The search for personalized methods of diagnosis and treatment of atopic dermatitis due to its high prevalence, heterogeneity of pathogenesis and resistance to standard treatment in modern dermatology is of high medical and social importance. Endotoxin of gram-negative bacterial is one of the major regulators that affects the development of allergy and atopic dermatitis. Determining the effect of endotoxin and its receptor polymorphism on immunopathogenesis, the risk of developing atopic dermatitis can greatly increase the effectiveness of diagnosis and treatment of this disease.
Stage 1 included a cross-sectional study analyzing clinical indicators: age, gender, severity and quality of life criteria, age characteristics of the onset of AD development, hereditary parameters, comorbidities, frequency of exacerbations depending on season, frequency of exacerbations under the influence of trigger factors, frequency of concomitants allergic diseases, frequency of sensitization to the main allergens according to allergoamnesis; instrumental: detection of sensitization to major mixtures of allergens and food according to skin prick tests; immunological: determination of TNF-α, IL-2, γ-IF, IL-4, IL-5, IL-10, TGF-β levels in peripheral blood.
In stage 2, the study of the association of endotoxin receptor gene polymorphism (C-159-CD14; A-896G-TLR-4, 1196 C> T-TLR-4) with determination of cytokine profile (TNF-α, IL-2, γ -IF, IL-4, IL-5, IL-10, TGF-β) in the total population studied and depending on the distribution of exogenous and endogenous phenotype of AD.
In stage 3, an open-label, controlled, randomized clinical trial was conducted in 6 parallel groups for 28 days, with the inclusion of 37 AD patients. To study the effect of probiotic (Lactobacillus acidophilus (LA-5), Bifidobacterium animalis subsp. Lactis (ВВ-12)) on the severity of the disease, quality of life and immune parameters with regard to CC and CT genotypes, all patients were divided into 3 groups for both exogenous and endogenous AD. The first group selected patients with the genotype CC (C-159T), who received standard therapy (ointment fluticasone propionate 0.005% - 2 times a day, loco bite of the ripe - 2 times a day) and probiotic (Lactobacillus acidophilus (LA-5), Bifidobacterium animalis subsp. Lactis (ВВ-12)- 1 capsule 2 times a day day). The second group included patients with the CC genotype who received only standard therapy. The third group was represented by patients with the genotype TT (C-159T) who received standard therapy and a probiotic. The SCORAD and DLQI indices were evaluated at the time of randomization (day 0) at days 14 and 28. IL-4, IL-5, IL-10, TGF-β cytokines were determined on the day of randomization and on day 28.
Results and conclusions. The dissertation is devoted to the improvement of personalized diagnostics and treatment of adult patients with atopic dermatitis by studying clinical, instrumental, immunological criteria of stratification for exogenous and endogenous form and determination of the risk of developing the disease and endotoxin-mediated immune pathogenesis.
The results showed that the incidence of exogenous atopic dermatitis is 35,4 %, endogenous – 64,6 %. Additional clinical criteria for stratification of endogenous and exogenous atopic dermatitis may be patients’ age and onset of disease. Patients' age of endogenous atopic dermatitis was significantly greater (p=0,028) compared to exogenous ones. The onset of AD in patients with endogenous form in the age group of 31 to 60 years was reported in 25,8 %, which was significantly different (P=0,034) compared with exogenous (5,8 %).
Immunological studies have shown that chronic inflammation is associated with a significant (P<0,05) increase in peripheral blood tumor necrosis factor α, mediators of the 1/2 immune response (interferon-γ, interleukin-2, 4, 5) and a decrease in suppressive cytokines (interleukin-10, transforming growth factor-β) compared to control. The endogenous form of atopic dermatitis, unlike exogenous, is characterized by a significant (P<0,05) increase in the level of tumor necrosis factor α in the peripheral blood compared with the control group. However, there are no significant (P>0,05) differences in the concentration of type 1/2 cytokines and suppressive mediators between exogenous and endogenous atopic dermatitis.
