Background/Objectives: Psoriasis is a chronic, inflammatory, immuno-mediated cutaneous disease characterized by a prominent TNFα-IL23/IL17 immune axis. In recent years, targeted therapies have become standard practice for managing moderate-to-severe psoriasis and have demonstrated efficacy. At the same time, identifying factors associated with the success or failure of TNFα inhibitor therapy remains one of the most difficult aspects in psoriasis treatment. Methods: A clinical, non-randomized study was conducted to evaluate the impact of TNFα inhibitors on the plasma cytokine profiles in patients with moderate-to-severe psoriasis vulgaris (ICD-10 code L40.0). The patients were treated with either etanercept, adalimumab, or infliximab for 16 weeks. Plasma cytokine profiles were assessed using a BioPlex200 System. Results: By the 16th week of therapy, a positive treatment response (PASI ≥ 75) was observed in 51 patients (63%), while 30 patients (37%) showed no response (PASI ≤ 50). When using etanercept, a positive effect was observed in 11 patients (41%), in 14 patients (52%) using adalimumab, and in 26 patients (96%) using infliximab. Analysis of the baseline cytokine levels revealed no differences between the “positive effect” and “no effect” groups, except for IL20, which was 2.61 times higher in the “positive effect” group compared to the “no effect” group, suggesting its potential predictive role in the effectiveness of therapy with TNFα inhibitors. Treatment led to a decrease in IL17F, IL31, sCD40L, and VEGF for all patients, and in IL20 for the “positive effect” group. The increase in ICAM1 in the “no effect” group suggests the possible retention of active migration and the fixation of T cells in the affected skin in these patients. No significant difference in cytokine levels was observed when categorizing patients into subgroups based on the effectiveness of therapy with etanercept, infliximab, and adalimumab; only a pre- and post-treatment difference in the whole cohort was noted. A random forest model showed the importance of VEGF, sCD40L, and ICAM1. Conclusions: The baseline levels of VEGF, sCD40L, and ICAM1, as well as IL20, could serve as potential predictors of treatment effectiveness using TNFa inhibitors. However, this hypothesis requires confirmation with a larger patient population.

The choice of tactics for managing a patient with mycosis fungoides is determined by the stage of the disease. In the early stages of mycosis fungoides, a treatment approach using external therapy and various ultraviolet irradiation spectra (UVB-311 nm and PUVA therapy) is preferable. With insufficient efficiency and / or short remissions in some patients, it is possible to use combined methods in the early stages: PUVA therapy or UVB-311 nm therapy. in combination with systemic therapy, including interferon (IFN) 2b preparations, methotrexate and retinoids. The results of original studies demonstrate an increase in the overall response rate when combining PUVA therapy with IFN- or retinoids in patients with stages IB-IIB. The effectiveness of combined treatment regimens using UVB-311 nm remains insufficiently studied.

Introduction. Dysregulation of the immune system and inflammationis associated with the pathogenesis of psoriasis andmanifestedas significant changes in cytokine profile. This fact can be used to monitor the course of the disease and its treatment. However, the results of these studies are insufficient, sometimes contradictory and require a more in-depth analysis. Aim to identify matches between cytokine profile, clinical scoresof psoriasis severity and the presence of psoriatic arthritis (PsA). Methods. Standardized clinical scores (PASI, BSA, and sPGA) were used to assess the severity of psoriasis. It was defined as moderate if 10 PASI 20 and sPGA was 23, and as severe if PASI 20 and sPGA was 45. Determination of the cytokine levelsin plasma was carried out by the multiplex immunological analysis using xMAP technology. Statistical analysis and visualization of the obtained data was carried out using RStudio for MacOS and the R programming language. Results. The total 113 patients with psoriasis vulgaris of moderate and severe severity were enrolled in the present study. On the basis of PASI score, moderate psoriasis was diagnosed in 55 (48.7%) patients and severe in 58 (51.3%) patients. PsA was diagnosed in 41 (36.3%) patients. Depends on disease severity the differences in the levels of IL-12, IL-20 and IL-22 were revealed. Significant difference in IL-6 level between patients with PsA and without it were shown. We have identified two independent cytokine networks, represented by a cluster of cytokines associated with psoriasis severity scores (IL1TNFIL-17A, IL-22, and IL-20), and a cluster which was not associated with severity (IL-21, IL-23, IL-25, IL-17F, IL-31, IL-33, IL-4, and IL-10). Conclusion. The results of the study for the first time describe the cytokine networks associated with the systemic inflammation in psoriasis; characterize the main effector cytokines determined the severity of the inflammatory response in skin and the development of PsA.

Introduction. The role of the cytokine environment and immune deregulation in the pathogenesis of mycosis fungoides is unquestionable. Despite the fact that one of the methods of therapy for the early stages of mycosis fungoides is phototherapy (PUVA, UVB-311 nm), the effect of ultraviolet radiation on the lymphoproliferative substrate and pathogenetic links in mycosis fungoides has not been fully studied. Aim: to evaluate the effect of NB-UVB and PUVA therapy on the dynamics of cytokine mRNA expression in the affected skin of patients with mycosis fungoides. Material and Methods. A comparative non-randomized study of the cytokine mRNA expression dynamics in the affected skin and of the effectiveness of phototherapy was carried out in 28 patients with early stage of mycosis fungoides. The IL4, IL17A, IL17F, and IL22 mRNA expression was determined relative to the endogenous control GAPDH using the real-time reverse transcription PCR (RT-PCR). Evaluation of the effectiveness of NB-UVB and PUVA therapy was carried out using a BSA score (skin lesion area) and a modified severity-weighted assessment tool (mSWAT) score. Results. The study included 28 patients with early stages (IA–IIA) of mycosis fungoides; 9 patients received NB-UVB and 19 received PUVA therapy. 3.71-fold decrease in mSWAT (p < 0.008), and 3-fold decrease in BSA scores (p < 0.013) were observed in the NB-UVB-treated group. In the PUVA-treated group 3.47- and 2.19-fold lower scores of mSWAT (p < 0.001) and BSA (p < 0.001) were found. There were no significant differences in the expression of the studied cytokines in the NB-UVB-treated group; however, a significant 19 and 72 % increase in IL17F (p = 0.003) and IL22 (p = 0.021) was revealed afterPUVA therapy. Correlation analysis has shown a weak correlation between IL4 and IL17A (r = 0.43, p < 0.027), and IL17F (r = 0.43, p < 0.028) before the treatment. Under the influence of phototherapy, the formation of a cytokine network in the affected skin was observed: there were positive associations between IL4 and IL17A (r = 0.73, p < 0.001), IL17F (r = 0.7, p < 0.001) and IL22 (r = 0.43, p < 0.024); IL17A and IL17F (r = 0.78, p < 0.001); IL22 and IL17A (r = 0.63, p < 0.001) and IL17F (r = 0.66, p < 0.001). In the PUVA-treated group a high negative correlation between IL17A and mSWAT (r = -0.79415, p =0.010586), BSA (r = -0.75432, p = 0.018849) were found. Conclusion: The positive correlations between IL4, IL17A, IL17F and IL22 in the affected skin of patients with mycosis fungoides may underlie the positive effect of phototherapy.

Mycosis fungoides is an epidermotropic primary cutaneous T-cell lymphoma, represented com-posed of small and medium-sized lymphocytes with cerebriform nuclei. Differential diagnosis of cutaneous T-cell lymphoma and chronic autoimmune dermatoses, including psoriasis, may present significant chal-lenges in some cases. We analyzed three clinical cases of mycosis fungoides, in which psoriasis was initially diagnosed. Histological and immunohistochemical studies with a wide panel of antibodies (CD4 CD8, CD2, CD5, CD7, CD3) were performed, and monoclonal T-lymphocyte populations were determined with PCR. We propose an algorithm for diagnosing mycosis fungoides. Keywords: mycosis fungoides, psoriasis, morphology, immunohistochemistrycal study, diagnosis

BACKGROUND:Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma. The aim of the present study was to produce up-to-date information on different phototherapy approaches on skin cytokines in patients with MF.METHODS:A total of 27 patients with mycosis fungoides were treated with phototherapy: NB-UVB (narrow-band ultraviolet B therapy) (10 patients) and PUVA (long-wavelength ultraviolet radiation of spectrum A with the use of skin-photosensitizing furocoumarins) therapy (17 patients). Evaluation of the effectiveness of treatment was carried out using BSA (body surface area) and the modified assessment of the severity of the skin lesions scale (mSWAT) used to quantify tumor mass in cutaneous T-cell lymphomas. Average numbers of procedures were 30.2 and 27.8 in the NB-UVB and PUVA groups, respectively. The median total dose of NB-UVB irradiation was 19.9 J/cm2 and PUVA therapy was 104.0 J/cm2. The overall response to therapy including complete and partial remission was 74.9% in the total group; 70% in the NB-UVB group, and 77.7% in the PUVA therapy group. In the obtained biopsies from lesions, surrounding tissue before treatment and skin samples of four healthy volunteers, the concentration of the IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, sCD40L, and TNF-α cytokines was studied. An increase in IL-4 and TNF-α levels was shown in the lesional skin of patients compared to the skin of healthy controls. After the treatment, positive correlations of mSWAT with the levels of IL22, IL33, and TNF-α in the tumor tissue were found. The levels of IL10 and IFN-γ after PUVA treatment were increased in comparison to baseline. There was no difference in cytokine levels before/after NB-UVB therapy.

Background. In the Russian Federation, there are currently no official statistical data concerning the incidence of cutaneous T-cell lymphomas (CTCL) and the prevalence of CTCL due to the absence of isolation rubrics in the headings of lymphoproliferative diseases of the federal state statistical observation of the separate neologies. Aim. To obtain and analyze the results of the number of patients with CTCL (mycosis fungoides and Szary syndrome) who were on the dispensary observation in medical organizations of dermatovenereological profile in the period 2015 to 2020, the demographic and clinical-epidemiological characteristics, the applied methods of diagnosis and the therapy. Materials and methods. To conduct the study, the questionnaire was developed to obtain the information of the number of patients observed with diagnoses of "mycosis fungoides" and "Szary syndrome" in medical organizations of the dermatovenereological profile of the Federal Subjects of the Russian Federation in the period 2015-2020, were researched the demographic characteristics, the diagnostic methods and the therapy in the studied group of patients. Results. From 24 Federal Subjects of the Russian Federation were obtained the data concerning 163 patients with CTCL under the observation in medical organizations in the period 20152020. From 35 Federal Subjects of the Russian Federation the information showed the absence of patients with CTCL under the observation in medical organizations of dermatovenereological profile. We did not receive the data from 10 Federal Subjects of the Russian Federation. Among 163 patients in 144 (89%) were diagnosed mycosis fungoides, in 17 (10%) Szary syndrome and in 2 (1%) patients were diagnosed other variants of CTCL. The data concerning the demographic characteristics, the diagnosis and the therapy of CTCL were obtained in 155 of 167 patients. We showed that in 44% of cases, the disease was detected by dermatovenerologists, and the diagnosis was most often (39%) determined by oncologists. In 49% of cases the diagnosis was determined only on the basis of the results of histological study, the immunohistochemical study and the polymerase chain reaction were used in 33% and in 3% of cases, respectively. From 155 patients, 52% were under dispensary observation by oncologists, 41% by hematologists, 26% of patients were observed by dermatologists; 99 patients were under dispensary observation by only one specialist: 50 (32%) of patients by oncologist, 40 (26%) of patients by hematologist, 9 (6%) of patients by dermatovenerologist. Nine (6%) of patients were under dispensary observation by three specialists. The information concerning the therapy was available in 92 (59%) of 155 patients. The most commonly applied method of treatment was chemotherapy 72%, phototherapy was received by 26%, the same percentage (18%) was received in two groups: the application of interferon 2b and the application of methotrexate, 1% of patients received radiation therapy. The lethal outcome was registered in 53 (34%) patients. Median duration of the disease from the time of diagnosis to death was 3.55.0 years, the median 2 years, the mode 1 year. Conclusion. For the first time, the attempt was made to summarize the data of the number of patients with CTCL, to describe the demographic, clinical and epidemiological characteristics, the data concerning diagnostics and the therapy. The obtained preliminary results are required further detailing investigation in close cooperation with the professional specialists such as hematologists and oncologists.

The development of both malignant neoplasms mycosis fungoides and cutaneous malignant melanoma is a rare condition; nevertheless, the literature describes both cases of the development of mycosis fungoides in patients with a primary diagnosis of melanoma and the detection of cutaneous malignant melanoma in patients with T-cell lymphomas of the skin. The question of the effect of previous therapy for mycosis fungoides on the risk of cutaneous malignant melanoma remains controversial. Currently, the world community is considering a possible pathogenetic relationship between these two oncopathologies. The clinical observations of the development of cutaneous malignant melanoma in 2 patients with mycosis fungoides presented in the article emphasize the importance of a thorough clinical and dermatoscopic examination of all pigmented formations for the timely detection of malignant melanocytic neoplasms, the presence of which radically affects the further choice of treatment tactics for patients.

Clinical reasoning. There is a need to optimize the use of UV-B-311 nm and PUVA-therapy in patients with mycosis fungoides to determine the duration of the treatment regimen, the number of sessions per week, and ultraviolet irradiation regimen. Goal of research. Evaluation of the effect of the type and duration phototherapy on efficacy in patients with mycosis fungoides. Principle. A comparative, non-randomized study of the effectiveness of phototherapy in patients with mycosis fungoides in the early stages. Evaluation of the effectiveness of UV-B-311 nm and PUVA therapy was performed using the BSA index (area of skin lesions) and Modified Severity-Weighted Assessment Tool (mSWAT), as well as according to the criteria proposed by the International Society for Skin Lymphomas (ISCL), the European Organization for the Study and Cancer Treatment (EORTC) and United States Cutaneous Lymphoma Consortium (USCLC). Results. The study included 14 patients with mycosis fungoides, 5 of whom received treatment with UV-B-311 nm, 9 PUVA therapy. A strong correlation was found between the duration of UV-B-311 nm therapy with mSWAT delta (R = 0.90; p = 0.038) and BSA delta (R = 0.90; p = 0.038), while similar correlation was not found in the PUVA-therapy group (mSWAT (R = 0.24; p = 0.527); BSA (R = 0.09; p = 0.823)). When comparing the effectiveness of therapy between the treatment group UV-B-311 nm and PUVA therapy, delta mSWAT and BSA at the 20th procedure, delta mSWAT and BSA after the end of therapy did not have a statistically significant difference between the UVB-311 nm and PUVA groups. Conclusion. Statistically significant correlation was found between the number of procedures and the effectiveness of therapy In the UV-B-311 nm group. An increase in the number of PUVA therapy procedures (after 20) does not lead to a statistically significant increase in the effectiveness of treatment. Additional research is needed to increase the level of evidence of the results and develop optimal phototherapy regimens.

Обоснование. Существует необходимость оптимизации применения УФВ-311 нм и ПУВА-терапии у больных грибовидным микозом — определение продолжительности курса, количества сеансов в неделю и режима дозирования облучения. Цель исследования. Оценка влияния вида и продолжительности фототерапии на ее эффективность у больных грибовидным микозом. Методы. Сравнительное нерандомизированное исследование эффективности фототерапии у больных грибовидным микозом на ранних стадиях. Оценка эффективности УФВ-311 нм и ПУВА-терапии проводилась с использованием индекса BSA (площадь поражения кожных покровов) и модифицированной шкалы оценки тяжести поражения кожи mSWAT, а также по критериям, предложенным Международным обществом по лимфомам кожи (ISCL), Европейской организации по изучению и лечению рака (EORTC) и Американским консорциумом по кожным лимфомам (USCLC). Результаты. В исследование включены 14 больных грибовидным микозом, 5 из которых получали лечение УФВ-311 нм, 9 — ПУВА-терапию. Выявлена сильная корреляционная связь между продолжительностью терапии УФВ-311 нм с дельтой mSWAT ( R = 0,90; p = 0,038) и дельтой BSA ( R = 0,90; p = 0,038), в то время как в группе ПУВА-терапии подобной связи обнаружено не было (mSWAT ( R = –0,24; p = 0,527); BSA ( R = –0,09; p = 0,823)). При сравнении эффективности терапии между группой лечения УФВ-311 нм и ПУВА-терапии, дельта mSWATи BSA к 20-й процедуре, дельта mSWATи BSA после завершения терапии статистически значимо не различались между группами УФВ-311 нм и ПУВА. Заключение. В группе УФВ-311нм выявлена статистически значимая взаимосвязь между числом процедур и эффективностью терапии. Увеличение числа процедур ПУВА-терапии (после 20) не приводит к статистически значимому увеличению эффективности лечения. Необходимо проведение дополнительных исследований, что позволит повысить уровень доказательности результатов и разработать оптимальные режимы фототерапии.

Aim of the study. To determine the concentration of cytokines in the skin of patients with mycosis fungoides and correlations between their concentration and the value of the modified scale for assessing the severity of skin lesions mSWAT. Methods. The concentration of cytokines was simultaneously determined using xMAP technology: IL-1, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL -31, IL-33, IFN-, sCD40L, TNF- in skin biopsies of 21 patients with early (IAIIA) stages of mycosis fungoides and 4 healthy individuals. Analysis and visualization of the obtained data were carried out using R Statistical Software for MacOS (version 1.3.1056), a free open source software development environment for the R programming language. Results. An increase in the level of IL-4 and TNF- in the lesions in patients with mycosis fungoides compared with healthy individuals was shown (p = 0.025 and p = 0.012, respectively). Correlation analysis revealed the formation of cytokine networks in the skin of patients with mycosis fungoides that were not associated with the value of the modified scale for assessing the severity of skin lesions mSWAT. A tendency towards a negative relationship between the mSWAT and IFN scales was found (p = 0.056). Conclusion. None of the cytokines in lesions and visually unaffected skin from patients with mycosis fungoides were associated with mSWAT values.

Erythroderma is a condition damaging at least 80–90 % of the skin surface, characterized by erythema and peeling. This condition may be a manifestation of various diseases of the skin and internal organs, including malignant lymphoproliferative disorders. Sézary syndrome and the erythrodermic variant of mycosis fungoides are aggressive forms of cutaneous T-cell skin lymphoma, the diagnostics of which is challenging due to the similar clinical pictures of these diseases with benign dermatoses. This article presents two clinical cases of erythroderma in the setting of cutaneous T-cell lymphoma. An analysis of the anamnestic data, the clinical picture and the results of laboratory examinations in patients suffering from this condition allowed the diagnosis of Sézary syndrome to be confirmed. The presented cases reflect the importance of identifying the causes of erythroderma.Conflict of interest: the authors state that there is no potential conflict of interest requiring disclosure in this article.

Currently, phototherapy has been widely used in the treatment of various skin diseases, including mycosis fungoides. The article provides a literature review on the use of various spectra ultraviolet therapy in the treatment of patients with early stages of mycosis fungoides. The mechanisms of action of medium-wave ultraviolet therapy (UVB-311 nm) and PUVA therapy, causing the immunosuppressive, anti-inflammatory and anti-proliferative effect, are described. The results of retrospective studies of PUVA therapy and UVB-311 nm efficacy in patients with cutaneous T-cell lymphoma are presented, as well as modern literature evidence of the need for standardization of phototherapy methods for patients with mycosis fungoides.

Эритродермия — поражение не менее 80–90 % поверхности кожи, характеризующееся эритемой и шелушением, которые могут быть проявлением различных заболеваний кожи и внутренних органов, в том числе злокачественного лимфопролиферативного процесса. Синдром Сезари (СС) и эритродермическая форма грибовидного микоза (Э-ГМ) относятся к агрессивным вариантам течения Т-клеточной лимфомы кожи, диагностика которых сопряжена со многими сложностями ввиду схожести клинической картины этих заболеваний с доброкачественными дерматозами. В статье представлены два клинических случая эритродермии при Т-клеточной лимфоме кожи. В результате анализа анамнестических данных, клинической картины и результатов лабораторного обследования у больных установлен диагноз синдрома Сезари. Представленные случаи подчеркивают важность выявления причин эритродермии. Конфликт интересов: авторы заявляют об отсутствии потенциального конфликта интересов, требующего раскрытия в данной статье.

Mycosis fungoides – the most common form of cutaneous T-cell lymphoma. The pathogenesis of this disease is complex and remains unclear. The article contains a review of the literature devoted to the main mechanisms of T-lymphocytes malignant proliferation, known to date. Data on dysregulation of immune, genetic and epigenetic mechanisms, as well as the role of microenvironment cells in the proliferation of T lymphocytes, are given. Immunophenotypic characteristics and cellular composition of the infiltrate in patients with mycosis fungoides, are described depending on the stage of the disease. Prospective directions in studying molecular-biological predictors of malignant lymphoproliferative diseases development are highlighted.

The aim of the study is to present a successful case in treating primary cutaneous anaplastic large cell lymphoma (PCALCL) occurring with common lesions of the skin and lung tissue. Materials and methods . For the verification of the diagnosis in a patient with three types of skin elements (spot, thin plaque with and without ulceration), differential diagnosis was performed between ulcerative pyoderma gangrenosum, PCALCL, large-cell transformation of mycosis fungoides, and secondary skin lesions under the nodal ALK-negtaive ALCL. A complex of studies, including histological, immunohisto - chemical, cytogenetic studies of skin tumor biopsy, allowed the verification of the PCALCL diagnosis. For the treatment of the patient, intensive induction chemotherapy was used followed by high-dose consolidation and autologous transplantation of hematopoietic stem cells. Results . The selected treatment tactics allowed a long-term complete remission of the disease to be achieved in a patient from the poor prognosis group. Conclusion . An algorithm for the differential diagnosis and tactics of treating is presented for a patient with primary anaplastic large cell lymphoma with a widespread skin lesion and extradermal foci.

The aim of the study is to present a successful case in treating primary cutaneous anaplastic large cell lymphoma (PCALCL) occurring with common lesions of the skin and lung tissue.Materials and methods. For the verification of the diagnosis in a patient with three types of skin elements (spot, thin plaque with and without ulceration), differential diagnosis was performed between ulcerative pyoderma gangrenosum, PCALCL, large-cell transformation of mycosis fungoides, and secondary skin lesions under the nodal ALK-negtaive ALCL. A complex of studies, including histological, immunohisto - chemical, cytogenetic studies of skin tumor biopsy, allowed the verification of the PCALCL diagnosis. For the treatment of the patient, intensive induction chemotherapy was used followed by high-dose consolidation and autologous transplantation of hematopoietic stem cells.Results. The selected treatment tactics allowed a long-term complete remission of the disease to be achieved in a patient from the poor prognosis group.Conclusion. An algorithm for the differential diagnosis and tactics of treating is presented for a patient with primary anaplastic large cell lymphoma with a widespread skin lesion and extradermal foci.

Leprosy (Hansen’s disease) is a chronic granulomatous bacterial disease which mainly affects skin and peripheral nervous system. Leprosy is caused by the obligate intercellular pathogen known as Mycobacterium leprae. Creating experimental models of leprosy is associated with serious problems due to biological characteristics of the pathogen. Numerous attempts to develop experimental models on different types of animals resulted in a few reproducible models on mice and nine-banded armadillos. Strains of knockout mice with genetic defects caused by site-directed mutagenesis are used as a basis for different leprosy models. Experimental models of leprosy are used for screening of anti-leprosy drugs, detection of drug resistance, studies on the pathogenesis of leprosy, production and evaluation of viability of M. leprae, developing of anti-leprosy vaccines.