ORIGINAL ARTICLES. CLINICAL MEDICINE
Background. Each individual has a unique skin microbiota that includes a diverse resident and transient community displaying an individualized composition. This study focuses on the identification of skin microbial genomes in patients with chronic microbial eczema.
Objective. To evaluate the clinical efficacy of complex therapy in patients with microbial eczema using personalized selection of topical antibacterial agents while taking into account the determination of antibiotic resistance by whole genome sequencing.
Methods. The prospective сomparative randomized study involved 60 patients with microbial eczema in the exacerbation stage, who were randomly divided into two groups of 30 people each: main and control groups. In the control group (group 2, n = 30) patients were treated according to the Federal Clinical Guidelines. In the main group (group 1, n = 30) patients were also treated with conventional therapy, while topical antibacterial agents were selected in a personalized manner based on antibiotic resistance data. On the 21st day of therapy, an emollient with a probiotic component was added to the treatment regimen for patients of both groups. The patients underwent therapy, observation, and examination at the Department of Dermatovenerology of the Kuban State Medical University of the Ministry of Health of the Russian Federation. The clinical study was performed between December 2023 and December 2024. The observation periods in the study were divided into several stages: before the start of therapy, on days 14, 21, and six months after treatment. In this study, the microbiome of the affected skin areas of the patients was analyzed comparatively, and the effect of topical antibacterial preparation selected on the basis of whole genome sequencing data was evaluated. The laboratory stage of the present study was conducted at two sites: CL Lab Clinical Diagnostic Laboratory (“СL Medicalgroup” LLC) in Krasnodar and Serbalab Genetic Laboratory (“Serbalab” LLC) in St. Petersburg. The Eczema Area and Severity Index (EASI) was used to evaluate the skin pathologic process. Statistical processing of data was performed using the Statistica 12.0 software package (StatSoft, USA) and Microsoft Exel 2010 (Microsoft, USA). Quantitative parameters were statistically described using median and quartiles (Me (Q1;Q3)), along with mean with standard deviation (M ± SD). Differences were considered statistically significant at the error level of p < 0.05.
Results. During exacerbation in patients with chronic microbial eczema, the microbial equilibrium shifted towards an increase in microorganisms Staphylococcus aureus, Clostridioides difficile, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli that were present on the affected skin areas, while the number of functional bacteria was limited. A more pronounced tendency to restoration of healthy microbiome in the patients of the main group was observed as soon as the 14th day. By the 6th month of treatment, the patients of the main group experienced a greater decrease in microbial colonization in the foci of microbial eczema lesions than in the control group, whereas the proportion of Bifidobacterium and Lactobacillus functionalis was increased compared to the pre-treatment values by 2.31 and 2.10 times, respectively. In addition, the disease relapse occurred in two patients in the main group (versus five in the control group), which may indicate the higher efficacy of the therapy method proposed in the study.
Conclusion. Whole genome sequencing method identifies the taxonomic diversity of the microbiome. Personalized application of topical antibacterial agent in complex therapy in the main group of patients promotes faster restoration of healthy skin microbiome than in the control group.
Background. Acquired skin hyperpigmentation has a pathogenetic origin in the increased activity of melanocytes and melanin synthesis, as well as its saturation of neighboring keratinocytes. However, the issue of molecular mechanisms of occurrence is not fully disclosed. Maintenance of increased cellular metabolism and synthetic process during melanogenesis requires a large amount of energy and plastic substrates to build cell membranes. Thus, the gas transport function of blood erythrocytes and levels of lipoproteins of different classes in serum in patients with hyperpigmentation seemed relevant to study in order to identify their possible contribution to the pathogenesis of this condition.
Objectives. To identify systemic changes in blood parameters in patients with acquired skin hyperpigmentation before and after treatment as well as to assess their possible contribution to the mechanisms of skin hyperpigmentation formation.
Methods. A cohort prospective study included 50 women aged 42–44 years, living in Rostov-on-Don, who sought medical care at the clinic of the Davinci Group LLC. The study group, 25 patients with a mean age of 41.88 ± 1.45 years, had hyperpigmentation, and the control group of individuals with a mean age of 41.84 ± 1.57 years did not have hyperpigmentation, having come to the clinic for cosmetic purposes. The laboratory stage of the study was conducted in a laboratory of the Department of General and Clinical Biochemistry No. 1 of the Rostov State Medical University of the Ministry of Health of the Russian Federation. Two groups (25 people each) were formed according to the criterion of presence or absence of hyperpigmentation. The target parameters of the study were screening of lipid and cholesterol profiles in blood serum, and assessment of the 2,3-diphosphoglycerate level and products of carbohydrate metabolism in erythrocytes. Total cholesterol, triacylglycerides, and high-density lipoproteins were determined by enzymatic colorimetric method using a Chronolab AG diagnostic kits (Chronolab, Switzerland). The concentration of low-density lipoproteins was determined by turbidimetric method, while the concentration of very low-density lipoproteins was calculated with the “concentration of triacylglycerides / 5” formula. The level of 2,3-diphosphoglycerate was measured by non-enzymatic analysis in trichloroacetic acid filtrate of hemolyzed erythrocytes, while the concentration of lactate and pyruvate was determined using an automated biochemical analyzer VitaLine-200 (Vital Development Corporation, Russia). The collected database was analyzed using descriptive and comparative statistical analysis in Statistica 12.0 software package (StatSoft, USA). Differences were considered statistically significant at p < 0.05.
Results. The study of metabolic features of lipoprotein metabolism of different classes in patients with hyperpigmentation indicated an increase in the levels of certain classes of lipoproteins compared to the control group. A statistically significant increase in the concentration of total cholesterol, triacylglycerides, along with a tendency to a decrease in high-density lipoproteins were observed. The median value of the total cholesterol level in the blood of patients with hyperpigmentation was found to be significantly higher than in the control group by 22.2% relative to the control (p = 0.003), with a statistically significant increase in the median concentration of triacylglycerides relative to the control (p = 0.032). Women with clinical manifestations of skin hyperpigmentation showed a 58.5% decrease in pyruvate concentration compared to the control group (p = 0.029), whereas the lactate level was found to be 193.9% higher than in the control group (p < 0.001). The lactate level in the study group statistically significantly increased after treatment compared to the values before treatment thus approaching the control values (p = 0.609). Meanwhile, the median concentration of 2,3-diphosphoglycerate in the study group before treatment was higher compared to the median in the control group, albeit the difference was not statistically significant (p = 0.139).
Conclusion. Patients with hyperpigmentation were found to have statistically significantly increased levels of certain classes of lipoproteins, such as triacylglycerides, and total cholesterol in the blood. These changes indicate an ongoing need of cells for synthesis of membrane lipids and maintenance of increased cellular metabolism, which is required for increased regeneration of the epidermis. The obtained data reveal a change in the priority of oxygen distribution in cellular structures and tissues, followed by a significant increase in the level of lactate and the development of local tissue hypoxia.
Background. Stevens — Johnson syndrome and toxic epidermal necrolysis are severe diseases featuring lesions of the mucous membranes and skin, with a possible lethal outcome. These diseases are most often triggered by various infections and medications, e.g., nonsteroidal anti-inflammatory drugs, antibacterial drugs, B vitamins, antiepileptic drugs, etc. Early diagnosing is therefore critical for immediate discontinuation of the inducing agent and initiation of treatment.
Objectives. To study etiologic factors, the severity level and mortality rate in hospitalized patients with Stevens — Johnson syndrome and toxic epidermal necrolysis.
Methods. An observational cohort retrospective study was conducted to analyze the case histories of 229 patients with Stevens — Johnson syndrome and toxic epidermal necrolysis hospitalized in the Allergology Department of the Municipal Clinical Hospital No. 21 in Ufa, in 2014–2023. The diagnoses of Stevens — Johnson syndrome and toxic epidermal necrolysis were established by complex investigations. The clinical criteria for Stevens — Johnson syndrome were acute conditions characterized by mucous membrane erosions and skin lesions (atypical michenoid lesions, bullae, and/or erosions) with maximum epidermal detachment of less than 10% of the total body surface area; for toxic epidermal necrolysis, maximum epidermal detachment of more than 30% of the total body surface area in addition to the above symptoms. Cases with maximum epidermal detachment of 10–30% of the total body surface area were classified as overlapping Stevens — Johnson syndrome and toxic epidermal necrolysis. The study group comprised 229 patients, including 44.1% men and 55.9% women, aged 45 (34; 61) years. Patients were divided into three groups: Group 1 (n = 83/229, 36%) had Stevens — Johnson syndrome, Group 2 (n = 41/229; 18%) had a combination of Stevens — Johnson syndrome and toxic epidermal necrolysis, and Group 3 (n = 105/229; 46%) had toxic epidermal necrolysis. The data analyzed in patients in this study included demographic information (age and sex), medical history and comorbid conditions, prior medication use, and the time between the first administration of the causative drug and the onset of symptoms of all disease groups studied. The SCORTEN (Score of Toxic Epidermal Necrosis) scale was used to assess the severity of course and prognosis in patients with toxic epidermal necrolysis. Hospital mortality was also studied in this group of patients. Differences were considered significant if the p-level of rejection of the null hypothesis of their absence did not exceed 0.05.
Results. The leading causes of disease development were medications, with a total of 127/229 (55%), among which antibiotics prevailed with 52/127 (41%), non-steroidal anti-inflammatory drugs with 31/127 (24.4%), anticonvulsants, antiretrovirals, and B vitamins with 6/127 (4.7%) each. The second frequently registered trigger was viral infections, 34/229 (14.8%) including herpes simplex virus types 1 and 2, human immunodeficiency virus, Epstein — Barr, and hepatitis viruses. The etiologic factor could not be established in almost one third of patients, 66/229 (28.8%). Manifestation of symptoms depended on the type of reaction, with toxic epidermal necrolysis developing more often in the first week and Stevens — Johnson syndrome manifesting predominantly in the fourth week. Most patients experienced the diseases for the first time; recurrent manifestations were registered only in 21/229 (9.2%) patients. The clinical presentation included skin lesions 229/229 (100%), hyperthermia 155/229 (67.7%,), oral mucosal erosions 201/229 (87.8%) and genital erosions 142/229 (62%), and conjunctivitis 162/229 (70.7%). Toxic epidermal necrolysis was associated with a more severe course. The calculated mortality for 105 patients with toxic epidermal necrolysis according to the SCORTEN scale was 21.38% (22 cases). The mean SCORTEN score was 2.39 ± 0.59. However, 4 patients died (mortality rate 4%). All patients with lethal outcome were scored 4 on the SCORTEN scale.
Conclusion. Drug exposure and viral infection were more frequent causes of toxic epidermal necrolysis than Stevens — Johnson syndrome and the combination of Stevens-Johnson syndrome and toxic epidermal necrolysis. In toxic epidermal necrolysis, symptoms more frequently developed in the 1st week after drug administration. However, the mortality rate of patients amounted to 4%, which was significantly lower than the estimated (21.38%) according to the SCORTEN scale. This may be due to early diagnosis of the disease and timely provision of medical care in the hospital.
Background. Bullous dermatoses are severe life-threatening antibody-induced organ-specific multifactorial diseases resulting from a genetic predisposition. Systemic glucocorticosteroids are the first-line therapy for many bullous dermatoses. However, there is a small though significant proportion of patients who are resistant to basic therapy with systemic glucocorticosteroids. Although studies of the steroid resistance have been performed at the level of receptors and genes in the serum of patients, no studies of this mechanism have been carried out at the level of blister fluid locally in the area of blister formation.
Objectives. To estimate cytokine (interleukin 10, 15, 4, tumor necrosis factor alpha), chemokine (eosinophil chemotactic protein, interleukin 8) profiles and granulysin levels in patients with bullous dermatoses in serum and blister fluid, as well as their possible relationship with steroid resistance.
Methods. The observational cohort controlled study included 67 patients with bullous dermatoses hospitalized between January 2020 and December 2023 in the V.A. Rakhmanov Clinic of Skin and Venereal Diseases of the University Clinical Hospital No. 2 of the I.M. Sechenov First Moscow State Medical University (Sechenov University) and the Department of Allergology and Immunology of the Municipal Clinical Hospital No. 24 of the Moscow City Health Department. The patients were classified into three groups by diagnosis. The first group included patients with pemphigus vulgaris (n = 43), the second was patients with bullous pemphigoid (n = 11), and the third consisted of patients with Stevens — Johnson syndrome and toxic epidermal necrolysis (n = 13). The control group consisted of 43 healthy donors, whose biological material was obtained from the Blood Center of the I.M. Sechenov First Moscow State Medical University (Sechenov University). After a 3-week course of systemic glucocorticosteroids, the groups of patients with bullous dermatoses were stratified into steroid-resistant and steroid-sensitive subgroups, respectively: with pemphigus vulgaris 18/25 patients; with bullous pemphigoid 3/8; with Stevens — Johnson syndrome and toxic epidermal necrolysis 1/12. Due to the small number of patients, the data of steroid-resistant and steroid-sensitive patients with Stevens — Johnson syndrome and toxic epidermal necrolysis were not statistically analyzed. The main indicators of the study comprised interleukins 10, 15, 4, tumor necrosis factor alpha, eosinophil chemotactic protein, interleukin 8, and granulysin levels in serum and blister fluid of patients depending on the presence or absence of steroid resistance. Statistical processing of data was performed using Statistica 10.01 software package (StatSoft, USA), Microsoft Excel 2010 (Microsoft, USA) and IBM SPSS 24.0 software (IBM, USA). Differences were considered statistically significant at p < 0.05.
Results. The concentrations of tumor necrosis factor-α, interleukin 10, granulysin, as well as chemokines — interleukin 8 and eosinophilic protein — were statistically significantly higher in serum in patients with pemphigus vulgaris, Lever’s bullous pemphigoid, and Stevens — Johnson syndrome and toxic epidermal necrolysis compared to the control group (p < 0.001). Significantly lower levels of tumor necrosis factor-α, particularly in blister fluid as opposed to serum, correlated with steroid resistance in patients with pemphigus vulgaris (p < 0.05). Reduced levels of the key neutrophil chemoattractant may indicate impaired recruitment of immune cells to the lesion, thus being a potential biomarker of the refractory course of the disease. Meanwhile, steroid-resistant patients with bullous pemphigoid had statistically significantly high levels of interleukins 4, 8, 15, and granulysin in their blister fluid compared to steroid-sensitive patients (p < 0.05). Due to this, differences in inflammatory marker profiles associated with insensitivity of patients to hormone therapy are emphasized. Importantly, most patients with bullous pemphigoid responded adequately to therapy (8/11) with systemic glucocorticosteroids compared to the pemphigus vulgaris group. In patients with Stevens — Johnson syndrome and toxic epidermal necrolysis, the level of granulysin (median 12,105 ng/mL) in blister fluid was statistically significantly higher compared with pemphigus vulgaris (median 10,842 ng/mL; p = 0.024) and bullous pemphigoid (median 10,335 ng/mL; p = 0.048). The findings suggest that analysis of this biomarker in blister fluid can be applied to the diagnosis as well as differential diagnosis of bullous dermatoses.
Conclusion. This study identified potential predictors of response to therapy with systemic glucocorticosteroids in the blister fluid of patients with pemphigus vulgaris and bullous pemphigoid. In the long-term, the analysis of blister fluid can be used complementary to the histologic method as an express diagnostic test, differential diagnosis of severe bullous dermatoses, real-time monitoring of response to therapy, and prognosis of the severity of the course of these diseases. Additionally, a timely administration of adjuvant therapy to patients’ refractory to systemic steroids would assist in minimizing the risk of complications and side effects.
Background. Alopecia areata is an autoimmune disease affecting hair follicles that is frequently associated with atopic diseases. Studies on cytokine profiles in the context of atopic comorbidities help to identify the key immune mechanisms and specific immunophenotypes. The present study aims to identify immune differences in alopecia areata depending on the atopic status.
Objective. To assess the serum levels of the main proinflammatory and regulatory cytokines in patients with alopecia areata, taking the presence of atopic diseases and the severity of the process into account.
Methods. An observational cohort cross-sectional study was conducted at the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology of the Moscow City Health Department. The study included 44 alopecia areata patients aged 5–17 years, who were divided into two groups: 1) patients without atopy (n = 17); 2) patients with concomitant atopic diseases (n = 27). The severity of alopecia areata was graded using the Severity of Alopecia Tool (SALT). Cytokine concentration was studied via a multiplex assay (Luminex 200, ProcartaPlex Human Cytokine&Chemokine Panel 1A, 34plex). Of the 34 target parameters, granulocyte-macrophage colony-stimulating factor, interleukin-1β, and interleukin-15 were excluded from analysis due to the lack of detection in ≥20 participants. The remaining 31 parameters were compared between the groups and with the comparable healthy control group (n = 30). The correlation between the serum cytokine levels and alopecia severity was analyzed. The obtained data were statistically processed using Statistica 10.0 (StatSoft, USA) and Microsoft Excel 2016 (Microsoft Corporation, USA). The statistical significance level is α = 0.05. In order to estimate the correlation coefficient (r) and its statistical significance (p), Spearman’s coefficient was used. SCImagoGraphica software (SCImago LAB, Spain) was used for the graphic representation of the obtained results.
Results. Differences between Groups 1–2 and the control group were found for 18 cytokines. Group 2 patients (with atopy) exhibited differences from the control group (p < 0.005) in the distribution of levels of all Type 2 cytokines, Type 1 cytokines (interleukin-2, interleukin-12, and tumor necrosis factor alpha and beta), and T helper 17 cytokines (interleukins 21, 22, 23, and 27), except for interleukin-17A. In Group 1 (without atopy), interleukin-4, interleukin-9, and eotaxin levels did not differ from those in the control group, while the level of interleukin-17A was elevated (p = 0.007). A direct comparison of the distribution of cytokine levels showed no statistically significant differences between Groups 1 and 2 in any of the parameters. The correlation between cytokine levels in alopecia areata patients and the disease severity was analyzed in all patients without dividing them according to their atopic status due to the limited sample size in the subgroups. The levels of interleukins 1 alpha, 10, 21, 22, 23, 27 and tumor necrosis factor beta were positively correlated with alopecia severity, especially interleukin-23 (r = 0.372, p = 0.008); a negative correlation with SALT scores was observed for interleukin-2 (r = −0.457, p = 0.011) and interleukin-4 (r = −0.489, p = 0.006).
Conclusion. The obtained results confirm the complex and systemic nature of immune abnormalities in alopecia areata. T helper 2 cytokines are clearly involved in the pathophysiologic process, with comorbid atopic diseases enhancing the T helper 2 response, potentially modulating interleukin-17A expression. The severe course of alopecia is associated with the activation of T helper 17 mediators (except for interleukin-17A) and a decrease in the levels of interleukins 2 and 4. The obtained data justify the appropriateness of personalized therapy that takes the atopic status and cytokine profile into account.
REVIEW
Background. Socioeconomic determinants have a great influence on the access of preventive health care services.
Objective. The purpose of this systematic review is to assess barriers, facilitators, and policy implications for healthcare equity from the global data.
Methods. A systematic review was carried out across different regions and income classes. Data from studies regarding socioeconomic factors, healthcare system characteristics, and equity metrics were analysed. The statistical methodologies used were regression analyses, concentration indices, and inequality measures to measure the barriers and facilitators.
Results. The results suggested that financial constraints were the primary barrier to equity in low- and middle-income settings, supplemented by geographic inaccessibility and cultural factors. In the high-income settings, there were significant socioeconomic inequities despite the implementation of universal health coverage frameworks. The facilitators were universal health coverage, community-based interventions, and targeted reforms. Prominent trends of pro-rich utilization and gender disparities dominated, while equity-sensitive policies revealed success in closing healthcare gaps. Concentration indices had a significant inequity with moderate CI: 0.062 to high CI: 0.29.
Conclusion. The study shows multifaceted effects of socioeconomic determinants on access to health care, and there is a need for context-specific and equity-sensitive policies. There is a requirement to overcome financial and geographic barriers, improve health literacy, and integrate community-driven approaches in achieving universal healthcare accessibility.
CLINICAL CASE
Background. Pityriasis lichenoides et varioliformis acuta, also known as Mucha-Habermann disease, is a benign form of parapsoriasis characterized by acute onset, widespread polymorphous inflammatory eruptions, and systemic symptoms. Rare disorders such as pityriasis lichenoides et varioliformis acuta present a diagnostic and therapeutic challenge that requires interdisciplinary expertise.
Case description. The article presents a case of pityriasis lichenoides et varioliformis acuta in a boy referred for hospitalization at the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology; the patient had recurrent episodes of bright erythematous, papular, and vesiculo-pustular centripetal eruptions, whose regression resulted in hypopigmentation and varioliform scarring. The performed dermoscopy revealed a pronounced vascular pattern, monomorphic dotted and linear vessels. The pathomorphological study confirmed the diagnosis of pityriasis lichenoides et varioliformis acuta. The typical clinical course of pityriasis lichenoides et varioliformis acuta coincided with an infectious process (enterovirus infection), which is also characterized by vesicular skin eruptions. Treatment recommended by pediatricians had no effect on the regression of skin eruptions. The average time from the appearance of eruptions to the correct diagnosis was about two months.
Conclusion. PLEVA is a rare disorder, primarily developing in children, which makes its diagnosis a complex and time-consuming process. Infectious agents should be considered important disease triggers in children. It is believed that a favorable outcome and prolonged remission are characteristic of patients with the onset of the disease after the age of five years. Therefore, the follow-up of patients with the onset of the disease at the age of four years (on the example of this clinical case) should be carried out with the participation of pediatric specialists and dermatovenereologists throughout the entire cold season, when the risk of viral infections and pityriasis recurrence exists.
HISTORY AND SOCIOLOGY OF MEDICINE
Background. The article analyzes the provision of media support for the healthcare system as an agenda-setting factor in the context of digital transformation. It is established that this area of research fits logically into the framework of health communication studies. In this work, the provision of media support for the healthcare system is considered within the agenda-setting theory. It is shown that in the context of digital transformation, new media, including state public websites, become a source of information forming the image of institutional structures and organizations, as well as a factor affecting the behavioral initiatives and practices of the population.
Objective. To analyze the provision of media support for the healthcare system as an agenda-setting factor in the context of digital transformation.
Methods. The empirical base of the study comprised semi-structured expert interviews with public relations specialists employed in the healthcare system of Sverdlovsk Oblast (2020, n = 12), reports on the publication activity of medical organizations (2022, n = 11,054), publications on the website “Health of the Urals population” (2023, n = 1182), requests from members of the public (2020–2023, n = 54568), and data from the Applied Research Agency (2020–2023, n = 89527).
Results. The findings indicate that the media support provided for the healthcare system is based on materials that confirm the implementation of the national projects “Healthcare” and “Demography,” as well as news about the current activities of the Ministry of Health / medical organizations and the prevention of noncommunicable diseases. Requests from members of the public were primarily related to individual local issues, which can also be newsworthy.
Conclusion. Drawing on the thematic analysis, the article states that the agenda built by the Ministry of Health of the region can be expanded to include the public agenda set by the members of the public, including through their requests. It should include issues related to the maintenance of a healthy lifestyle, as well as publications aimed at improving the health literacy of the population. This approach can potentially not only reduce the number of requests, but also contribute to the development and strengthening of health-promoting behavior practices of different population groups.
ISSN 2541-9544 (Online)