Atopic dermatitis

Atopic dermatitis is an acute, subacute or chronic recurrent inflammation of the epidermis and dermis, characterized by severe itching, and has a certain age-related dynamics.

The term "atopic dermatitis" was first proposed in 1923 by Subzberger for diseased skin accompanied by increased sensitization to various allergens. Allergic diseases (hay fever, allergic rhinitis, bronchial asthma) are often found in the anamnesis or in close relatives. This definition is conditional and there is no generally accepted definition of atopic dermatitis in the scientific literature, since the term is not applicable to any clearly defined clinical situation, but to a heterogeneous group of patients with chronic superficial inflammation of the skin. Synonyms for atopic dermatitis are atopic eczema, constitutional eczema, allergic dermatitis, neurodermatitis, prurigo Rciibe, exudative-catarrhal diathesis, allergic diathesis, childhood eczema. The variety of terms reflects the phase transformation of skin elements and the chronic relapsing course of the disease.

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Epidemiology

Atopic dermatitis occurs in all countries, in both sexes and in different age categories.

The incidence of atopic diseases is increasing. They affect approximately 5 to 20% of the population, most often manifesting themselves as allergic rhinitis and atopic dermatitis (approximately 50%) and much less often as bronchial asthma. Atopic dermatitis manifests itself in most cases already in infancy, often between 2 and 3 months of life. The disease can also occur in later childhood. According to scientists, atopic dermatitis is the eighth most common dermatose disease in people under 25 years of age. The disease occurs in infancy, early childhood, adolescents and adults. Males are more often ill in infancy and childhood, and women - in late childhood and adulthood. Primary manifestations of atopic dermatitis after puberty are relatively rare.

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Causes atopic dermatitis

Atopic dermatitis primarily affects children in developed countries; at least 5% of children in the United States are affected. Like asthma, it may be associated with a proallergic or proinflammatory T-cell immune response. Such responses are most common in developed countries, which tend to have smaller families, better indoor hygiene, and early vaccination, which protects children from infections and allergens but suppresses the proallergic T-cell response and leads to tolerance.

Atopic dermatitis develops under the influence of environmental factors that provoke immunological, usually allergic (e.g., IgE-mediated) reactions in people with an increased genetic predisposition. Causal factors include food (milk, eggs, soy, wheat, peanuts, fish), inhaled allergens (dust mites, mold, dander) and colonization of Staphylococcus aureus on the skin due to a lack of endogenous antimicrobial peptides. Atopic dermatitis often has a genetic component, so it is familial.

Kaposi's eczema herpetiformis is a common form of herpes simplex that occurs in patients with atopic dermatitis. Typical clusters of blisters form not only at the site of the rash but also on healthy skin. After a few days, the temperature rises and adenopathy develops. The rash is often infected with staphylococcus. Sometimes viremia and infection of internal organs develop, which can lead to death. As with other herpes infections, relapse is possible.

Fungal and non-herpetic viral skin infections, such as warts and molluscum contagiosum, can also complicate atopic dermatitis.

Exogenous (biological, physical and chemical) and endogenous (gastrointestinal tract, nervous system, genetic predisposition, immune disorders) factors participate in the development of atopic dermatitis. The leading role in the pathogenesis of atopic dermatitis belongs to hereditary predisposition. In 70-80% of children with atopic dermatitis, there is a high level of IgE in the serum, which is under the control of the IL-4 gene. If the population risk of developing atopic dermatitis is 11.3%, then in children-probationers it is 44.8%. In patients with atopic dermatitis, familial atopy occurs 3-5 times more often than in healthy people. Mainly, there is a connection with atonic diseases on the mother's side (60-70%), less often - on the father's side (18-22%). It has been established that atopic dermatitis develops in 81% of children if both parents suffer from atopic dermatitis and in 56% when only one parent suffers. According to some scientists, atopic dermatitis is inherited in a polygenic manner.

According to modern views, the most important place in the functioning of the immune system belongs to T-cells with helper activity and a decrease in the number and functional activity of T-suppressors. The immunopathogenesis of atopic dermatitis can be presented as follows: as a result of the violation of the integrity of biological membranes, the penetration of an antigen (bacteria, viruses, chemicals, etc.) into the internal environment of the body occurs and these antigens are recognized by antigen-presenting cells - APC (macrophages, Langerhans cells, keratinocytes and leukocytes), which activate T-lymphocytes, and the process of differentiation of T-helpers of the first and second order is enhanced. The key point is calcineurin (or calcium-dependent phosphatase), under the influence of which the nuclear factor of activated T-lymphocytes is granuloplastinated into the nucleus. As a result, activation of second-order T-helpers occurs, which synthesize and secrete proinflammatory cytokines-interleukins (IL 4, IL 5, IL 13, etc.). IL 4 is the main factor for inducing IgE synthesis. There is also an increase in the production of specific IgE antibodies. Subsequently, with the participation of mast cells, which produce histamine, serotonin, bradykinin, and other biologically active substances, the early phase of the hyperergic reaction develops. Then, in the absence of treatment, the IgE-dependent late phase develops, characterized by infiltration of the skin by T-lymphocytes, determining the chronization of the allergic process.

In the development of atopic dermatitis, great importance is attached to the functional state of the gastrointestinal tract. Dysfunction of the gastrin regulation link has been revealed, consisting in the imperfection of parietal digestion, insufficient activity of enzymes in the processing of chyme, etc. In children of the first year of life, a common cause of atopic dermatitis is the consumption of chicken eggs, proteins, cow's milk, cereals. The course of atopic dermatitis is aggravated by the development of dysbacteriosis due to the uncontrolled use of antibiotics, corticosteroids, the presence of foci of chronic infection, allergic diseases (asthma, rhinitis), dysmetabolic nephropathy, helminthiasis.

The Importance of Inheritance Patterns in Atopic Dermatitis

The inheritance pattern is not yet clear in all details and is not associated with a single gene. The influence of the HLA system is also apparently absent. The probability of the disease for a child with one parent with atopy is estimated at 25-30%. If both parents are atopic, it increases significantly and is 60%. The presence of a polygenic type of inheritance is likely. It is not a specific atopic disease that is inherited, but a predisposition to an atopic reaction of various systems. Approximately 60-70% of patients have a positive family history of atopy. For this reason, careful collection of family and individual anamnesis, taking into account atopic diseases, has diagnostic value for determining atopic dermatitis. In addition to hereditary predisposition, exogenous, individually realized factors also play an important role. Among the environmental factors that provoke atopic diseases of the respiratory tract or intestines, not only inhalation (house dust mites, plant pollen, animal hair) or food (often together with allergic urticaria) allergens are important - such as milk protein, fruits, eggs, fish, preservatives, but also such individual factors as stress or concomitant psychovegetative and psychosomatic disorders.

Vulgar ichthyosis is observed in about 30% of cases, with an even higher frequency of dry skin (asteatosis, sebostasis) with altered lipid content and increased water permeability (impaired barrier function). Many patients have a typical ichthyotic palm with a strongly expressed linear pattern - hyperlinearity. Vitiligo is more common in patients with atopic dermatitis, and alopecia areata in such patients has an unfavorable prognosis (atopic type of alopecia). Also noteworthy, although very rare, is the formation of eye anomalies such as atopic cataract, especially in young people, less often keratoconus. There is a connection with dyshidrosis, dyshidrotic eczema of the palms and urticaria. The connection with migraine is debated, but it is not considered reliably established.

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Risk factors

In recent years, there has been an increase in the incidence of atopic dermatitis. This is apparently due to the frequent use of allergenic foods, vaccination, taking various medications, particularly antibiotics, and environmental pollution.

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Pathogenesis

Atopic dermatitis is a hereditary disease of multifactorial nature with a genetically determined deficiency of the function of T-lymphocyte suppressors, simultaneous partial blockade of beta-adrenergic receptors and B-dependent IgE-globulin mechanism of pathological immune reactions. The main symptom is itching. Skin lesions vary from moderate erythema to severe lichenification. The diagnosis is based on anamnestic and clinical evidence. Moisturizing creams and local glucocorticoids are used in treatment. In addition, it is necessary to avoid allergic and irritating factors.

Atopic dermatitis is characterized by age variability, chronic relapsing course, itchy inflammatory skin lesions with true polymorphism (erythema, papules, vesicles), lichenification; symmetrical topography of rashes, depending on evolutionary dynamics; often combined with functional disorders of the nervous system, immune disorders, atopic lesions of the respiratory organs.

Atopic dermatitis (AD) is IgE-dependent (exogenous 70-80% of cases) or IgE-independent (endogenous in 20-30% of cases) type. IgE-dependent is better studied; IgE-independent atopic dermatitis is idiopathic and without familial predisposition of the disease.

Among dermatological diseases, atopic dermatitis occupies a special place in dermatology due to its unclear etiopathogenesis, chronic course and related therapeutic problems. There are about a hundred designations for this disease in the literature. Unlike English and French literature, in which the concept of "atopic dermatitis" or "atopic eczema" has been established, German sources more often use the terms "atopic eczema", "endogenous eczema", "diffuse neurodermatitis", "atopic neurodermatitis". Such a terminological kaleidoscope complicates the work of practicing doctors and creates confusion in identifying the disease. It is recommended to adhere to two equivalent and unambiguous terms: "atopic dermatitis" and "atopic neurodermatitis", although in English-language manuals on dermatology the name "atopic eczema" is also often used.

The difficulty in applying the term "atopic disease" is that allergic rhinitis, allergic conjunctivitis and allergic bronchial asthma are IgE-mediated immediate-type allergic reactions (type I according to Coombs and Gell), while atopic dermatitis is most likely a complex interaction of several immunological and non-immunological factors, some of which are still unknown. This fact also explains the difficulties with terminology that exist to this day. The term neurodermatitis, proposed by Brocq in 1891, points to a presumed pathogenetic connection with the nervous system, since severe itching was considered a factor provoking the disease. The synonyms constitutional or atopic neurodermatitis used with this name indicate, in particular, the pathogenetic significance of familial or hereditary factors, while the names atopic eczema, endogenous eczema or constitutional eczema are more focused on eczematous rashes.

The immunological theory has attracted more attention, but the events causing the reaction have yet to be identified. Both humoral and cell-mediated immunity are abnormal. IgE appears to be stimulated by specific antigens. It is localized to mast cells and causes them to release inflammatory mediators. Cell-mediated factors are supported by susceptibility to and recurrence of viral infections, including herpes simplex, molluscum contagiosum, and warts. Patients are often resistant to dinitrochlorobenzene sensitization. The presence of decreased T-lymphocyte numbers may indicate a deficiency in the essential T-cell subsets that control immunoglobulin production by B cells and plasma cells so that IgE production levels are high. In addition, phagocytic activity is reduced and chemotaxis of neutrophils and monocytes is impaired. Another factor that supports the immunological basis is the presence of a significant number of staphylococci on both the diseased and healthy skin of patients with atopic dermatitis.

The beta-adrenergic theory is supported by a number of abnormal cutaneous responses. These include exaggerated cutaneous vascular constrictor responses, white dermographism, delayed blanching to cholinergic stimuli, and a paradoxical response to nicotinic acid. Decreased cAMP levels may increase mediator release from mast cells and basophils.

Disorders of humoral immunity

People with a hereditary predisposition to atopy react to contact with environmental substances (allergens) with immediate sensitization. Such sensitization is confirmed by an immediate urticarial reaction during an intracutaneous test. Immunologically, this is an immediate allergic reaction (type I according to Coombs & Gell). A healthy person does not react to contact with such substances found in the environment. However, the essence of atopic dermatitis cannot be reduced to just one such allergic reaction of the atopic organism.

Positive immediate reactions to food and inhalant allergens are detected by skin testing in patients already in early childhood. The percentage of positive skin reactions ranges from 50 to 90%. Patients with allergic bronchial asthma or allergic rhinitis significantly more often have positive intracutaneous reactions to inhalant allergens, in particular house dust, house dust mite (Dermatophagoides pteronyssinus), plant pollen or animal allergens (animal hair and dander). Human dander and sweat proteins can also act as allergens. Although the causal significance of inhalant allergens as provocateurs of atopic dermatitis worsening is not yet completely clear, any dermatologist knows that seasonal exacerbation of allergic rhinitis is accompanied by worsening of skin manifestations, and vice versa. Food allergens (milk protein, fish, flour, fruits, vegetables) also often give positive test reactions, although they do not always coincide with clinical symptoms. In addition, mothers often note the fact that itching and inflammatory skin reactions in their infants are often provoked by certain foods (e.g., milk or citrus fruits). Prospective studies show that feeding the baby with mother's milk, rather than cow's milk, in the first weeks of life has a positive effect on atopic children; therefore, mother's milk is recommended in the first months of life. In addition, external contact with plant pollen can cause inflammatory skin reactions and provoke pollen vulvitis in little girls.

Thus, in general, although the pathogenetic significance of immediate reactions for the development of atopic dermatitis has not yet been fully assessed, a number of data speak in its favor. The corresponding intradermal and in vitro tests (RAST) are also shown, and the test reactions should be considered critically, in conjunction with the overall clinical picture, which may serve as a reason for possible further measures, such as exposure tests or an elimination diet.

IgE determination is currently most often performed using the PRIST method. Most patients with severe atopic dermatitis have elevated serum IgE levels. Increased IgE levels are especially observed with simultaneous manifestations in the respiratory tract (allergic asthma, allergic rhinitis). However, since some individual patients with widespread skin lesions may have normal IgE levels, its determination, except in cases of suspected hyper-IgE syndrome, has no pathognomonic value, especially since serum IgE levels also increase with other inflammatory dermatoses. Therefore, the absence of serum IgE does not mean that there is no atopic dermatitis. It is also noteworthy that elevated IgE levels decrease during disease remissions.

In recent years, modern immunological methods have provided a better understanding of the regulation of IgE formation. Certain cytokines produced by activated T lymphocytes, in particular interleukin-4 (IL-4) and interferon-7 (INF-y), are involved in a complex network of regulatory signals for IgE synthesis by B lymphocytes. Further research in this area could reveal therapeutic implications if overproduction of IgE could be inhibited.

The RAST method provides the physician with a method for proving in vitro the presence of allergen-specific antibodies to the patient's blood serum. This method can demonstrate the presence of IgE antibodies to a number of inhalant and food allergens. In atopic dermatitis, RAST or SAR are positive in a large percentage of cases; these methods can demonstrate the presence of circulating antibodies to environmental allergens that were not covered by the intracutaneous test.

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Disorders of cellular immunity

In patients with atopic dermatitis, in addition to humoral immunity disorders, there is also a weakening of cellular immunity. It is noteworthy that such patients are susceptible to viral, bacterial and fungal skin infections. These infections, on the one hand, occur more often in atopic patients, and on the other hand, are more severe. Eczema verrucatum, eczema molluscatum, eczema coxsaccium, as well as impetigo contagiosa and tinea corporis are known as complications of this kind. In severe atopic dermatitis, a clear decrease in erythrocyte rosette formation, a change in the reaction of T-lymphocytes to mitogens, a decrease in the in vitro stimuliability of lymphocytes with bacterial and mycotic antigens and a decrease in the tendency to contact sensitization (however, with an increased prevalence of contact allergy to nickel), a decrease in the number or activity of natural killer cells have been proven. The severity of the disease also correlates with the decrease in suppressor T-lymphocytes. It is known from practice that patients have a slight tendency to develop contact dermatitis after topical application of medications. Finally, defects in neutrophilic granulocytes (chemotaxis, phagocytosis) and monocytes (chemotaxis) have been proven. Blood eosinophils increase and react more strongly to stress. Apparently, the number of IgE-bearing lymphocytes is also increased. Interpretation of these data is quite complex. The hypothesis is based on the fact that excessive IgE formation in patients with atopic dermatitis is due to the existing, especially in the first three months of life, secretory deficiency of IgA, and it cannot be compensated for due to the deficiency of suppressor T-lymphocytes. In this sense, the underlying defect should be sought in the T-lymphocyte system. It is possible to imagine that as a result of the disruption of T-lymphocyte activity inhibition, inflammatory changes in the skin may spontaneously develop, as occurs with contact allergic dermatitis. The results of the latest studies also support this hypothesis.

IgE-bearing antigen-presenting cells in the epidermis, i.e. Langerhans cells, may also play a significant role in the development of skin changes in atopic dermatitis. It is assumed that antigen-specific IgE molecules bound to the surface of epidermal Langerhans cells via a high-affinity receptor, aeroallergens (house dust mite antigens from the skin surface) and food allergens interact via the bloodstream. They are then presented by Langerhans cells, like other contact allergens, to allergen-specific lymphocytes, which cause an inflammatory allergic reaction of the eczematous type. This new concept of the pathogenesis of atopic dermatitis forms a bridge between the humoral (IgE-mediated) and cellular components of the immune response and is clinically supported by the fact that epicutaneous tests with inhalant allergens (e.g., pollen) in patients with atopic dermatitis, in contrast to healthy individuals, can lead to an eczematous skin reaction in the test area.

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Disorders of the autonomic nervous system

The most well-known is white dermographism, i.e. vasoconstriction after mechanical stress on the skin in its apparently unchanged areas. In addition, after application of nicotinic acid ester, not erythema but anemia due to capillary contraction (white reaction) occurs reactively. Injection of cholinergic pharmacological agents such as acetylcholine also leads to whitening of the skin at the injection site. Of course, white dermographism is not typical for inflamed areas of the skin. The tendency to vascular contraction in such patients also manifests itself at a relatively low temperature of the skin of the fingers and strong contraction of the vessels after exposure to cold. It is not known for sure whether this is a matter of abnormal sensitivity of alpha-adrenergic stimulation of muscle fibers. In this regard, Szentivanzy's theory of beta-adrenergic blockade became known. Inhibition of beta-receptor activity results in a reduced reactive rise in cAMP cells with an increased tendency to form inflammatory mediators. The imbalance between alpha- and beta-adrenergic receptors can probably also explain the increased sensitivity of smooth muscle cells in the area of blood vessels and pilomotors. The absence of cAMP-induced inhibition of antibody synthesis can lead to an increase in their formation. In addition, a common cause may underlie pharmacological and immunobiological disorders.

Sebostasis (asteatosis)

Reduced sebum production is typical for patients with atopic dermatitis. The skin is dry and sensitive, and tends to dry out and itch further with frequent washing and/or showering. This explains the weak tendency of such patients to seborrheic diseases such as acne vulgaris, rosacea or seborrheic eczema. The dryness and sensitivity of the skin are probably also due to disturbances in the formation of epidermal lipids (ceramides) or disturbances in the metabolism of essential fatty acids (deficiency of 8-6-desaturase), which may have immunological consequences. The recommended diet containing γ-linolenic acids is based on abnormalities in the metabolism of essential fatty acids.

Sweating disorders

Such disorders have not been proven with certainty. Rather, there are disorders of sweating. Many patients complain of severe itching when sweating. It is possible that sweating is impeded by disorders in the stratum corneum (hyperkeratosis and parakeratosis), so that sweat, after exiting the excretory ducts of the sweat glands into the surrounding skin, initiates inflammatory reactions (sweating retention syndrome). Sweat also contains IgE and inflammatory mediators and can cause reflex flushing reactions and urticaria.

Climate allergens

So-called climatic allergens have also been considered as causes of atopic dermatitis. In the mountains at an altitude of over 1,500 m above sea level or on the North Sea coast, patients most often feel very well, but the underlying pathophysiological processes are difficult to generalize. In addition to allergological factors, the level of insolation and the state of mental relaxation may be important.

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Neuropsychological factors

They play a very important role. The effect of stress or other psychological factors can be represented through the adenyl cyclase-cAMP system. Patients with atopic dermatitis are often asthenic individuals, have an above-average level of education, are prone to egoism, self-doubt, conflict situations of the "mother-child" type, in which the mother is dominant, suffer from frustration, aggression or suppressed states of fear. The question remains open as to what is primary and what is secondary. However, severely itchy skin manifestations can also participate in the formation of personality and have a sensitive effect, especially in children, on their development and success at school.

Bacteria

Patients with atopic dermatitis are prone to staphylococcal skin lesions and may have elevated serum levels of staphylococcal IgE antibodies. The pathogenetic significance of this fact is unclear, but it should be taken into account when conducting treatment.

In summary, current evidence suggests an immunological basis for atopic dermatitis. Atopy-specific T-helper cells may play a pathogenetic role by producing and releasing cytokines relevant to allergic inflammation, such as IL-4, IL-5, and other factors. Eosinophils are thought to play a major role as effector cells mediating the pathogenetically significant late-phase reaction, which is associated with significant destruction of surrounding tissue. Accordingly, significant preactivation of peripheral blood eosinophils has been found in patients with atopic dermatitis, leading to increased sensitivity of these cells to certain stimuli, such as IL-5. Toxic proteins such as eosinophil cationic protein, contained in the matrix and core of secondary granules of eosinophils, may play an important role in the propagation of the allergic inflammatory process both indirectly and directly, due to their immunomodulatory properties.

Patients with atopic dermatitis have increased levels of "long-lived eosinophils," which have a long decay period in vitro and are less susceptible to apoptosis. Long-term growth in vitro was stimulated by IL-5 and GM-CSF; both mediators are elevated in atopic dermatitis. Long-lived eosinophils may be a characteristic feature of atopic dermatitis, since eosinophils from patients with hypereosinophilic syndrome do not exhibit similar properties in vitro.

The pathogenetic role of eosinophils in atopic dermatitis is confirmed by the detection of proteins contained in their granules in the eczematous skin of patients. Moreover, modern data indicate a significant correlation between disease activity and the accumulation (deposition) of eosinophilic granule contents:

• Serum eosinophilic cationic protein levels were significantly elevated in patients with atopic dermatitis;
• Eosinophil cationic protein levels correlated with disease activity;
• Clinical improvement was associated with both a decrease in clinical disease activity score and a decrease in eosinophil cationic protein levels.

These data clearly indicate that activated eosinophils are involved in the allergic inflammatory process in atopic dermatitis. Therefore, changes in eosinophil activity may be an important criterion for choosing pharmacological agents for the treatment of atopic dermatitis in the future.

The first and main aspect of the pathogenesis of atopic dermatitis is allergic dermatitis. Intradermal or cutaneous administration of various allergens in most patients with atopic dermatitis, having only skin lesions, has yielded 80% positive reactions. The main role in atopic dermatitis is played by the following allergens: aeroallergens (house dust mite, mold, animal hair, pollen), live agents (staphylococci, dermatophytes, pityrosporum orbiculare), contact allergens (aeroallergens, nickel, chromium, insecticides), food allergens. Of all the specific aeroallergens, house dust mite allergens can cause a specific inflammatory reaction in most patients with atopic dermatitis, especially in people over 21 years of age. Food products are important allergens in atopic dermatitis in early childhood.

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Histopathology

The histopathological picture of the disease depends on its type. In the presence of exudative foci in infancy, the same phenomena are found as in allergic contact dermatitis: spongiosis and spongiotic blisters, incipient acanthosis with hyper- and parakeratosis and serum inclusions, as well as a dermal perivascular infiltrate of lymphocytes and histocytes with exocytosis. In lichenified foci, the epidermis is acanthotically thickened by 3-5 times and has keratinization disorders (hyperkeratosis); the papillary body is hypertrophic and penetrated by inflammatory cells (lymphocytes, histiocytes). Also noteworthy is the presence, as in psoriasis, of a large number of mast cells, which is explained by the increased content of histamine in chronic lichenified foci.

Symptoms atopic dermatitis

Atopic dermatitis usually begins in infancy, before 3 months. During the acute phase of the disease, which lasts 1-2 months, red, crusty lesions appear on the face, which spread to the neck, scalp, limbs, and abdomen. During the chronic phase, scratching and friction cause skin lesions (typical lesions are erythematous spots and papules against the background of lichenification). Lesions usually appear in the elbows, popliteal fossa, eyelids, neck, and wrists. Lesions gradually dry out, causing xerosis. In adolescents and adults, the main symptom is intense itching, which intensifies with exposure to allergens, dry air, sweating, stress, and wearing woolen clothing.

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Forms

The following clinical and morphological forms of atopic dermatitis are distinguished: exudative, erythematous-squamous, erythematous-squamous with lichenification, lichenoid and pruriginous. This division of atopic dermatitis is more acceptable for a practicing physician.

The exudative form is more common in infancy. This form is clinically manifested by bright edematous erythema, against the background of which small flat papules and microvesicles are located. In the lesions, pronounced exudation and scaly-crustal layers are noted. The process in the initial period is localized on the face, in the cheek area, then spreads to other areas of varying intensity. A secondary infection often joins.

The erythematous-squamous form is observed in early childhood. The elements of the rash are erythema and scales, which form single or multiple erythematous-squamous lesions. Against this background, single small papules, vesicles, hemorrhagic crusts, excoriations are often present. Subjectively, itching of varying intensity is noted. The lesions are usually localized on the flexor surfaces of the limbs, the anterior and lateral surfaces of the neck, and the back of the hands.

The erythematous-squamous form with lichenification usually occurs in childhood.

In this form, against the background of an erythematous-squamous lesion, there are intensely itchy lichenoid papular rashes. The lesion is lichenified, the skin is dry, covered with small-plate scales, there are hemorrhagic crusts and excoriations. The rash elements are localized in the elbow folds, on the neck, face, in the popliteal fossa. A secondary infection often joins.

The vesicular-crustose form of atopic dermatitis develops in the 3rd-5th month of life and is characterized by the appearance of microvesicles with serous contents against the background of erythema. Microvesicles open with the formation of serous "wells" - point erosions, while intense itching of the affected areas of the skin is noted. The process is most pronounced on the skin of the cheeks, trunk and limbs.

The lichenoid form occurs in adolescence and youth and has distinct foci with pronounced lichenification and infiltration, lichenoid papules with a shiny surface. Hemorrhagic crusts and excoriations are noted on the surface of the lesion. Due to excruciating itching, sleep disturbances, irritability and other neurological disorders are noted. The lesions are localized on the face (around the eyes, eyelids), neck, elbow bends.

The pruriginous form (prurigo Hebra) is characterized by the appearance of isolated itchy papules up to the size of a pea on the upper and lower extremities, in the neck, gluteal-sacral and lumbar regions.

According to the prevalence of the skin process, limited, widespread and diffuse atopic dermatitis are distinguished.

In limited atopic dermatitis (Vidal's lichen), lesions are limited to the elbow or knee folds, the back of the hands or wrists, and the front or back of the neck. Itching is moderate, with rare attacks (see chronic lichen simplex).

In widespread atopic dermatitis, lesions occupy more than 5% of the skin area, the skin pathological process spreads to the limbs, trunk, and head. Dry skin, intense itching, bran-like or fine-plate peeling are noted. In diffuse atopic dermatitis, lesions of the entire skin surface are noted, with the exception of the palms and nasolabial triangle, biopsy itching, and severe dry skin.

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Complications and consequences

They are caused mainly by secondary infections or incompetent therapy (strict diet with secondary manifestations of deficiency, side effects of glucocorticoids). Growth disorders in children with severe atopic dermatitis are reported. In infections, a certain role is played by dysfunction of leukocytes and lymphocytes, as well as the fact that skin manifestations in patients after many months of treatment with external glucocorticoids become more sensitive to infections. Staphylococcus aureus is often detected on the skin of such patients.

Secondary bacterial infection

It is expressed in impetiginization of foci caused by Staphylococcus aureus. Yellow impetiginous crusts on skin manifestations with an unpleasant odor are a typical picture, which together with painful enlargement of the lymph nodes allows for a diagnosis. Furuncles, erysipelode and external otitis are quite rare.

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Secondary viral infections

The impaired barrier function of the skin in such patients makes it more sensitive to viral infections. This applies primarily to infections caused by the herpes simplex virus (eczema herpeticatum). Currently, transmission of the catpox virus is also reported. This disease begins acutely with fever and a corresponding deterioration in the general condition. Numerous vesicles appear on the skin at the same stage of development. Of practical importance is a smear from the bottom of the vesicle to prove the presence of epithelial giant cells (Tzank test). Sometimes the presence of the pathogen must be proven by electron microscopy, negative contrast, immunofluorescence, PCR or viral culture. Viral infections caused by the Molluscum contaginosum virus (eczema molluscatum) or the human papillomavirus (HPV) (eczema verrucatum) are easily diagnosed. In particular, with warts in the paronychia and on the soles of children, atopy should be considered. Coxsackie virus infection in the area of atopic dermatitis (eczema coxsaccium) is very rare.

Secondary fungal infection

Interestingly, it is rare, mainly in adults, more often in the form of dermatomycosis and is observed when more figure-like erythematous-squamous rashes do not pass with appropriate glucocorticoid therapy. Currently, in particular, the pathogenetic role of contact allergy to Malassezia spp in atopic dermatitis of the scalp and occipital region is discussed. Malassezia spp is considered as a cause of deterioration of the condition in atopic dermatitis in this area. The success of local treatment with ketoconazole (nizoral) speaks in favor of this significance.

According to the prevalence of skin lesions, a distinction is made between: localized lesions (limited lesions in the elbow and popliteal folds or on the hands and wrists, perioral lichenification); widespread lesions; universal lesions (erythroderma).

According to severity (severe, moderate, relatively mild), atopic dermatitis is classified based on the prevalence of skin lesions, duration of the disease, frequency of relapses and duration of remissions.

The most important provocative factors that cause exacerbation of atopic dermatitis are dry skin, heat, sweating, cold, physical exercise, temperature changes, infections, allergic contact dermatitis, anxiety, stress, food allergies, aeroallergens, scratching, and concomitant diseases (scabies).

Diagnostics atopic dermatitis

The diagnosis of atopic dermatitis is made on the basis of clinical features. Atopic dermatitis is often difficult to distinguish from other forms of dermatitis (eg, seborrheic eczema, contact dermatitis, nummular eczema, psoriasis), although atopic history and location of lesions suggest the diagnosis. Psoriasis is usually localized on extensor surfaces, may affect the nails, and is characterized by fine-lamellar scaling. Seborrheic eczema most often affects the skin of the face (nasolabial folds, eyebrows, bridge of the nose, scalp). Nummular eczema does not occur in flexural areas, and lichenification is rare. Allergens in atopic dermatitis can be detected by skin testing or by determining IgE-specific antibody levels. Atopic dermatitis may also be accompanied by other skin diseases.

Two groups of diagnostic criteria (primary or mandatory, and additional or secondary signs) have been identified that help in making a diagnosis of atopic dermatitis.

Essential criteria for atopic dermatitis

1. Itching of the skin.
2. Typical morphology and localization of rashes: in childhood - lesions of the skin of the face, extensor areas of the limbs, trunk; in adults - lichenification on the flexor areas of the limbs.
3. History of atopy or hereditary predisposition to atopy.
4. Chronic relapsing course with exacerbations in spring and autumn-winter seasons.

Although the diagnosis of atopic dermatitis seems fairly straightforward, there are borderline cases and some other skin conditions in atopic individuals, so it is important to adhere to the diagnostic criteria above. At least three major and three minor features are required to make the diagnosis.

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Additional signs of atopic dermatitis

Clinical signs

• Xeroderma or ichthyosis
• Follicular keratosis
• Cheilitis
• Darkening of the skin of the eye sockets
• Non-specific dermatitis of the hands and feet
• Keratoconus
• Anterior subcapsular cataract

Immunological signs

• Elevated serum total IgE
• Food intolerance
• Tendency to skin infections

Pathophysiological signs

• White dermographism
• Itching when sweating
• Facial pallor or erythema
• Intolerance to lipid solvents and wool

In 1993, the European Task Force on Atopic Dermatitis developed a scoring system for assessing the severity of the disease: the SCORAD Index.

In atopic dermatitis, diagnostics is primarily aimed at identifying the causal relationship with various allergens that play a leading role in the development of skin inflammation. It is important to collect an allergological anamnesis, including the history of skin lesions, family allergological anamnesis, the presence of atopic respiratory manifestations, concomitant skin diseases, the presence of risk factors in the anamnesis (course of pregnancy and childbirth, feeding patterns, infection in infancy, use of antibacterial drugs in early childhood, concomitant diseases and focal infection foci, drug intolerance). Allergological examination involves skin tests (outside of exacerbation and in the absence of antihistamine therapy) and provocative tests. In the case of a torpid recurrent course of dermatosis and widespread lesions of the skin, specific IgE and IgG 4 antibodies to non-infectious allergens are determined using MAST (multiple allergosorbent test) or PACT (radioallergosorbent test), and other paraclinical and special instrumental studies are also carried out.

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Scheme of examination of patients with atopic dermatitis

Laboratory and instrumental research methods

• Complete blood count
• Blood biochemistry (total protein, bilirubin, ALT, AST, urea, creatinine, fibrinogen, C-reactive protein, glucose)
• General urine analysis
• Immunological examination (IgE, lymphocyte subpopulations)
• Bacteriological examination of feces (for dysbacteriosis)
• Esophagogastroduodenoscopy
• Electrocardiogram
• X-ray examination of the paranasal sinuses

Allergological examination

• Allergic history
• Skin tests with atopic allergens
• Determination of specific IgE antibodies to atopic allergens (MACT, PACT)
• Provocative tests (nasal, conjunctival) - if necessary

Additional research

• Ultrasound of internal organs, pelvis - as indicated
• X-ray examination - as indicated
• Skin biopsy - as indicated

Consultations with specialists

• Allergist
• Therapist (pediatrician)
• Gastroenterologist
• Otolaryngologist
• Neuropsychiatrist
• Endocrinologist

In lichen planus, there are typical purple papules with a shiny surface and an umbilicated depression in the center; the presence of Wickham's mesh in the form of whitish-grayish dots and stripes is characteristic; damage to the mucous membranes is observed.

In patients with Hebra's prurigo, papules are located on the extensor areas of the limbs; the elements are isolated from each other; the lymph nodes are enlarged; there is no history of atopy.

With mycosis fungoides, the foci of lichenification are less pronounced, and there are no remissions in the summer.

Chronic eczema is characterized by polymorphism of rashes, vesicles, weeping, and red dermographism.

Differential diagnosis

Atopic dermatitis must be differentiated from the following diseases: limited neurodermatitis, lichen planus, Hebra's prurigo, mycosis fungoides, chronic eczema.

Limited neurodermatitis (Vidal's lichen) is characterized by the absence of atopy in the anamnesis, onset of the disease in adulthood; no dependence of exacerbations on the action of allergens; localized lesion; the presence of three zones in the lesion: central lichenification, lichenoid papular rashes and a dyschromic zone; concomitant diseases precede skin rashes; the level of total IgE in the blood serum is normal; skin tests are negative.

Treatment atopic dermatitis

The course of atopic dermatitis in children often improves by the age of 5, although exacerbations occur in adolescence and adulthood. The most likely long-term course of the disease is in girls and patients with serious diseases, with early development of the disease, with concomitant rhinitis or asthma. However, even in these patients, who have atopic dermatitis, it completely disappears by the age of 30. Atopic dermatitis can have remote psychological consequences, since children face the problem during adulthood. In patients with a long course of the disease, cataracts may develop by the age of 20-30.

Treatment is usually done at home, but patients with exfoliative dermatitis, panniculitis, or eczema herpetiformis may require hospitalization.

Maintenance treatment of atopic dermatitis

Skin care is primarily carried out by moisturizing. When bathing and washing hands, use warm (not hot) water, and reduce the use of soap, as it dries the skin and can cause irritation. Baths with colloidal compositions help.

Moisturizing oils, petroleum jelly or vegetable oils may help when applied immediately after bathing. An alternative is continuous use of wet dressings for severe lesions. Creams and ointments containing tar should be used to relieve itching.

Antihistamines are used to relieve itching.

Examples include hydroxyzine 25 mg orally 3–4 times daily (children 0.5 mg/kg every 6 hours or 2 mg/kg once daily at bedtime) and diphenhydramine 25–50 mg orally at bedtime. Mild sedating H2 blockers such as loratadine, fexofenadine, and cetirizine may be used, although their efficacy has not yet been fully demonstrated. Doxepin, a tricyclic antidepressant also with H1 and H2 receptor blocking activity, may be used at a dose of 25–50 mg orally at bedtime, but is not recommended for use in children under 12 years of age. Nails should be kept short to minimize excoriation and secondary infection.

Prevention of provoking factors

Exposure to antigens can be reduced by using synthetic fiber pillows and thick mattress covers, and changing bed linens frequently. In addition, upholstered furniture should be replaced, soft toys and carpets removed, and pets removed. Antistaphylococcal antibiotics, not only for topical use (mupirocin, fusidic acid) but also for systemic use (dicloxacillin, cephalexin, erythromycin, all 250 mg 4 times daily), can control S. aureus colonization and are prescribed to patients with severe disease that is resistant to treatment. Significant dietary changes to eliminate reactions to allergenic foods are not required, as this is not an effective measure. Food allergies rarely persist into adulthood.

Glucocorticoids and atopic dermatitis

Glucocorticoids are the mainstay of therapy. Creams or ointments applied twice daily are effective for most patients with mild to moderate disease. Emollients may be used between applications of glucocorticoids and may be mixed with them to reduce the amount of corticosteroid required to cover the affected area. Systemic glucocorticoids (prednisone 60 mg or in children 1 mg/kg orally once daily for 7 to 14 days) are indicated for extensive lesions and resistance to other therapy, but they should be avoided if possible because the disease often recurs and topical treatment is safer. Systemic glucocorticoids should not be given to infants because they may cause adrenal suppression.

Other Treatments for Atopic Dermatitis

Tacrolimus and pimecrolimus - T-lymphocyte inhibitors, effective in the treatment of atopic dermatitis. They should be used when glucocorticoids fail or cause side effects such as skin atrophy, striae formation or adrenal suppression. Tacrolimus and pimecrolimus are applied twice daily, burning and stinging after application are temporary and subside after a few days. Skin redness rarely occurs.

Phototherapy is useful for extensive atopic dermatitis

Natural sun exposure improves the condition of patients. Alternatively, ultraviolet A (UVA) or B (UVB) radiation may be used. UVA therapy with psoralen is indicated for the treatment of extensive atopic dermatitis. Side effects include non-melanocytic skin cancer and lentigines; for this reason, phototherapy with psoralen and UVB radiation is rarely indicated for the treatment of children or adolescents.

Systemic immune modulators that are effective in at least some patients include cyclosporine, gamma interferon, mycophenolate, methotrexate, and azathioprine. All have anti-inflammatory effects and are indicated for patients with atopic dermatitis who have failed to respond to phototherapy.

For herpetiform eczema, acyclovir is prescribed: infants 10-20 mg/kg every 8 hours; older children and adults with moderate forms of the disease 200 mg orally 5 times a day.

Prevention

The main areas of prevention are adherence to a diet, especially for pregnant and nursing mothers, and breastfeeding children. Particular attention should be paid to limiting the impact of inhaled allergens, reducing contact with household chemicals, preventing colds and infectious diseases, and prescribing antibiotics as prescribed.

Genetic counseling; dietary restrictions (dietary measures for children and adults for clinically proven cases for a certain period of time); avoidance of aeroallergens (avoid contact with cats, dogs, horses, cows, pigs; do not have pets; avoid smoking in the house; use hoods in the kitchen; avoid contact with plants that produce pollen); against house dust mites - thorough carpet cleaning and wet cleaning of the apartment; removing carpets and curtains from the bedroom that collect dust; using pillows with polyester filling, frequent washing of bed linen; elimination of sources of dust accumulation, including TV and computer); against dry skin - lubrication of the skin with creams after bathing, bathing oils, humidification of rooms (maintaining relative humidity at about 40%); avoidance of overheating, sweating, heavy physical exercise; avoidance of rough woolen clothing and synthetic fabrics, "impermeable" fabrics; dispensary observation (information for patients with atopic dermatitis and registration of these patients); training of parents of children with atopic dermatitis.

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Forecast

The prognosis for the course of atopic dermatitis and the quality of life of the patient and his family largely depend on the reliable knowledge they receive about the causes of the development of skin rashes, itching, careful adherence to all doctor's recommendations and prevention.

Due to possible secondary infections in young children, the prognosis should be made with caution. In general, the intensity of the disease decreases somewhat after the first year of life. Skin manifestations become less frequent and almost disappear by the age of 30. The relationship with other atopic lesions, such as bronchial asthma and allergic rhinitis, is individual and not entirely clear. Patients who additionally suffer from these diseases report that sometimes with spontaneous improvement of skin manifestations, the condition of the lungs or nose worsens and vice versa.

It is quite difficult to make a forecast in each individual case.

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