.0 ml. 5% glucose (glucose solution of any concentration can be used). If there is no effect, a single dose is repeated after 15-20 minutes. Hydrocortisone hemisuccinate or sol-cortef is injected in a dose of 100-500 mg (depending on the severity of the condition) intravenously, dissolved immediately before injection into 10.0 ml. of warm (35-37оС) water for injection. In the absence of these drugs, prednisolone is administered in a single dose of 60-90 mg, or methylpredates in a dose of 80-120 mg, or urbasone in a dose of 250-500 mg. The frequency of injection is similar to that described for dexmatazone.

5) Neutralization of BAS. Unfortunately, this direction is implemented only by administration of antihistamines, because drugs for complex neutralization of BAS for parenteral administration are not currently available. Of antihistamines, preference should be given to tavegil (clamastine), which, unlike other antihistamines reduces capillary permeability and is an effective anti-edema agent. Tavegil is administered 2.0 ml (2 mg) intravenously in 10.0 ml. 5% glucose or physiological solution. Repeated injections are possible after 12 hours. For children, a single dose of tavegil is 1 mg (1.0 ml). If there is no tavegil, dimedrol (1% - 1.0 intramuscular), pipolphene (2.5% - 1.0 intravenously), suprastrastin (2% - 1.0 intravenously) may be injected. Special attention should be paid to calcium preparations (calcium chloride and calcium gluconate). At one time, calcium chloride was the main drug used in allergy, however, the mechanism of its anti-allergic effect is still unclear. At the same time, it is well known in practice that the effect of antihistamines is improved when used together with calcium preparations. Therefore, in case of anaphylactic shock, intravenous administration of calcium chloride together with antihistamines should be used. As for the mechanism of antiallergic effect of calcium preparations, recently there was evidence that extracellular calcium causes increased utilization of its cells in the suppressor series with an increase in their population and increases the suppression of immune response. Probably, its anti-allergic effect is connected with this fact. One more mechanism of calcium salts action should be remembered: they excite the sympathetic nervous system and increase adrenaline secretion in adrenal glands. Thus, calcium chloride or calcium gluconate is most shown in combination with antihistamine drugs in shock II degree. Chloride or calcium gluconate is administered strictly intravenously slowly 10.0 ml. 10% solution.

6) Correction of metabolic acidosis. This is traditionally a difficult task, especially in conditions of impaired microcirculation during shock. The most effective way to treat acidosis is to restore hemodynamics with adequate infusion therapy. It is effective for correction of the metabolic component of cocarboxylase CODD disorders at a dose of 250 mg. intravenously at 6 hour intervals. What is especially important is that cocarboxylase corrects intracellular acidosis (Crew J., 1979; Metsler D., 1980; Mashkovsky M. D.) and the use of cocarboxylase does not require strict control over the parameters of CUB. Thus, cocarboxylase in the initial dose of 250 mg should become an obligatory component of anaphylactic shock treatment. Other drugs used for acidosis correction (4% or 8.4% solution of sodium bicarbonate, 3.66% solution of trisamine) should be used under control of CBS indices in intensive care unit.

7) Correction of oedema and spastic syndromes. In conditions of application of the above mentioned medications, especially large enough doses of glucocor-ticosteroids, there is no need for additional prescriptions for correction of spastic syndrome. If necessary, additional spsmolytics (aminophylline, bricanil, no-spa, papaverine) may be administered. If there is an edema syndrome (cerebral edema, pulmonary edema, laryngeal edema, etc.), infusion therapy is carried out by the method of forced diuresis of the so-called dehydration type. In this case, infusion is preceded by the introduction of saluretics (Lasix) and if necessary, osmotics (Mannitol). Taking into account the natural losses of fluid (perspiration, intestines) 20.0 ml. per 1 kg. of weight per hour, with the method of forced diuresis of dehydration type, the volume of infusions in 1 hour must exactly match the amount of isolated 1 hour of urine.

However, it should be recalled once again that this technique should be implemented only by specialists in the intensive care unit with appropriate control (DIC, DEC, electrolytes, hourly diuresis, blood coagulation system). General practitioner should remember to administer 20 mg of lasix (furosemide) intravenously or intramuscularly (2.0 ml. 1% solution) and 20.0 ml. 40% of glucose (osmotic effect) in the presence of oedema syndrome and induce resuscitation.

8) Resuscitation measures. These are, first of all, intubation or tracheostomy and transfer to artificial lung ventilation, which are implemented in the intensive care unit. Before the arrival of intensive care specialists - air duct and ventilation in a bag or mouth; if necessary - indirect heart massage.

Treatment of Lyell Syndrome

First of all, it should be emphasized that the treatment of Lyell syndrome should be comprehensive, taking into account the pathogenetic points described earlier. The directions of syndrome treatment are as follows:

• Creation of conditions for treatment.
• Restriction of contact with the allergen.
• Antihypoxic protection of the CNS and pain management.
• Detoxification therapy with correction of hypovolemia, hemodynamics, microcirculatory disorders and thrombohemorrhagic syndrome.
• Immune response suppression, antihistamines.
• Antibacterial therapy in the presence of extensive erosions.
• Local treatment.

1. Creation of conditions for treatment. The patient should be on an anti-bedsore mattress or in a hammock-type bed, under a framework that provides sterile conditions. In case of extensive lesions of the mucous membranes of the gastrointestinal tract and the inability to eat independently, you can not use the introduction of food through the probe - a transition to a full parenteral nutrition is recommended. In this case, it should be taken into account that a full parenteral nutrition should include a mandatory minimum, which is 1 kg of body weight per day: water - 30 ml; protein - 0,7 g; carbohydrates - 2,0 g; fats - 2,0 g; sodium - 1,0 mmol; potassium - 0,7 mmol; calcium - 0,11 mmol; magnesium - 0,04 mmol; iron - 1,0 mmol; manganese - 0.6 mmol; zinc - 0.3 mmol; copper - 0.07 mmol; chlorine - 1.3 mmol; phosphorus - 0.15 mmol; fluorine - 0.7 mmol; iodine - 0.015 mmol; thiamine - 0.02 mg; riboflavin - 0.03 mg; nicotinic acid - 0.2 mg; pyridoxine - 0.03 mg; folic acid - 3.0 µg; cyanco-balamin - 0.03 µg; pantothenic acid - 0.2 mg; biotin - 5.0 µg; ascorbic acid - 0.5 mg; retinol - 10.0 µg; ergocalciferol - 0.04 µg; vitamin K - 2.0 µg; alpha-tocopherol - 1.5 µg.

Nutrition is a very important stage, which creates the basis for the success of all therapy, so the attention of the attending physician should be constant. It is necessary to remember that it is not enough to administer only amino acid solutions, fat emulsions and carbohydrate solutions. They should be supplemented with mineral substances with water and fat-soluble vitamins in accordance with this obligatory minimum. The need for an emphasis on nutrition is due to the lack of such an emphasis in most intensive care guidelines.

Since patients with Lyell syndrome are expected to undergo massive infusion therapy (including parenteral nutrition), they are shown the catheterization of central veins (more often - subclinical).

2. Restricting contact with an allergen. Cancellation of drugs that triggered the syndrome, hypoallergenic diet, alkaline drinking, enterosorbents (polyfepan, enterodesis, activated carbon), enzyme preparations, mucous, enveloping decoctions.

3. Anesthesia and antihypoxic protection. This direction corresponds to that described for anaphylactic shock (except Trendelenburg).

Seduxene and sodium oxybutyrate in the described dosages have sufficient analgesic effect. If additional analgesia is required, preference should be given to tilidine (valoron), which can be used in the form of drops (children one drop per year of life, adults - 20 drops 4 times a day), capsules, candles, subcutaneous.

4. Detoxification therapy with correction of hypovolemia, hemodynamics, microcirculatory disorders and thrombohemorrhagic syndrome. Intensive control, described in the section of anaphylactic shock treatment, is mandatory. Detoxification therapy should be complex (crystalloid and colloidal solutions in the ratio of 2:1). Disintoxication therapy should be based on 5% glucose solution, trisol or Ringer's solution, rheopoliglyukin, 10% albumin solution. Disintoxication is carried out according to rehydration type of forced diuresis, the meaning of which is that taking into account natural losses (perspiration, intestines), the amount of injected fluid in 1 hour should be 10-20 ml. more than the amount of urine in 1 hour. This technique allows to effectively correct hypovolemia, hemodynamic and microcirculatory disorders. An important component of detoxification and pathogenetic therapy is the use of albumin under the control of protein metabolism, because hypoproteinemia is a mandatory companion of Lyell syndrome due to large losses of protein by erosive surfaces.

Control of electrolytes and BEC is essential in infusion therapy, as these disorders are at the heart of the disease pathogenesis and their correction is crucial. In order to correct electrolyte and CBD disorders, it is recommended to use not pure 5% glucose, but glucose-potassium-insulin solution (solution of Sodi-Polares or polarizing mixture), Labori solution, lactasol, cocarboxylase according to the method described in the section of anaphylactic shock treatment, as well as trisamine and sodium bicarbonate. Intravenous administration of panangin, potassium chloride is also shown.

If there is no effect from detoxification therapy during the first day, at the end of the day or at the beginning of the next day, plasmapheresis is shown.

It is obligatory to include heparin in the therapy complex at the rate of daily dose of 400-500 ED/kg with the interval between single injections not exceeding 4 hours under the obligatory control of the blood coagulation system.

The use of trental at the rate of 0.6 mg per 1 kg of weight per hour is shown. Daily dose for a person in the West of 70 kg calculated by this method will be: 0.6 mg x 70 x 24 = 1008 mg or 1 g per day. This dose is diluted in 500.0 ml 5% glucose and injected drip slowly for 24 hours.

5. Immune response suppression, antihistamines. Glucocorticosteroids are a mandatory component of Lyell syndrome treatment, however, a number of authors (J. B. Sneddon, D. MacC. Jakson, 1984) question their effectiveness. The drug of choice is celestone (betamethasone) in a dose of 17 to 250 mg/kg per day. The single dose is diluted in 20.0 ml of isotonic sodium chloride solution with intravenous injection or in 200.0 ml with drip injection. Repeated injections after 12 hours. In the absence of celestone, the immunosuppression options described in the treatment section of anaphylactic shock are used. The dosage and methods of administration of antihistamines and calcium preparations correspond to those described in anaphylactic shock.

Against the background of glucocorticosteroid therapy it is shown the use of proteolysis inhibitors (trasilol, pride, counterbalance). The daily dosage of Tracylol and Gordox is 25 000 - 30 000 CIE per 1 kg of weight (the dosage of counterkal is 10 times less). One KIE (kallikrein inhibiting unit) corresponds to the previous designations for these drugs AE and ED. Single doses of proteolysis inhibitors are administered intravenously at intervals not exceeding 3 hours. It should be emphasized that proteolysis inhibitors should be used in Lyell syndrome against glucocorticosteroids, because these drugs have an allergizing effect.

6. Antibiotic therapy. Preference should be given to cephalosporins of the third (cefotaxime, ceftriaxone, ceftazidime, etc.) and especially of the fourth (cephometasol, cephpiron, etc.). ) generations, as along with high bactericidal antistafilococcal and antistreptococcal activity, typical for cephalosporins of the first and second generations, they are active against Escherichia, klebsilliilli, proteins and other gram-negative bacteria, and also show high activity against almost all anaerobes and bacteroids. Preparations of cephalosporins group are injected intravenously or intramuscularly at intervals of 8-12 hours. Daily dose for children is 50-100 mg/kg. For adults, a single dose of 1-2 g.

7. Local treatment. The most optimal open method of treatment with the use of clinetron (bed for the treatment of burned patients on a hovercraft with adjustable temperature) or the installation of a series of ATU (aerotherapy unit), which allows to avoid additional manipulations and drugs. If it is not possible to use these devices, the patient is placed under a sterile tent and used aerosol applications of glucocorticosteroids, keratoplastics, rosehip oil or sea buckthorn, not irritating antiseptics. To improve the healing processes of erosive surfaces, parenteral application of actovagin or solkolceryl is also shown. This treatment is better performed in a burn center.

In the development of hepatic, renal, hepatic-renal insufficiency, comatose condition, appropriate treatment programs in the intensive care unit.

Treatment of Stevens-Johnson Syndrome

The treatment of Stevens-Johnson's syndrome is similar to that described for Lyell's syndrome, adjusted for the clinical picture and the severity of the current.

Treatment of Queen's Laryngeal Edema

Allergen contact restriction, antihypoxic protection of the CNS (except for Trendelenburg), immune response suppression, BAS neutralization are carried out according to the recommendations described in the corresponding sections of anaphylactic shock treatment. Parenteral and local adrenaline administration in the form of an aerosol is shown in case of swelling of Quinke. Diuretics must be used: Lasix for adults 40 mg intravenously, if necessary, repeated administration of the same dose after an hour (for children 1-2 mg/kg/day); mannitol (mannitol) - 0.5 - 1.5 g/kg intravenously, dissolved in 5% glucose solution.

Stridorotic breathing, diffuse cyanosis, participation in the breathing of auxiliary muscles, seizures and consciousness disorders are indications for tracheotomy or intubation.

Treatment of asthmatic status

Any classification is not an end in itself, but a reason for action. This fully applies to the differentiation of the stages of AS, because intensive care must be directed to the pathogenetic dominant characteristic of each stage of AS.

The patient must be hospitalized in the intensive care unit for treatment.

The first stage of AC. The main pathogenetic components of this stage are bronchoconstriction associated with the blockade of betaadrenergic receptors or resistance to the purine derivatives of methylxanthins, severe hypoxia and impaired drainage as an initial stage of respiratory obturation. Emergency measures, in this regard, should be aimed at removal of bronchoconstriction, compensation of hypoxia and restoration of drainage function of bronchi. At this stage, it is especially important to find out whether the bronchoconstriction is due to the use of sympathomimetics or resistance to methylxanthins. The exact answer to this question lies in the basis of the effective treatment of the first stage of AC, since the use of methylxanthins in "ricochet" syndrome due to the use of sympathomimetics and vice versa, allows to effectively treat bronchospasm and prevent further progression of AC. For this purpose, we present the most commonly used in the treatment of BA sympathomimetics and methylxanthins.

Sympathomimetics (adrenomimetics, beta-2-agonists): salbutamol (salamol, salgim, saltos, sterineb salamol), salmeterol (salmeter), hexoprenaline (gyniprol), isoprenaline, clenbuterol, orcyprenaline, terbutaline (ayronil sediko), bricanil, bricanil turbuhaler), fenoterol (berotek, berotek H, partusisten), formoterol (oxis turbuhaler), berodual, bambooterol, volmax, ephedrine, epinephrine.

Methylxanthins: euphillin (aminophylline), diprophylline, pentoxyphillin, theophylline (theostat, theotard), theopeck, theodur, theo-24, uniphylline, theoplus, etiphylline, euphilong, retafillin.

Nowadays, beta-2-agonists are used more often to treat BA. In this case, to relieve bronchospasm shows intravenous administration of euphylline (aminophylline) in an initial dose of 5-6 mg / kg. In case of absence of the effect after 1-2 hours repeated administration in a dose of 0.6-1.0 mg/kg. Daily dose should not exceed 2.0 g. Euphillin should be injected slowly (4-6 minutes) or drip in both cases by diluting in glucose. If the doctor is convinced that bronchoconstriction is not associated with taking beta-2-agonists and is a result of resistance to methylxanthins, the drug of choice is terbutaline (bricanil). The drug is injected subcutaneously into the deltoid lateral region of 0.25 mg, with no effect repeated in the same dose after 15-30 minutes. The next injection of terbutaline may take place not earlier than in 4 hours. Terbutaline may be inhaled twice at 1 minute intervals between the first and second inhalations. The repeated session of inhalation is only in 4-6 hours.

Glucocorticosteroids, which are used in all stages of AC, are still the drugs № 1 in AC. Chuchalin A. D. (1997) recommends hydrocortisone in the initial dose of 600-1200 mg/day or pulse therapy with methyipredom (1000 mg single dose) in case of extremely severe condition of the patient with rapidly developing generalized bronchoconstriction. Our experience shows a good efficacy of the glucocorticosteroid injection regimen described in the section "Immune response suppression" of anaphylactic shock treatment, where dexamethasone is given priority. Moreover, in case of application of beta-2-agonists as the cause of AC, one should always think about the possibility of hypokalemia.

Simultaneously with the use of glucocorticosteroids and bronchodilators start infusion therapy with crystals and colloids, because tachypnoe leads to a pronounced hypohydration, violation of rheology, acid-alkaline and electrolyte balance, blood thickening, which results in a characteristic for AS polycithemia. Infusion therapy is also a reliable means of normalizing the drainage function of the bronchi. Infusion therapy is carried out according to the methods and drugs described in the "Detoxification therapy" section of Lyell syndrome treatment.

Compensation for hypoxia provides oxygen therapy and use of antihypoxants in accordance with the methods and drugs described in the section "Antihypoxic Protection of CNS" of anaphylactic shock treatment. Additional justification of antihypoxant use is high cost of breathing at AC, which sharply worsens the patient's condition.

The basis for restoration of bronchial drainage function is adequate infusion therapy in combination with mucolytics. One of the most effective, but, unfortunately, forgotten mucolytics is sodium iodide. A 10% solution of 5-10 ml. intravenously is used. You can use 1-3% solution of potassium iodide 3-5 times a day with a tablespoon and drink plenty of warm water. Among modern mucolytics preference should be given to ambroxol and acetylcysteine (ACE). Ambroxol can be used intravenously, intramuscularly, subcutaneously in a daily dose of 1.2-1.6 mg/kg with an interval of 8 hours between single injections. Acetylcysteine (ACE) is administered intramuscularly to adults 300 mg once a day; to children 150 mg once a day; to infants 10-15 mg/kg 2 times a day. Vibrating massage is important in the complex of measures to improve drainage. Vibrating massage is performed by vibrating (shaking) movements of the hands applied to the chest, alternately in all its departments with the execution of this procedure in different body positions every 30-40 minutes (A.P. Silber, 1984). The vibrating massage disrupts the internal connections and contact of the sputum with the airway wall, which makes the sputum more fluid and promotes better evacuation. When performing a vibratory massage, remember that excessive shaking can provoke bronchospasm, pneumothorax, and pulmonary bleeding, so in AS it should be carried out against the background of glucocorticosteroids and bronchodilators, without excessive effort. In the absence of coughing, all procedures associated with the improvement of sputum should end with sucking it out of the upper respiratory tract.

In the absence of the effect of the described procedures and medications during the day, but before the appearance of the "silent lung" shows hemosorption.

The second stage of AC. Its main pathogenetic components are airway obstruction, right ventricular insufficiency, combined hypoxia, metabolic disorders. At the same time, it should be clearly understood that the leading here is airway obstruction, and all the other components are only its derivative. In this regard, the main efforts should be focused on the elimination of respiratory obstruction and the only effective way here is lavage (washing) of the bronchial tree with the help of therapeutic bronchoscopy. Bronchoscopy with an injection bronchoscope with a needle embedded in it through which a large stream of oxygen is supplied is especially shown in AC. With the help of such a bronchoscopy it is possible to thoroughly perform lavage and release small and medium bronchi.

Naturally, bronchoscopy and lavage are only components of the Compound Lex therapy described above (first stage AC). The peculiarities of the second stage drug therapy are the increase of glucocortico steroids dose by 1.5-2 times and the correction of metabolic acidosis under the control of parameters of BS and electrolytes, as well as the blood aggregation state under the control of the coagulation system.

The third stage of AS - hypoxic coma requires transfer to artificial ventilation of the lungs and maximum activity of therapeutic tactics described in the two previous stages.

Prevention of allergic diseases

There are two directions in prevention: 1) prevention of allergic diseases; 2) prevention of aggravation of allergic diseases.

Prevention of allergic diseases

It should be quite clear that clinical manifestations of allergic disease, regardless of the age at which it occurred, are the result of various causes and factors, which may begin to have an effect even in the womb. Our clinical experience allows us to assert that most allergic diseases of adults take their origins in childhood. Therefore, the most realistic prevention of allergic diseases is to identify the risk factors for their development and neutralize this risk, starting with pregnancy and early childhood. Some of these factors are known, but most of them have yet to be studied. It should also be emphasized that the prevention of allergic diseases, as well as any other - is not so much a medical as a social problem.

Risk factors during pregnancy

1. work during pregnancy in the production shops of chemical plants;
2. viral infections transmitted during pregnancy;
3. treatment during pregnancy with penicillin antibiotics;
4. excessive consumption of products with high allergenic activity (eggs, milk, seafood, chocolate, etc.) during pregnancy;
5. use of progesterone in pregnant women with the threat of miscarriage;
6. late toxicosis of pregnancy;
7. fetal hypoxia in the presence of a pregnant woman with chronic pathology of bronchopulmonary system and cardiovascular pathology;
8. active and passive smoking.

Prophylaxis measures are related to the impact on the presented risk factors: cessation of work in production workshops of "harmful" production during pregnancy, prevention of viral infections, prescription of antibiotics in pregnant women only for life indications, the diet of pregnant women taking into account food allergenicity; elimination of smoking, both active and passive; adequate treatment of complications of pregnancy, prevention of fetal hypoxia based on full and timely correction of respiratory and hemodynamic insufficiency in the presence of the following products.

Risk factors associated with childbirth

First of all, they should include birth trauma and asphyxia of newborns, which in 48% and 45% respectively are accompanied by allergic pathology. In this connection, proper labor management, prevention of birth trauma and asphyxia are the most effective ways of prevention of allergic diseases. At the same time, all variants of perinatal and neonatal pathology can also be attributed to risk factors for allergic diseases.

Early childhood risk factors

• Breastfeeding stops up to 6 months;
• birth of the child during flowering of plants (spring, summer);
• early complementary feeding with mixtures based on cow's milk and hydrolyzates of cow's milk whey proteins;
• inclusion of highly allergenic products (cow's milk, eggs, citrus, etc.) into the diet of breastfeeding mothers;
• early (up to 6 months) application in addition to solid food;
• treatment with antibiotics, especially penicillin series;
• digestive disorders, especially dysbacteriosis;
• frequent acute respiratory viral respiratory infections;
• passive smoking;
• environmental disruption.

Among prevention measures, full breastfeeding should be especially recommended, meaning breastfeeding for over 6 months. According to our data, about 50% of mothers stop breastfeeding for up to 3 months. Therefore, insistence on promoting full breastfeeding is one of the most effective measures to prevent allergic diseases.

Childhood risk factors

• environmental disadvantage;
• frequent ODSs;
• antibiotic treatment;
• digestive disorders (dysbacteriosis);
• vaccination against immunocompromising background;
• living in damp and poorly ventilated rooms;
• Preferential use in diet of dishes based on cow's milk (porridge, etc.);
• excessive consumption of highly allergenic products;
• emotional lability;
• passive smoking;
• fluffy toys;
• pets (cats, guinea pigs, etc.).

The role of vaccination as a risk factor for allergic diseases in children should be emphasized in particular. The fact is that the use of vaccine antigens in case of inability of the immune system to respond to them, at best, will not give the planned protective effect, but more often leads to the transformation of the immune response to an allergic disease. Given the almost total vaccination of children, this factor becomes one of the main risk factors for allergic diseases. Only the determination of immunocomprometry, correction of detected disorders (preventive immunocorrection), and then vaccination can help overcome this impasse.

Adult risk factors

Most of these risk factors also occur in adults. Factors related to professional activity (chemical industry, microbiological industry, production of paints and varnishes, rubber industry, medicine production, detergents and washing powders, cosmetics, pesticides, etc.) are added to them.

Thus, the prevention of allergic diseases is a whole complex of social and medical measures aimed at improving the environment, the formation of a healthy lifestyle and neutralization of risk factors, starting from the intrauterine period.

At the same time, the greatest likelihood of allergic diseases in cases where risk factors affect the risk groups - people who are sensitive to allergic diseases. We have already noted that the problem of identifying allergic risk groups has not yet been adequately developed, and the main place in the formation of risk groups is now given to heredity. The role of heredity in the formation of allergic diseases is reflected in the "Genealogical and family history" section "General principles of allergic disease diagnostics". However, heredity is not the only criterion for inclusion in the risk group. As it has already been mentioned, allergic diseases usually occur against the background of compromised immune system, therefore, immunocompromise, along with heredity, we also refer to the criteria for identification of allergic disease risk groups. From laboratory criteria of allergic immunocomprometry, we offer the determination of the number of eosinophils, basophils, monocytes, IgA, IgG, IgE.

The most realistic selection of risk groups is possible in screening studies of children and adults in the conditions of the immunological service.

Prevention of complications of allergic diseases

Prevention in this direction is primarily related to attempts to stop or limit contact with allergens and is described in the section "General principles of allergy treatment" (immunocorrection, exposure to other causes and conditions that contribute to the formation of allergic diseases, the elimination of the causal factor).

The prevention of urgent conditions associated with allergic diseases is based on the allergological anamnesis collected from each patient, especially if parenteral administration of medicines and diagnostics is planned in the medical care program.

By: Dr. Gary Stadtmauer