Atopic dermatitis is a chronic allergic inflammatory skin disease accompanied by rashes and itching. It is a pathology of allergic nature with a severe course accompanied by skin lesions. The causes of this disease in children are hidden in a genetic predisposition, and thus, the illness is chronic, with periodic exacerbations occurring in response to specific and non-specific irritants and allergens. Atopic dermatitis represents a local manifestation of disorders of the immune system. Treatment involves an integrated approach mainly aimed at normalizing the body’s functions. Atopic dermatitis is practically the most frequent skin disease in childhood and adolescence; many adults also have this disease. According to the statistics, four out of five children of preschool age have manifestations of atopic dermatitis, although not all of them have a chronic form. It is impossible to protect a child from environmental influences, which means that factors exacerbate atopic dermatitis. Hence, careful attention to the child’s body and preventative measures are extremely important.

General Background of the Disease

Atopic dermatitis is the most common allergic skin lesion caused by a combination of hereditary factors. These factors account for about 20 – 30% of these diseases. The term atopy determines a hereditary predisposition to a group of allergic illnesses developing because of contact with different groups of exogenous allergens. As a medical term, atopy means oddity in Latin. Dr. A. F Coca first introduced it at the beginning of the XXth century to designate different hereditary variations of human hypersensitivity with the formation of antibodies to allergens. Its application is not accidental because, in most cases, it is impossible to find a real cause of atopic dermatitis. By large-scale studies conducted in the middle of the XXth century, around 10% of the world’s population suffered from atopy, including allergic rhinitis, bronchial asthma, and other diseases. It has been established that with atopy, there is frequently imposition of certain atopic manifestations on others. Atopic dermatitis usually develops in early childhood and is characterized by a chronic course with occasional exacerbations in response to specific and non-specific irritants and allergens. Skin rashes represent the main symptom of atopic dermatitis, accompanied by severe itching that can result in psychological and physical maladjustment of patients. The nature of foci and their localization have specific characteristics in different age groups.

Mechanisms of the Disease Formation

As noted above, atopic dermatitis is characterized by a genetic predisposition. Most researchers believe atopic dermatitis should be attributed to multifactorial illnesses with a polygenic type of inheritance with a threshold effect. A threshold value is achieved with the combination of certain environmental factors and genetic defects, and the clinical picture of the disease appears. Many phenotypically healthy people have a high risk of developing allergic diseases in negative environmental conditions. With pronounced hereditary defects, the minor impact of environmental factors is enough for the predisposition to allergic reactions realized in the form of illness. Contrariwise, aggressive environmental factors with minimal genetic defects can result in the rapid formation of atopic dermatitis. Attainments of fundamental scientific research in molecular medicine have resulted in understanding core biological defects occurring in patients with atopic dermatitis. In modern literature, many observations indicate the relationship between allergic diseases in parents or relatives and allergic manifestations in children. If both parents of the child have an atopic illness, the risk of atopic dermatitis is 50% to 80%. If the maternal line burdens heredity, the risk of developing the atopic disease is 30% to 50%. These days, about 20 candidate genes responsible for the formation of atopic dermatitis have been described. In the XXIth century, 13 new polymorphisms have been described in connection with the formation of allergic skin lesions located mainly on chromosomes 1q, 3q, and 17q. Considering the attainments of modern molecular medicine, several groups of candidate genes can be distinguished as the ones controlling the possibility of the development of atopic dermatitis. The first group includes genes predisposing to atopy (the increase in total IgE). The second group is genes, which affect the IgE response. The third group includes genes of hyperresponsiveness of the skin not dependent on atopy. The fourth group consists of genes causing inflammation by exposure to inflammatory cytokines independently of IgE. Predisposition to atopy is connected with loci 1q23-q25, 13q14.1, 11q12-q13, 6p21.2-p12, 5q33.2, and 5q32. Following Gell and Coombs’s classification, the most important, but not the only, mechanism for the formation of atopic dermatitis consists of allergic reactions of the first group. Whatever types of allergic reactions participate in the formation of the illness, the major element in the pathogenesis of atopic dermatitis is the production of proinflammatory cytokines and chemokines responsible for the development of chronic allergic inflammation. It is primarily IL-4 and a receptor for IL-4, IL-5, IL-6, IL-10, IL-13, IL-18, TNF-alpha, TGF-beta1, IFN-gamma, and GM-CSF. For a full allergic reaction, it is necessary to form chemokines responsible for the chemotaxis of basophils, monocytes, induction and attraction of eosinophils to the site of the allergic reaction, and release of the contents of eosinophil granules. The skin of patients with atopic dermatitis is extremely vulnerable and dry. Changes in the gene that encode the protein filaggrin are among the mechanisms of predisposition to changes in the skin’s barrier function. People with mutations in the gene encoding filaggrin are prone to the formation of atopic eczema and ichthyosis vulgaris. Filaggrin represents a protective protein commonly expressed in skin cells. It acts as a physical barrier preventing exposure to hazardous substances from the environment. It reduces lipid synthesis and disrupts the formation of the epidermal barrier, which is why allergens can easily penetrate the epidermal layer. There is a hypothesis that the inheritance of several defective filaggrin genes weakens the physical barrier, thus reducing its effectiveness and increasing the risk of developing allergic skin lesions. In addition, genetic predisposition to the excessive formation of immunoglobulins responsible for immediate-type hypersensitivity reactions is assumed. A complex of genetic factors causes a predisposition to allergic illnesses. They play a highly important role in developing atopic dermatitis and include congenital disorders of digestive functions in the form of enteropathies, leading to the pathological assimilation of food and endogenous intoxication of the organism. Similar conditions are accompanied by dysbiosis, which violates the gallbladder’s motility, contributing to the synthesis of autoantigens. A result of these processes is the formation of toxic antigens, absorption of components of the food not inherent in the body, development of dysfunction of receptors of the central nervous system, peripheral receptors, and neuroendocrine disorders, as well as the formation of autoantibodies with further development of an auto-allergic reaction with the damage of tissues. According to this theory, food allergens play a lesser role with age. Skin damage becomes an independent process characterized by a chronic course; it is not always connected with the insensitiveness of certain foods. At the same time, the mechanisms of an atopic allergic reaction undergo significant changes, and its manifestation can be associated with other provoking factors. They may include physical stimuli, inhalation allergens, microbial agents, and chemical allergens. It can be concluded that the theory of genetic conditionality and the immune mechanism of the launch of the pathological process is the main one. Hypotheses concerning other mechanisms of the development of atopic dermatitis are still the subject of debate among researchers.

Clinical Manifestations

There still needs to be a generally accepted classification of atopic dermatitis and objective methods of instrumental and laboratory diagnostics. The diagnosis is established on the ground of clinical manifestations, including typical skin lesions and their localization. Clinical manifestations of atopic dermatitis in children usually appear as an exudative skin lesion during the first year of life. In most cases, the limbs’ neck, face, and extensor surfaces suffer. There is staging in the types of skin lesions in patients with atopic dermatitis. It is proposed to distinguish exudative, erythematous-squamous, and lichenoid forms of atopic dermatitis. The exudative form is characterized by skin swelling, redness, blisters, pimples, soaking, and erosion. Initially, the first manifestations appear on the face; they are frequently symmetrical and are accompanied by severe itching. Gradually, the process spreads to other skin areas; bubbles open, forming a large erosive surface covered with crusts. The scalp, forehead, and cheeks are primarily affected, and similar changes may occur in the natural folds like axillary, elbow, and buttock areas. When there is an erythematous-squamous form of the disease, epidermodermal papules appear, accompanied by severe itching and scratching in children with dry skin. With the prevalence of the lichenoid form in the clinical picture of the disease, there is lichenification and infiltration of the skin on the background of moderate edema and erythema. There is usually severe dryness of the skin and signs of lichenification like strengthening and thickening of the skin pattern. This process is concentrated in natural folds. Epidermodermal papules serve as the main element in this form of the disease. Children experience dry skin, itching, and peeling. As the process progresses, hyperpigmentation and cracks occur at the site of inflammation.

Diagnostic Criteria for Atopic Dermatitis

According to most experts, the diagnosis of atopic dermatitis is based on clinical signs. It is connected with no laboratory or other criteria that would immediately verify the illness. A diagnostic standard proposed by J. M. Hanifin and G. Rajka identifies 4 main and more than 20 additional criteria. Verification of the diagnosis requires at least three criteria from both groups. In 1994, these criteria were revised in Norway to minimize signs. Nonetheless, these criteria are not widely applied in the daily work of pediatricians. The criteria developed by experts in the United Kingdom and presented as the Childhood Atopic Eczema Consensus Document in December 2007 are popular now. Atopic dermatitis can be diagnosed when the child has itchy skin plus three or more other symptoms. Additional symptoms include:

• The presence of dermatitis in the flexion surface of the limbs involving skin folds or the presence of dermatitis on cheeks and extensor surfaces of limbs in children under 18 months.
• The presence of allergic rhinitis or asthma.
• Common dry skin in the last 12 months.
• Others.

The specificity of this set of criteria amounts to 96%, while sensitivity is at the level of 85%. In such a way, diagnosis of this disease is grounded on main clinical characteristics, including dermatitis with typical localization and common dryness and itching of the skin. When there is a concomitant allergic lesion of the respiratory tract, such as bronchial asthma or allergic rhinitis with a similar atopic mechanism, it can be assumed that skin manifestations have a similar immune defect. Such factors as a positive effect of elimination-burdened heredity of atopic diseases and direct or indirect signs that indicate a relationship between exacerbation of dermatitis with non-infectious allergens are of great diagnostic importance.

Laboratory and Special Diagnostic Methods

Examination of the level of allergen-specific and total IgE is significant in patients with atopic dermatitis. It is particularly important in patients with food allergies manifested in atopic dermatitis. Determination of IgE-specific antibodies allows identifying major non-infectious allergens causing exacerbation of atopic dermatitis. Nevertheless, it is necessary to consider that absence of IgE antibodies does not exclude the atopic nature of the illness. The test’s false negative results are frequently revealed in children during their first two or three years of life. Besides, inhalation of allergens can be causal for children with atopic dermatitis. The appearance of this disease in children after contact with pets, fur, or woolen products indicates the possibility of sensitization to non-infectious allergens. Sometimes, it is enough to exclude pets from the child’s environment or change clothes for all clinical manifestations of atopic dermatitis to decrease or disappear in the patient. Thus, it is necessary to pay particular attention to diagnosing sensitizing factors. An attempt to identify sensitization in patients with atopic dermatitis by applying the definition of IgG antibodies is considered pathogenetically unreasonable. Antibodies of the IgG group belong to blocking antibodies without a diagnostic value. In recent years, great attention has been paid to diagnosing fungal and bacterial sensitization in patients with atopic dermatitis. The determination of class E antibodies to Staphylococcus aureus and its exotoxins in patients with this disease has allowed a group of experts to suggest the pathogenetic importance of this factor. Besides, it is impossible to totally resolve disputes relating to the value of determining IgE antibodies to particular fungal allergens. Malassezia furfur, mainly Pityrosporum orbicular and Pityrosporum ovale, is detected most frequently in patients with atopic dermatitis. This yeast fungus lives on the skin of all people; however, its significance and role in the pathogenesis of atopic dermatitis are still unclear. One more method of diagnosis of non-infectious sensitization in patients with atopic dermatitis includes skin tests. A skin testing method is rather effective in diagnosing pollen and household sensitize. Nonetheless, this examination method could be more efficient for diagnosing food sensitization. The high frequency of false-positive and false-negative results suggests the necessity to conduct elimination-provocation tests that are particularly significant for selecting an individual diet. A double-blind, placebo-controlled test is a standard for diagnosing food allergies. The patient is injected with a tested product disguised into the food. Besides, the patient receives a placebo. At the same time, the child and parents do not know what exactly is introduced into the diet. The conduction of provocations following the above scheme is performed only for research purposes, and clinical manifestations of atopic dermatitis are recorded.

Treatment of Atopic Dermatitis

A modern strategy for the treatment of the disease includes several areas. They are eliminating causative factors, local external therapy, and systemic therapy. In children in the first year of life who suffer from atopic dermatitis, the onset of the disease is frequently connected with food allergies. With age, the connection of atopic dermatitis with a food allergen is not always traced, and thus, the significance of strict elimination in patients with atopic dermatitis of the older age group is questioned. The major issue, in this case, is associated with insufficiently efficient laboratory methods for diagnosing food allergies that are widely applied in practice. It is necessary to emphasize the necessity to identify all causal factors that result in the formation of atopic dermatitis. It applies to elimination diets in patients with food allergies manifested in atopic dermatitis. Normalization of the diet of the breastfeeding mother and amino-acid mixtures allow attaining nutritional elimination in the majority of children during their first year of life. Sensitization in children is possible by eating any food. An attempt at partial elimination is ineffective and frequently harmful. In addition to food allergens, elimination measures should include pollen and household allergens. Eliminating contact between a sick child with pets, products made from wool, fur, and certain synthetic fabrics can considerably reduce clinical manifestations of the disease. Therefore, a hypoallergenic diet and lifestyle are necessary for attaining remission of atopic dermatitis in children. Moreover, this disease requires special skin care. The major purpose of general skin care is to humidify the skin and restore its barrier function. Regular use of emollients and moisturizers is highly important for the child’s skin. Emulsifiers in the composition of moisturizers impact the skin’s barrier function, while ceramide-containing lipid components reduce transepidermal water loss through the skin. Moisturizers make atopic skin less sensitive to irritants.

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