Reshetilo O. Clinical and pathogenetical models and differentiated therapy in atopic dermatitis in children

The thesis is devoted to improving the efficiency of managing children with atopic dermatitis through the development of the differentiated therapeutic approaches depending on the clinical and pathogenetic models of the disease. Taking into account the key role of the epidermal barrier in the pathophysiology of allergodermatosis, we studied the effect of structural and functional disorders of the stratum corneum protein Flg on the course of atopic dermatitis (AD) in children. The frequency and variants of R501X and 2282del4 polymorphism in the Flg gene in children with AD have been established. Under conditions of Flg dysfunction, a study of the dielectric properties of the epidermis was carried out and it was shown that the indicators of skin moisture according to corneometry data can be used as a functional marker of local inflammation (χ2 0.000001; p<0.05), as well as an assessment of AD severity and determination of the therapy effectiveness, which should be taken into account in clinical practice. Restoration of proper skin moisture against a background of differentiated use of emollents is accompanied by regression of clinical manifestations (RRR 0.142). In our work, the role of oxalic acid dysmetabolism was proved and its metabolites excretion features in AD in children were studied. The important clinical sign of AD in the presence of rise of oxalates level in urine and the expired breath condensate is the intensity of itching (χ2 8.3; p=0.004. To correct metabolic changes, the use of a low oxalate diet was proposed. The admnistration of the diet in the complex of therapy was accompanied by positive dynamics of objective and subjective indicators by SCORAD (RRR 0,086) and BRS (RRR 0,333). The study of clinical and anamnestic characteristics, along with the determination of specific molecular genetic and metabolic markers, made it possible to identify separate clinical and pathogenetic models (filaggrin-associated and oxalate-associated) in AD and to propose a therapeutic and diagnostic algorithm, the effectiveness of which has been proven by clinical and laboratory indicators, quality of life index, and also confirmed by the immediate results and follow-up observations.