[Genetic-morphological peculiarities of response to standard therapy in patients with dyshidrotic eczema of palms and soles].

OBJECTIVE: Introduction: Dyshidrotic eczema of palms and soles (DEPS) is an inflammatory skin disorder that has a multifactorial nature and is characterized by the development of vesical elements with the histological picture of spongiosis and development of intraepidermal vesicles. The aim: Establishment of the features of pathomorphological changes of the epidermis and dermis in patients with manifestations of dyshidrotic lesions of palms and soles with different genotypic variants of the C646G of the NR3C1 gene before treatment based on the study of skin biopsies taking into account the response to standard therapy. PATIENTS AND METHODS: Materials and methods: In 57 patients with dyshidrotic lesions, a pathomorphological and immunohistochemical examination of biopsy specimens from a lesion focus of the skin were carried out and a genetic examination was carried out to determine the polymorphic variant C646G of the NR3C1 gene. RESULTS: Results: The results of this study in patients with DEPS showed that in patients with genotype 646 CC, which are torpid to treatment, there is a complex of immune defense with the activation of complement system with activation of C3 and C4d. The activity of expression of CD4 + cells indicating the intensity of the inflammatory response compared with patients with the 646 CC genotype, which were sensitive to treatment. In cases of 646 CG genotypes which were sensitive to topical treatment with steroid, there was a slight decrease in C3 and a decrease in C4d. There was no change in the activation of CD4 + lymphocytes compared with insensitive patients with genotype 646 CG. Moreover, in determining the prognosis and choosing treatment tactics, of great practical value is the presence of immunological parameters that were revealed by the immunohistochemical examinations and were determined by the genotypic peculiarities in patients with DEPS. CONCLUSION: Conclusions: Integral evaluation of the pathomorphological study of biopsy dyshidrotic lesions of sensitive and insensitive patients with different genotypic variants of the C646G of the NR3C1 gene before treatment allows obtaining objective information on the direct effect of glucocorticosteroid therapy. According to the results of our study, the association between NR3C1 gene variants, the pathomorphological features and degree of healing of dyshidrotic lesions of palms and soles was established: the polymorphic version of 646 CC in insensitive patients was associated with additional complement activation of the complement of fractions of C3 and C4d in comparison with sensitive patients of this genotype; рolymorphic variants of 646 CG in sensitive patients - with a slight decrease in the deposition of complement fractions of C3 and C4d іn comparison with insensitive patients of the corresponding genotype.

The gene for a rare autosomal dominant form of pompholyx maps to chromosome 18q22.1-18q22.3.

Pompholyx is a rather common disorder characterized by recurrent crops of vesicles or bullae on the lateral aspects of the fingers, as well as the palms and soles with non-erythematous skin. Until now, very few large families have been reported, so no gene or locus has been identified. Here, we performed a genome-wide search in a large Chinese family to map the chromosome location of the responsible gene. We identified a locus at chromosome 18q22.1-18q22.3 with a maximum two-point LOD score of 3.61 at marker D18S1131 (theta = 0.00). Haplotype analyses indicated that the disease gene is located within 12.07 cM region between markers D18S465 and D18S1362, which corresponds to 8.0 Mb. This is the first locus identified for pompholyx. It will aid future identification of the responsible gene, which will be useful for the understanding of the molecular mechanism of pompholyx.