The dissertation is devoted to the development of a personalized, complex method of treatment of patients with moderate vulgar psoriasis of moderate severity, progressive stage with concomitant alimentary obesity of I-II degree by studying the polarization of macrophages and IL-33 to increase treatment efficiency.
The presence of features of the clinical course of psoriatic disease against the background of grade I-II alimentary obesity and changes in the circadian rhythm was confirmed. It was found that in patients with psoriasis and concomitant alimentary obesity, the evening chronotype of performance prevailed. The influence of circadian rhythm on the severity of psoriasis, quality of life of patients and body weight of patients was studied.
The feasibility of studying the polarization of CD68/CD163 positive macrophages in the biopsy samples of psoriasis-affected skin and indicators of systemic inflammation on the level of IL-33, IL-6 and hs-CRP in the serum of patients with extensive psoriasis vulgaris and concomitant grade I-II alimentary obesity was established for the development of targeted treatment of patients with this comorbidity. The results research show that systemic inflammation is a common link in the pathogenesis of obesity and psoriasis. It is manifested in an increased number of macrophages that produce large amounts of proinflammatory cytokines. Thus, obesity exacerbates systemic inflammation, contributing to a more severe course of psoriasis, which is poorly amenable to standard treatments; it significantly reduces the quality of life of patients and often leads to disability.
It was demonstrated that the increase in IL-33 content in patients with psoriasis and concomitant grade I-II alimentary obesity contributes to a significant increase in the intensity of clinical manifestations of psoriasis, increased levels of IL-6 and hs-CRP and body mass index (BMI).
The role of IL-33 and polarization of M1/M2 macrophages in the pathogenesis and clinical course of psoriasis and obesity was identified and analyzed for the first time. The possibilities of improving the treatment of psoriasis in patients with concomitant grade I-II alimentary obesity by including pioglitazone in the comprehensive therapy of psoriasis were analyzed. For the first time, personalized treatment of patients with psoriasis and concomitant alimentary obesity was developed, which consisted in isolating the phenotype of psoriasis and obesity; using a new biomarker IL-33 to monitor the course and effectiveness of treatment of psoriasis and obesity; using the traditional biomarkers of systemic inflammation IL-6 and hs-CRP; determining the optimal dose of pioglitazone and intake duration in the treatment of psoriasis and obesity.
New data on the effectiveness of pioglitazone in patients with extensive psoriasis vulgaris of moderate severity with concomitant grade I-II alimentary obesity in terms of reduced systemic inflammation, the number of CD68 positive macrophages in biopsy samples of psoriasis-affected skin, the PASI index, DSQL, and reduction of treatment duration were provided. Optimal efficacy was demonstrated with the comprehensive use of pioglitazone at a dose of 45 mg per day for 26 weeks as compared to patients receiving traditional treatment and taking pioglitazone at other doses.
It was found that the use of pioglitazone in the comprehensive treatment of patients with extensive psoriasis vulgaris of moderate severity and concomitant grade I-II alimentary obesity was effective starting from 15 mg, but the highest efficacy was observed when using pioglitazone at a dose of 45 mg once a day for 26 weeks, which led to a decrease in systemic inflammation (IL-33 decreased by 83.7%, IL-6 - by 72%, hs-CRP - by 76.8%), reduction of the PASI index by more than 75 in 100% of patients, stable remission of dermatosis during the year in 80% of patients, reduction of the PASI index by 46.8% and DSQL by 46.9% with recurrence of the disease and reduction of local inflammation, which was manifested by a decrease in CD68+ cells and morphological manifestations of regression of psoriatic plaques, characterized by thickening of the epidermis, orthokeratosis, decreased height of the dermal papillae and the disappearance of branching of the ridges of the epidermis. Thus, the use of the highest dose of pioglitazone in the comprehensive treatment led to the complete normalization of skin morphology.
