Vakula D. Optimization ways of complicated atopic dermatitis forms development diagnosis, treatment, and prevention in children at early age

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0821U102516

Applicant for

Specialization

  • 228 - Педіатрія

25-10-2021

Specialized Academic Board

ДФ 17.600.037

Zaporizhzhya State Medical University

Essay

30 healthy and 85 children with atopic dermatitis, divided into groups based on the morbidity, were examined.The role of the atopy family medical history, the feeding character in the first year, occupational hazards at mothers’ work and negative living conditions was detected. The main clinical variants of complicated activation of potentially pathogenic atopic dermatitis microbiome types were systematized: scaly spots with a raised or scalloped border, double counters, a clear form, separated; a coalesced squaw-erythematous rash with large lamellarscaly crust in contrast to hyperemia with denominated dryness, hyperlinearity and fissures in the areas of physiologic bends; plaque psoriasis-like rash, often on a hairy part of the head and/or dispersedthroughout the body; induration areas, the round-shaped rashes from 1 to 5 cm in diameter combining vesicules, oozing lesion, maceration and denominated hyperemia; common form. Levels oftransepidermalwater loss levels is a qualitative diagnostic criteria of a physical barrier(p<0.05). A significant difference was found in the rs9290927 genotype distribution of Claudin-1 intercellular junctions gene among children with atopic dermatitis and controls (χ2=6.26, р<0,05). For the children with clinical signs of complicated atopic dermatitis, the activation of opportunistic pathogenic microflora was proved by detecting changes in рН(рН<5.52 та рН>5.87, р<0.001, Sp–86%, Se – 86,3%) and microbiological study. The growth of C.albicans, C.nonalbicans, H.compactum, Asp.nidulans was found among these children, the microbiological method sensitivity for detecting the mycotic contamination was 21,4 %. Based on the results of the immune status, children with complicated forms were divided into 2 subgroups: the IIIa - children who had a clinical remission, IIIb– children, whose treatment could not achieve the clinical remission during observation time (6-12 months). It was detected lower complement component of С3, CD3+, CD56+,the total amount of IgA, IgM, IgG and higher levels of TLR-4 in the IIIb subgroup (p<0,05). Conducted on the grounds of the certain CD3+, CD56+ levels and С3 component level, a ROC-analysis made it possible to predict uncontrolled course of the disease (AUC = 0.935,Se – 80.0 %, Sp – 84.62 %, р <0,0001) and (AUC = 0,870, Se - 75 %, Sp - 75 %,р <0.0001). The strong positive connection of severity in the I, II and III groups with the ІL-13 levels (r = + 0.73; р <0.05) was found. The IIIbchildren had a decrease ofІL-13 and ІЛ-4 levels comparing with groups I, II, IIIa (р <0.05).The severity had a direct connection of average strength with the ІL-1βlevels (r=+0. 67, р<0.05). The ІL-12 levels increased with the severity (p<0.05) and were higher in the IIIb subgroup comparing to the IIIa(p<0.05). The correlation of the ІL-12 levels with TLR-4 indicators in the IIIb group showed a direct weak strength (r = +0.29, р<0.05). An algorithm of managing patients with complicated atopic dermatitis severity was offered, which includes a physical examination, identifying the morphological changes, the skin pH-metry and bacteriological study. Using emollients at the first signs of atopy is an effective way to prevent the disease progression (p<0.05). The exjuvantibustherapy by antimicrobial drugs agents for infants with activation signs of opportunistic pathogenic flora and рН skin changes is effective and makes it possible to restore skin acidity on 10-14 treatment day (р<0.001). The role of the Claudin-1 gene and its connection with the formation was first studied in Ukraine. The strategy of differentiated approaches was firstly developed to diagnose, treat and prevent the development of complicated atopic dermatitis forms in infants. The skin barrier features their clinical variants were highlighted. The skin pH-metry diagnostic role at activating of pathogenic microflora was proved. The scientific data on immunologic changes in complicated atopic dermatitis forms were deepened. The factors that influence the development of complicated uncontrolled disease course were offered. The method of diagnostics of secondary infection was offered: estimating the clinical variants and pH-metry of the skin. The main clinical variants of complicated activation of the potentially pathogenic atopic dermatitis microbiome types were systematized. The way to predict the development of lingering uncontrolled atopic dermatitis course for infants was discovered by creating the ROC-curve of CD3+, CD56+ and C3 levels.The algorithm for managing patients with complicated atopic dermatitis forms was created and implemented.

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