Targeted NGS in Diagnostics of Genodermatosis Characterized by the Epidermolysis Bullosa Symptom Complex in 268 Russian Children.

The pathogenic variants of genes encoding proteins, participating in the formation and functioning of epidermis and dermo-epidermal junctions, create a large variety of clinical phenotypes from: small localized to severe generalized dermatitis, as well as early, or even, prenatal death due to extensive epidermis loss. The diagnostic panel in this study was developed for the purposes of identifying these pathogenic genetic variants in 268 Russian children, who possessed the epidermolysis bullosa symptom complex in a selection of 247 families. This panel included the targeted areas of 33 genes, which are genetic variants that can lead to the development of the phenotype mentioned above. The usage of next generation sequencing allowed the revelation of 192 various altered alleles (of which 109 alleles were novel, i.e., had not been described previously). In addition, it allowed the definition of the genetic variants that are both typical for most of the examined children and for the separate ethnic groups inhabiting modern Russia. We found that the most characteristic mutations for the Dargin and Chechen ethnic groups are the c.3577del deletion in the COL7A1 gene and the c.2488G>A missense mutation in the COL17A1 gene, respectively. In addition, the study of haplotypes of microsatellite markers, which we managed to conduct in the Dargin population, confirmed the presence of the founder effect.

Observational study of pimecrolimus 1% cream for prevention of transcutaneous sensitization in children with atopic dermatitis during their first year of life.

Introduction: Epidermal barrier dysfunction in children with atopic dermatitis can cause transcutaneous sensitization to allergens and allergic diseases. We evaluated the effectiveness of an early-intervention algorithm for atopic dermatitis treatment, utilizing pimecrolimus for long-term maintenance therapy, in reducing transcutaneous sensitization in infants. Method: This was a single-center cohort observational study that enrolled children aged 1-4 months with family history of allergic diseases, moderate-to-severe atopic dermatitis, and sensitization to ≥ 1 of the investigated allergens. Patients who sought medical attention at atopic dermatitis onset (within 10 days) were group 1 "baseline therapy with topical glucocorticoids with subsequent transition to pimecrolimus as maintenance therapy"; patients who sought medical attention later were group 2 "baseline and maintenance therapy with topical glucocorticoids, without subsequent use of pimecrolimus". Sensitization class and level of allergen-specific immunoglobulin E were determined at baseline, and 6 and 12 months of age. Atopic dermatitis severity was evaluated using the Eczema Area and Severity Index score at baseline and 6, 9 and 12 months of age. Results: Fifty-six and 52 patients were enrolled in groups 1 and 2, respectively. Compared with group 2, group 1 demonstrated a lower level of sensitization to cow's milk protein, egg white and house dust mite allergen at 6 and 12 months of age, and a more pronounced decrease in atopic dermatitis severity at 6, 9 and 12 months of age. No adverse events occurred. Discussion: The pimecrolimus-containing algorithm was effective in treating atopic dermatitis and prophylaxis of early forms of allergic diseases in infants. Trial registration: https://clinicaltrials.gov/ NCT04900948, retrospectively registered, 25 May 2021.