Features of the Course and Treatment of Atopic Dermatitis Associated with Staphylococcus aureus in Children

The dissertation is dedicated to the study of the clinical and metabolic features of atopic dermatitis (AD) associated with Staphylococcus aureus in early childhood. The research is oriented toward a comprehensive assessment of the role of bacterial colonization of the skin and mucous membranes, the state of the immune system, processes of lipid peroxidation, and the stability of erythrocyte membranes in the pathogenesis and course of the disease. The study analyzes the enzymatic status of blood cells (lymphocytes and thrombocytes) and evaluates the effectiveness of complex therapy, which includes antibacterial and antioxidant components.

The results of the study have shown that AD in children is characterized by high colonization of the skin by St. aureus, significant disturbances in lipid peroxidation processes, and metabolic shifts in blood cells. The severity of these disturbances correlates with the degree of disease severity and the period of its course. The inclusion of preparations with antioxidant activity (sodium thiosulfate and limontar) in complex therapy contributes to a more rapid regression of clinical symptoms and normalization of metabolic parameters.

RELEVANCE OF THE STUDY

In the twenty-first century, allergic pathology remains an urgent problem of medicine. Atopic dermatitis (AD) is one of the most prevalent allergic diseases of childhood and is the most severe among dermatoses, as it manifests in early age, is characterized by a staged course, frequent relapses, is accompanied by involvement of internal organs, and is often complicated by secondary pyogenic infection, which significantly reduces the quality of life of the child [150,152, 169, 176, 5, 11, 153, 158, 14, 12, 13, 15]. However, the complexity of the treatment of patients with AD lies primarily in the fact that it requires a strictly individualized approach.

It is known that the formation and development of AD in children is based on sensitization of the organism to various allergens. Conducted studies show that the majority of children have polyvalent sensitization to food, pollen, fungal, mite, and epidermal allergens [152, 109, 48, 80, 31, 96, 161, 158, 81, 105]. Moreover, in the etiological structure of AD in early childhood, food allergy plays a leading role [80, 5, 92]. In the future, exacerbations of the disease may be caused by contact with mite, fungal, and other allergens, including bacterial ones.

According to data from various authors [152, 176, 31, 93, 96, 45, 46, 65, 101, 105], children with AD exhibit high colonization of the skin, mucous membranes, and various biological secretions with pathogenic microorganisms. As our studies have shown, to date the role of infectious factors, in particular St. aureus, in the onset and subsequent course of AD in early childhood has been insufficiently studied, which complicates the development of adequate therapeutic methods [11, 161,15].

According to contemporary concepts, atopy is regarded as the capacity of the organism for heightened production of IgE in response to various environmental allergens, associated with hereditary predisposition to allergy, T-cell immune response, subsequent development of allergic inflammation, and nonspecific hyperreactivity of organs involved in the allergic process [18, 14, 13, 230,232,233, 254].

The synthesis of IgE, IgG, and other immunoglobulins is the ultimate result of immune reactions in which blood cells, in particular lymphocytes, participate. To date, it has been convincingly demonstrated that lymphocytes are cells that perform not only specialized functions of immune protection but also serve as elements of a unified information system that accurately reflects the state of the organism and the process of its development [181, 104, 187, 29, 1,26, 112]. On the basis of studying the enzymatic status of lymphocytes and thrombocytes, one may assess the adequacy of the immune response to any external influence, including contact with an allergen, the degree of severity and prognosis of the course, and the effectiveness of treatment [187, 112]. The diagnostic and prognostic capabilities of cytochemical analysis of blood cells are virtually limitless [67, 53, 104, 102] and may be successfully employed also in AD. At the same time, the available literature contains only isolated works concerning the study of the enzymatic status of lymphocytes in AD in children [4]. The enzymatic profile of thrombocytes in this pathology has not been studied.

At present, considerable attention is devoted to processes of lipid peroxidation (LPO). This is attributable to the fact that, being an integral part of normal homeostasis, lipid peroxides accumulate as a result of activation of free-radical oxidation processes, substantially alter the structural-functional properties of cellular membranes, and constitute one of the most prevalent causes of their damage [35, 83,22, 70,95].

Damage to membrane cellular structures is a universal pathological process that reflects disruption of metabolic processes in cells in many pathological states, infectious and allergic diseases, and stress, and is closely linked to the level of lipid peroxidation [52, 161, 120, 149, 50, 88, 143, 145, 188, 41, 51, 89, 164, 17, 34, 36, 108, 116,119, 141, 166, 8, 38, 55, 59, 60, 165, 73, 98, 122, 37, 135, 162, 76, 127, 129, 106, 177, 178, 166, 228, 224,205, 218, 253].

A novel original method for determining the stability of erythrocytes to peroxidous hemolysis, proposed by the staff of the Department of Hospital Therapy of the Izhevsk State Medical Academy (patent No. 2102766), makes it possible to quantitatively assess the dynamics of the state of erythrocyte membranes, reflecting the pathological changes occurring in the human organism [6].

Under clinical conditions, the results of studying LPO indicators are sufficiently widely used in diseases of the cardiovascular system [149, 89, 141, 38, 60, 37], lungs [50, 94, 162], gastrointestinal tract [64, 88, 51, 108, 99, 122], and infectious diseases [163, 34, 33, 55, 59, 117, 127, 168] for assessing the severity of the pathological process, monitoring the effectiveness of treatment, and forecasting disease outcomes.

Intensification of peroxidative processes in the organism aggravates T-cell immunodeficiency and leads to the uncoupling of oxidation and phosphorylation in blood cells, which is reflected in the enzymatic status of lymphocytes and thrombocytes.

It is presumed that under the influence of food and other allergens, infectious factors, in particular St. aureus, in early-aged children with AD, activation of lipid peroxidation is observed and metabolism of blood cells is disrupted, which contributes to the chronic course of the disease [3].

One of the directions in the therapy of AD is the modulation of the activity of cells involved in the realization of the immune response. It may be presumed that the functions of immunocompetent cells depend on the state of their energy metabolism; therefore, studying these parameters and their correction becomes a promising direction in the treatment of severe and complicated forms of AD in early childhood.

The objective of the research is to develop an optimal therapeutic strategy based on the study of the clinical and metabolic features of AD associated with St. aureus in children.

To achieve this goal, the following tasks were set: 1. To identify the features of the clinical picture of AD in children at different age periods. 2. To investigate the frequency of colonization of the skin and mucous membranes by St. aureus in children with AD. 3. To study the parameters of the humoral link of immunity in children with AD. 4. To investigate LPO, the stability of erythrocyte membranes to peroxidous hemolysis, and the enzymatic status of blood cells in children with AD during exacerbation and remission. 5. To evaluate the effect of antibacterial and antioxidant therapy on the clinical course and metabolic parameters in children with AD.

SCIENTIFIC NOVELTY.

Bacteriological examination of the skin and mucous membranes in children with AD revealed their high colonization by St. aureus, which determined the necessity of conducting antibacterial therapy. Using ELISA, allergen-specific IgE were determined, and a predominance of high-level sensitization to St. aureus was demonstrated, confirming its important role in the formation of AD.

For the first time, a comprehensive evaluation of LPO, the stability of erythrocyte membranes to peroxidous hemolysis, and the enzymatic status of lymphocytes and thrombocytes in various forms of AD in children was conducted, which made it possible to identify the activation of free-radical oxidation processes and deep metabolic disturbances in blood cells. For the first time, it has been demonstrated that the highest degree of LPO intensification and decreased stability of erythrocyte membranes are characteristic of the period of inflammatory skin manifestations, which are accompanied by a significant decrease in enzymatic activity and disruption of the structure of blood cell populations. For the first time, it has been established that disruption of LPO processes and suppression of dehydrogenases activity of blood cells are of a persistent nature, and their restoration significantly lags behind the onset of clinical remission of AD. During dynamic observation of children, a significant decrease in enzymatic activity of blood cells was noted after 6 months. Correlation relationships between the level of LPO, stability of erythrocyte membranes, and dehydrogenases activity with the severity of AD in children have been identified.

The results obtained from the comprehensive study of LPO indicators, stability of cellular membranes, and enzymatic activity of blood cells make it possible to expand existing concepts of metabolic disturbances in AD.

For the first time, the inclusion of preparations with antioxidant activity (sodium thiosulfate and limontar) in the complex therapy of AD in children has been substantiated.

PRACTICAL SIGNIFICANCE.

The indicators of LPO, stability of erythrocyte membranes, and dehydrogenases activity of blood cells are proposed as an additional criterion for assessing the severity of the pathological process and reflect the establishment of metabolic remission in children with AD. The use of antibacterial preparations in patients with severe and moderate-severe AD allows for a significant reduction of St. aureus colonization of the skin. The inclusion of preparations with antioxidant activity (sodium thiosulfate and limontar) in the complex therapy of children with AD leads to a more rapid regression of symptoms of the late phase of allergic inflammation, normalization of LPO indicators, stability of cellular membranes, and an increase in enzymatic activity of lymphocytes and thrombocytes.

IMPLEMENTATION INTO PRACTICE.

The results of the work have been implemented in the practical activities of the Republican Children's Consultative Polyclinic, departments of the Republican Children's Clinical Hospital, the allergology office of Children's Polyclinic No. 5 of Izhevsk, the sanatorium "Lastochka" of Izhevsk, as well as in the educational process of the Department of Pediatrics of the Izhevsk State Medical Academy.

MAIN PROVISIONS PRESENTED FOR DEFENSE:

1. The course of AD in early childhood is characterized by the specificity of the clinical picture and high colonization of the skin and mucous membranes by St. aureus.

2. AD in children is accompanied by significant disturbances in the LPO system and substantial metabolic shifts in blood cells, the severity of which depends on the degree of disease severity and the period of the disease.

3. Complex basis therapy with the use of antibacterial and antioxidant agents in children with AD contributes to a more rapid reversal of the main clinical manifestations of the disease, significant improvement in LPO indicators and stability of erythrocyte membranes, and an increase in enzymatic activity of blood cells.

VALIDATION OF THE WORK:

The materials of the dissertation were presented at the International Conference "Antibiotics and Antibiotic Resistance at the Threshold of the Twenty-First Century" (Moscow, 2000), the International Conference "Atopic Dermatitis-2000" (Yekaterinburg, 2000), the 111th Medical Congress "Young Scientists of Russia" (Izhevsk, 2000), the 4th Congress of the Russian Association of Allergologists and Clinical Immunologists (RAAKI) "Modern Problems of Allergology, Immunology, and Immunopharmacology" (Moscow, 2001), the II Conference of Young Scientists "Fundamental Sciences and Progress in Clinical Medicine" (Moscow, 2001), the II Inter-University Conference of Young Scientists and Students "Actual Medical and Biological Problems" (Izhevsk, 2002), the III Inter-University Conference of Young Scientists and Students (Izhevsk, 2003), the VIII Congress of Russian Pediatricians "Modern Problems of Preventive Medicine" (Moscow, 2003), and at the joint session of the problem commission of the pediatric faculty and departments of pediatrics, childhood infections with a course of childhood diseases, pediatrics and childhood infections, postgraduate training and advanced training, propaedeutics of childhood diseases with a course of outpatient pediatrics of the Izhevsk State Medical Academy.

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