Dyshidrotic eczema of the palms and soles (DEPS) is a dermatitis of the hands and feet, characterized by blisters of small to large size with a histological picture of spongy vesicles.
The thesis is devoted to solving an important scientific and practical task –increasing the effectiveness of treatment of patients with dyshidrotic eczema of the palms and soles by determining individual sensitivity to therapy based on assessment of clinical and epidemiological features of the disease, molecular genetic parameters and pathohistologicalchanges in the affected skin.
82 patients with chronic form of dyshidrotic eczema of the palms and soles without symptoms of acute inflammation were included for scientific research and analysis. The genotypes СС, СG, GG according to the polymorphic variant C646G of the NR3C1 gene weredetermined in 68 patients, a comprehensive pathomorphological study of the affected skin in – 57 patients, immunohistochemical study – in 45 patients.
After the above-mentioned examinations, 82 patients with chronic form of dyshidrotic eczema were treated according to the international treatment protocol and a topical corticosteroid drug of class IV power – clobetasol propionate 0,05 % ointment for 6 weeks was prescribed with subsequent evaluation of the effectiveness of therapy. According to the results of treatment after 6 weeks, patients were divided into two groups: Group I – 42 patients who were sensitive to topical therapy (clinical recovery or improvement), Group II – 40 patients who were insensitive to topical therapy, that is, did not receive clinical recovery.
The following clinical and epidemiological features of patients with dyshidrotic eczema of the palms and soles, insensitive to topical steroid therapy are established: aggravating family history (the presence of eczema in first-degree relatives in 30,0 % of cases); significant duration of the disease (from 1 year to 10 years) – in 60,0 % of patients, lack of remission during the last year – 80,0 % of patients, severe clinical manifestations at the time of treatment – 67,50 % of patients, uncontrolled long-term use of topical steroids – 92,50 % of patients.
The severity of clinical manifestations of the disease at the time of examination was assessed by the DASI index. In the group of patients sensitive to topical therapy, mild degree of clinical manifestations was 5,67 times more frequent than in the group of insensitive patients: (Group I – 17 (40,48 %) patients, Group II – 3 (7,50 %) patients) (P<0,001); a severe degree – 2,45 times more frequent in the group of insensitive patients (Group I – 11 (26,19 %), Group II – 27 (67,50 %) patients) (P<0,001).
The C646G polymorphism of the NR3C1 gene had a significant impact on the features and severity of clinical manifestations of dyshidrotic lesions in patients. Genotype 646 CC was associated with mild course of disease, genotypes 646 CG and 646 GG – with moderate and severe pathological process.
Comparative objective assessment of the morphofunctional state of the affected skin in both groups of patients does not give a reliable answer about the possible result of the applied therapy. Immunohistochemical study allowed to objectively evaluate changes in quantitative and qualitative indicators of the pathological process in the skin.
The use of monoclonal antibodies CD4 positive, C3 and C4d complement fractions is the most informative and reliable. The analysis of quantitative traits of CD4 positive, the expression of C3 and C4d deposits of complement fractions in the affected skin, shows a connection with the genetic subtype of the patient and the severity of the disease. It was found that the number of CD4 positive and the expression of C3 and C4d complement fractions decreases according to the severity of dermatosis, especially in patients with GG genotype.
During 6 weeks of treatment with topical steroids, 42 (51,20 %) patients of Group I had a positive effect on treatment (clinical recovery and improvement of clinical manifestations) (2=5,042; P=0,025). 40 patients who were insensitive to topical treatment were offered systemic treatment with cyclosporine 50 mg twice a day. 15 patients refused treatment for various reasons, 25 patients with a permanent course of the disease were treated with cyclosporine. Within 12 weeks of treatment, 16 patients experienced clinical recovery and 6 patients experienced clinical improvement. The effect was not examined in 3 (12,0 %) patients.
The duration of remission within a year of observation after taking cyclosporine was (180,69±7,72) days.
A method of personalized pathogenetic treatment of patients with DEPS is proposed, taking into account different genotypic variants of C646G of the NR3C1 gene and features of immunohistochemical changes in the epidermis and dermis.
