Causes of atopic dermatitis in children

The causes of atopic dermatitis in children are varied. The occurrence of the disease is significantly influenced by gender, climatic and geographical features, technogenic level, state of the economy and quality of life of the population.

Due to its high prevalence and steady increase in incidence among children, atopic dermatitis occupies one of the leading places in the overall structure of allergic diseases. According to the results of studies conducted in 155 clinical centers around the world (ISAAC program - International study of asthma and allergy in childhood), the frequency of atopic dermatitis among children ranges from 10 to 46%. Epidemiological studies under the ISAAC program (1989-1995) showed that in Russia and the CIS countries, the prevalence of atopic dermatitis in children ranges from 5.2 to 15.5%. Further studies revealed a direct dependence of the prevalence of atopic dermatitis on the degree and nature of environmental pollution.

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Quality of life

Atopic dermatitis, maintaining its clinical manifestations for many years, has an adverse effect on the physical and mental development of children, changes their usual way of life, contributes to the formation of psychosomatic disorders, leads to social maladjustment, difficulties in choosing a profession and creating a family. At the same time, relationships in the family of sick children are often disrupted: labor losses of parents increase, problems arise in the formation of the child's environment, material costs associated with arranging life, observing the regime and diet, etc. increase. Suffering and inconvenience to patients are caused not only by pathological skin processes and itching, but also by restrictions in daily activity (physical, social, professional), which sharply reduces the quality of life.

Risk factors and causes of atopic dermatitis in children

Atopic dermatitis develops, as a rule, in individuals with a genetic predisposition to atopy under the influence of external and internal environmental factors. Among the risk factors for the development of atopic dermatitis in children, the leading role is played by endogenous factors (heredity, atopy, skin hyperreactivity), which, in combination with various exogenous factors, lead to the clinical manifestation of the disease.

Causes of atopic dermatitis in children (Kaznacheeva L.F., 2002)

Uncontrollable causes	Conditionally controlled causes	Controllable causes (factors formed in family conditions)
Genetic predisposition to atopy. Climatic and geographical factors	Antenatal. Perinatal. Unfavorable environmental conditions in the area of residence	Dietary (feeding characteristics, family food traditions, etc.). Household (living conditions). Factors caused by: violation of skin care rules; presence of foci of chronic infection; unfavorable psychological climate; violation of vaccination rules

Endogenous causes of atopic dermatitis in children

80% of children suffering from atopic dermatitis have a family history of allergies (neurodermatitis, food allergies, hay fever, bronchial asthma, recurrent allergic reactions). Moreover, the connection with atopic diseases is most often traced through the mother's line (60-70%), less often - through the father's line (18-22%). At present, only the polygenic nature of the inheritance of atopy has been established. If both parents have atopic diseases, the risk of developing atopic dermatitis in a child is 60-80%, in one of the parents - 45-56%. The risk of developing atopic dermatitis in children whose parents are healthy reaches 10-20%.

In addition to genetically determined IgE-dependent skin inflammation, the atopic genotype may be due to non-immune genetic determinants, such as increased synthesis of proinflammatory substances by mast cells. Such selective induction (excitation) of mast cells is accompanied by hyperreactivity of the skin, which may ultimately become the main implementing factor of the disease. There is also a possibility of an acquired breakdown of the immune response (similar to the atopic genotype) or spontaneous mutation as a result of exposure to various stressful situations (diseases, chemical and physical agents, psychological stress, etc.).

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Exogenous causes of atopic dermatitis in children

Among the exogenous causes of atopic dermatitis in children, triggers (causal factors) and factors that aggravate the action of triggers are distinguished. Triggers can be substances of an allergenic nature (food, household, pollen, etc.) and non-allergenic factors (psychoemotional stress, changes in the meteorological situation, etc.).

Depending on the age of the children, various etiological causes of atopic dermatitis in children act as triggers or relevant factors ("culprits") of atopic skin inflammation. Thus, in young children, in 80-90% of cases, the disease occurs due to food allergies. According to the literature, the degree of sensitizing potential of various products can be high, medium or weak, but in most cases, food allergies at an early age are provoked by proteins of cow's milk, cereals, eggs, fish and soy.

Why does the skin become the target organ of an allergic reaction, and atopic dermatitis is the earliest clinical marker of atopy in young children? Probably, the anatomical and physiological characteristics of children of this age can predispose to the development of allergic reactions, namely:

• huge resorptive surface of the intestine;
• reduced activity of a number of digestive enzymes (lipase, disaccharidases, amylase, proteases, trypsin, etc.);
• the unique structure of the skin, subcutaneous fat layer and blood vessels (extremely thin layer of epidermis, richly vascularized dermis itself, a large number of elastic fibers, loose subcutaneous fat layer);
• low production of diamine oxidase (histaminase), arylsulfatase A and B, phospholipase E, which are contained in eosinophils and participate in the inactivation of allergy mediators;
• vegetative imbalance with insufficient sympathicotonia (dominance of cholinergic processes);
• predominance of production of mineralocorticoids over glucocorticoids;
• decreased production of IgA and its secretory component - IgAS;
• age-related dysfunction of the adrenergic cyclic nucleotide system: decreased synthesis of adenylate cyclase and cAMP, prostaglandins;
• a unique structural structure of the plasma membrane bilayer: increased content of arachidonic acid (a precursor of prostaglandins), leukotrienes, thromboxane and an associated increase in the level of platelet activating factor.

It is obvious that with an unjustifiably massive antigen load and hereditary predisposition, these age-related characteristics can lead to the development of an atopic disease.

As children grow, food allergies gradually lose their dominant role, and at the age of 3-7 years, triggers of allergic inflammation are household (synthetic detergents, library dust), mite (Dermatophagoides Farinae and D. Pteronissinus), pollen (cereal grasses, trees and weeds) allergens. In children aged 5-7 years, sensitization to epidermal allergens (dog, rabbit, cat, sheep hair, etc.) is formed, and their impact through damaged skin can be quite intense.

A special group of causes of atopic dermatitis in children are bacterial, fungal, and vaccine allergens, which usually act in association with other allergens, potentiating individual links of allergic inflammation.

In recent years, many authors have noted the enormous importance of the enterotoxin superantigen Staphylococcus aureus in the development and course of atopic dermatitis, colonization of which is observed in almost 90% of patients. Secretion of toxin superantigens by staphylococci stimulates the production of inflammation mediators by T cells and macrophages, which exacerbates or maintains skin inflammation. Local production of staphylococcal enterotoxin on the skin surface can cause IgE-mediated release of histamine from mast cells, thus triggering the mechanism of atopic inflammation.

In approximately 1/3 of patients, the cause of atopic dermatitis in children is mold and yeast fungi - Alternaria, Aspergillus, Mucor, Candida, Penicillium, Cladosporium, under the influence of which a superficial fungal infection usually develops. It is believed that, in addition to the infection itself, an allergic reaction of an immediate or delayed type to the components of the fungus can play a role in maintaining atopic inflammation in this case.

In young children, atopic dermatitis in children is sometimes caused by a viral infection called Herpes simplex.

Sometimes the trigger for the clinical manifestation of the disease may be vaccination (especially with live vaccines) carried out without taking into account the clinical and immunological status and appropriate prevention.

In some cases, the causes of atopic dermatitis in children can be medications, most often antibiotics (penicillins, macrolides), sulfonamides, vitamins, acetylsalicylic acid (aspirin), metamizole sodium (analgin), etc.

Non-allergenic causes of atopic dermatitis in children include psycho-emotional stress, sudden changes in weather conditions, tobacco smoke, food additives, etc. However, the mechanisms of their participation in the development of atopic dermatitis remain not fully understood.

The group of exogenous causes of atopic dermatitis in children, which aggravate the action of triggers, includes climatic and geographical zones with extreme temperatures and increased insolation, anthropogenic pollution of the environment, exposure to xenobiotics (industrial pollution, pesticides, household chemicals, medicines, etc.).

Factors such as violation of diet, dietary regimen and skin care rules are important in maintaining allergic inflammation, especially in infants and young children.

Among the household causes of atopic dermatitis in children that increase the impact of triggers, the following can be distinguished: poor home hygiene (dry air, low humidity, “collectors” of house dust and mites, etc.), synthetic detergents, keeping pets in the apartment (dogs, cats, rabbits, birds, fish), passive smoking.

All this leads to increased dryness of the skin and mucous membranes, a decrease in their bactericidal properties, inhibition of phagocytosis and increased permeability to allergens.

Chronic infections in the family (microbial proteins can selectively stimulate the production of T-helpers type 2), psychological conflicts (form astheno-neurotic reactions, hyperreactivity syndrome), disorders of the central and autonomic nervous system, somatic diseases (lungs, gastrointestinal tract, kidneys), psychosomatic and metabolic disorders also have a persistent triggering effect.

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Pathogenesis of atopic dermatitis in children

In the multifactorial pathogenesis of atopic dermatitis, immune disorders play a leading role. It is generally recognized that the development of the disease is based on a genetically determined feature of the immune response, characterized by the predominance of the activity of T-helpers type 2, which leads to hyperproduction of total IgE and specific IgE in response to environmental allergens.

The differences in the immune response between the atopic and non-atopic (normal) types are determined by the function of T-cell subpopulations that contain the corresponding pools of memory T-cells. The memory T-cell population, when constantly stimulated by an antigen, can direct the T-cell (CD4+) response of the body along the pathway of producing T-helpers of type 1 (Th1) or type 2 (Th2). The first pathway is typical for individuals without atopy, the second - for atopy. In patients with atopic dermatitis, the predominance of Th2 activity is accompanied by a high level of interleukins (IL-4 and IL-5), which induce the production of total IgE, against the background of reduced production of γ-interferon.

The immune trigger for atopic dermatitis is the interaction of antigens with specific antibodies on the surface of mast cells, which in children (especially at an early age) are concentrated in large quantities in the dermis and subcutaneous fat layer. In turn, non-immune relevant factors enhance allergic inflammation through non-specific initiation of the synthesis and release of pro-inflammatory allergy mediators, such as histamine, neuropeptides, and cytokines.

As a result of the violation of the integrity of biological membranes, antigens penetrate into the internal environment of the body -> presentation of antigens by macrophages on the molecule of the major histocompatibility complex class II (MHC) and the subsequent expression of antigens by Langerhans cells, keratinocytes, endothelium and leukocytes -> local activation of T-lymphocytes with an increase in the process of differentiation of T-helpers (CD4+) along the Th2-like pathway -> activation of the synthesis and secretion of proinflammatory cytokines (IL-2, IL-4, IL-5, TNF-a, TNF-y, MCSF) -> increased production of total IgE and specific IgE with further fixation of Fc fragments of the latter to specific receptors on mast cells and basophils -> increased number of dendritic and mast cells in the dermis -> disruption of prostaglandin metabolism -> colonization of S. aureus and their production of superantigens -> implementation allergic inflammation with predominant localization in the skin.

Although immune disorders are of primary importance in the pathogenesis of atopic dermatitis, activation of immunocompetent cells is controlled by neuroimmune interactions whose biochemical substrates are neuropeptides (substance P, neurotensins, calcitoninogen-like peptide) produced by the endings of nerve fibers (C-fibers). In response to various stimuli (extreme temperature, pressure, fear, overexcitation, etc.), neuropeptides are released in C-fibers, resulting in vasodilation, manifested by erythema (axon reflex). The participation of the peptidergic nervous system in the manifestation of atopic dermatitis is due to the anatomical connection between Langerhans cells, blood vessels and C-fibers.

Thus, atopic dermatitis in children has very different causes, so the clinical manifestation of the disease develops as a result of the combined effect on the body of genetic factors, triggers and factors that enhance their effect.