Alexey A. Petrov

The aim – to study of the relationship between the prevalence and severity of fibromyalgia (FM) symptoms in patients with psoriatic arthritis (PsA) and the characteristics of the clinical course and type of therapy for PsA Subjects and methods . The study is based on an analysis of data from 97 patients with PsA, who were prescribed adalimumab (25 patients) and netakimab (34 patients) after the initial evaluation. The remaining patients (38 patients) continued taking methotrexate. In addition to a general clinical and laboratory examination, all patients underwent ultrasonography of painful and/or swollen joints, tendons, and ligaments using linear transducers with a frequency of 12–18 MHz, supplemented by power Doppler imaging with a pulse frequency of 6.6 MHz. Results and discussion. In the observed patients with PsA, the diagnosis of FM was established in 24 (24.7%) patients. In patients with concomitant FM, the frequency of active enthesitis was increased (70.8% compared to 28.8% in patients without FM; pConclusion . A relationship has been established between concomitant FM and enthesitis in patients with PsA. The use of an interleukin 17 inhibitor in the treatment of patients with PsA is characterized by a reduction in the frequency and severity of clinical manifestations of concomitant FM.

BACKGROUND: Endothelial dysfunction, a key factor in atherosclerotic vascular damage, increases cardiovascular risk in patients with psoriasis. However, studies on clinically measurable indicators of endothelial dysfunction and their changes during systemic therapy in psoriasis are limited and inconsistent. AIM: Сomparative assessment of the clinical effect of the IL-17 inhibitor Netakimab and Methotrexate on the values of laboratory markers of endothelial dysfunction in patients with psoriasis in comparison with the dynamics of clinical efficacy indicators over 6 months of therapy. MATERIALS AND METHODS: The study observed 66 PsA patients initially prescribed Methotrexate (Group 1: 30 patients) or Netakimab (Group 2: 36 patients). Group 1 received Methotrexate 15 mg weekly with Folic acid, while Group 2 received Netakimab 120 mg subcutaneously at weeks 0, 1, 2, then every 4 weeks. Clinical data were analyzed before, 3 months, and 6 months after treatment. Plasma levels of VEGF, endothelin-1 (En-1), and nitric oxide (NO) were measured before treatment and after 3 months. RESULTS: In psoriasis patients, plasma levels of endothelial dysfunction markers were higher than in the control group: VEGF (19.8 [4.5; 49.4] pg/ml vs. 5.2 [0.5; 9.8] pg/ml, p=0.004), En-1 (286.4 [154; 439] pg/ml vs. 96.5 [32; 188] pg/ml, p=0.002), and NO (4.3 [2.1; 12.5] pg/ml vs. 2.2 [0.2; 5.0] pg/ml, p=0.02). By the third month of therapy, VEGF, En-1, and NO levels decreased, with more significant reductions in Group 2: VEGF decreased by 10.2 [8.4; 13.7] vs. 7.0 [5.6; 11.7] (p=0.043) and En-1 by 184.6 [167; 202] vs. 112.7 [97; 136] (p=0.008) in Group 1. Group 2 also showed a more pronounced decrease in PASI and NAPSI scores at 3 and 6 months. CONCLUSION: The work demonstrated the ability of the IL-17 inhibitor netakimab to reduce initially elevated values of laboratory markers of endothelial dysfunction.

Objective: a comparative evaluation of the effect of the interleukin-17A inhibitor (iIL) netakimab (NTK) and methotrexate (MTX) on laboratory markers of endothelial dysfunction in patients with psoriatic arthritis (PsA) in comparison with the dynamics of clinical efficacy indicators during 6 months of therapy.Material and methods. We performed a dynamic observation of 66 patients with PsA who were prescribed MTX and NTK for the first time. Thirty of them (group 1) received MTX 15 mg/week in the form of subcutaneous (s/c) injections in combination with folic acid 5 mg/week orally; 36 patients (group 2) received NTK as s/c injections at a dose of 120 mg at weeks 0, 1 and 2, and then once every 2 weeks until week 14, from week 14 – once every 4 weeks. The control group consisted of 20 substantially healthy individuals without skin diseases, rheumatic immune-inflammatory diseases of the musculoskeletal system and clinically significant diseases of the cardiovascular system. The clinical data were analyzed before, 3 and 6 months after the start of treatment. In all patients, the concentration of vascular endothelial growth factor (VEGF), endothelin 1 (En-1) and nitric oxide (NO) was analyzed before the start of treatment and at the end of the third month of treatment.Results and discussion. The concentration of laboratory markers for endothelial dysfunction was increased in patients with PsA compared to the control group: the median value of VEGF was 19.8 [4.5; 49.4] and 5.2 [0.5; 9.8] pg/ml (p=0.004), En-1 – 286.4 [154; 439] and 96.5 [32; 188] pg/ml (p=0.002), NO – 4.3 [2.1; 12.5] and 2.2 [0.2; 5.0] pg/ml (p=0.02), respectively. By the end of the 3rd month of therapy, a decrease in the concentration of indicators of endothelial dysfunction was observed. The dynamics of VEGF and En-1 concentrations was more pronounced in patients receiving NTK during the first 3 months of treatment than in patients receiving MTX treatment. The median decrease in VEGF concentration was 10.2 [8.4; 13.7] and 7.0 [5.6; 11.7] pg/ml (p=0.043), in En-1 – 184.6 [167; 202] and 112.7 [97; 136] pg/ml (p=0.008), respectively. A more significant decrease in LEI, PASI and NAPSI was achieved when NTK was used for 3 and 6 months compared to MTX therapy.Conclusion. The work demonstrated the ability of NTK, iIL17A, to reduce the initially elevated levels of laboratory markers of endothelial dysfunction.

BACKGROUND: Pathological angiogenesis is one of the important pathogenetic links of psoriasis. At the same time, the prognostic significance of instrumental methods for studying the severity of angiogenesis in psoriatic plaques remains poorly understood. AIM: Clinical assessment of the correlation between the dynamics of angiogenesis parameters (morphometric parameters of vascular glomeruli and Doppler blood flow in the skin and nail bed) and indicators of the methotrexate clinical efficacy during 12 months of therapy. MATERIALS AND METHODS: The work is based on the clinical data analysis of 82 patients with moderate and severe psoriasis vulgaris in the acute stage, who were prescribed methotrexate after initial examination. Patients underwent Doppler ultrasound examination of the skin in psoriatic plaques area and digital dermatoscopy to study the characteristics of vascular angiogenesis loci before treatment and at 1, 3 and 12 months of methotrexate therapy. RESULTS: As a result of comparative correlation analysis of dermatoscopy and ultrasonographic Dopplerography indicators dynamics and psoriasis clinical index values during the treatment of patients with methotrexate, moderate and strong correlations were established between the values of the average diameter of the vascular glomerulus and the degree of increased blood flow in psoriatic plaque area after 1 month of methotrexate treatment and the values of PASI at 3, 6 and 12 months from the start of treatment (r=0.540.76, p=0.0020.005), as well as between the mean vascular glomerulus diameter values and the degree of skin blood flow increase after 3 months and PASI and BSI indices after 6 and 12 months (r=0.360.74, p=0.0010.036). Disappearance of Doppler signals in psoriatic plaques skin and decrease in vascular glomeruli average diameter after 1 month from the start of therapy in 1.76 [1.38; 2.30] and 1.30 [1.38; 2.30] times increase the probability of achieving clinical improvement after three months of methotrexate treatment. The correlation coefficient between the degree of NAPSI reduction after 6 and 12 months of treatment and the dynamics of Doppler blood flow in the nail bed and resistance index of arterial vessels in the nail bed after three months from the start of treatment varied from 0.53 to 0.73. CONCLUSIONS: The dynamics of instrumental methods indicators for studying pathological angiogenesis correlates with the probability of achieving clinical improvement in psoriasis symptoms during systemic methotrexate therapy.

Background. Evaluation of the severity of pathological angiogenesis in patients with psoriasis can be considered as a promising direction for monitoring the activity of the disease and the effectiveness of systemic therapy. Aims. Evaluation of interconnections between indicators of angiogenesis in the skin and nail bed of psoriasis patients with clinical characteristics of disease course and therapeutic response to the use of methotrexate by a comprehensive study of the morphometric data dynamics of videodermatoscopy in vascular bed of the skin, the severity of blood flow in the dermis and nail bed during ultrasonic power dopplerography and plasma concentrations of vascular endothelial growth factor (VEGF) and endothelin-1 (En-1). Materials and methods. Work is based on the data analysis from a survey of 82 patients with moderate to severe psoriasis vulgaris in the acute stage, who were first prescribed methotrexate in the form of subcutaneous injections at a dose of 1015 mg per week in combination with folic acid 5 mg per week. Before treatment and three months after the start of methotrexate therapy, all patients underwent videodermatoscopy with dimension of the density and size of dilated skin capillaries, ultrasonography of psoriatic plaques and nail bed of affected nails and measurement of doppler blood flow parameters and concentration of VEGF and En-1 in blood plasma. Results. A direct correlation was established between the average diameter of dilated skin capillaries (vascular glomeruli), the degree of increased blood flow in the doppler energy study of psoriatic plaques skin area and the plasma concentration of VEGF and En-1 and values of PASI, BSA, sPGA and DLQI indices, as well as the severity of doppler blood flow of the nail bed and NAPSI index (r = 0.210.73). Under the influence of methotrexate treatment, a decrease in diameter and density of vascular glomeruli (16.2 [12.9; 22.5] versus 25.2 [17.1; 33.7] m before treatment (p = 0.002) and (44.6 [31.6; 53.3] versus 53.5 [34.6; 67.4] before treatment (p = 0.04), respectively), the degree of blood flow in area of psoriatic plaques and the concentration of VEGF and En-1 (12.5 [6.7; 26.8] pg/ml versus 19.5 [4.7; 48.1] pg/ml after treatment (p = 0.002) and En-1 (168.2 [97; 319] versus 274.5 [146; 439] pg/ml(p = 0.003), respectively) was observed. Conclusions. Studied indicators of angiogenesis can be used as additional criteria for assessing the degree of activity and achieving clinical improvement/remission during systemic therapy in patients with moderate and severe psoriasis.

BACKGROUND: Currently, many researchers attach great importance in psoriasis pathogenesis to hyperproduction of vascular endothelial growth factor (VEGF) and endothelin-1, which leads to increased angiogenesis in dermis and mediates processes of immune inflammation. At the same time, possibility of using these angiogenesis biomarkers as additional indicators of immune inflammation activity and disease activity has been poorly studied. AIMS: the purpose of the study was to assess the relationship between serum concentrations of VEGF and endothelin-1, structural changes in the capillary bed according to videodermatoscopy, and severity and prevalence of skin lesions in patients with psoriasis, duration of disease, presence of nail lesions, synovitis, enthesitis and spondylitis, as well as concomitant diseases of the cardiovascular system. MATERIALS AND METHODS: The work is based on examination data analysis of 132 patients with moderate and severe psoriasis vulgaris for the period 20202022. Patients were determined the levels of VEGF and endothelin-1 in blood plasma and underwent digital dermatoscopy to study the characteristics of angiogenesis vascular loci (vascular glomeruli) in the papillary dermis. All psoriasis patients with symptoms of musculoskeletal system lesions were examined by a rheumatologist, which was supplemented by ultrasonography of the joints. RESULTS: According to the results of enzyme immunoassay, it was found that the examined patients had an increased concentration of VEGF and endothelin-1 in blood plasma compared to the control group (respectively 19.5 [4.7; 48.1] pg/ml and 274.5 [146; 439] pg/ml versus 5.2 [0.5; 9.8] pg/ml and 96.5 [32; 188] pg/ml, p=0.004 and p=0.002). It was found that an increase in plasma concentrations of VEGF and endothelin-1 correlates with an increase in density of vascular glomeruli (respectively r=0.65 and r=0.74) and the average diameter of the glomerulus (respectively r=0.58 and r=0.56). A more pronounced increase in plasma concentrations of VEGF and endothelin-1 in patients with psoriasis was noted in patients with psoriatic arthritis and in the presence of synovitis. VEGF levels were higher in patients with severe psoriasis and in patients with nail lesions. Correlation analysis showed the strongest relationship between VEGF concentration and DAS28, DLQI, PASI and NAPSI values, as well as endothelin-1 concentration and PASI, BSA and DLQI values. CONCLUSIONS: The work showed that the plasma concentration of VEGF and endothelin-1 characterizes the degree of angiogenesis expression in the psoriasis pathogenesis, reflects morphology changes in capillaries of the affected skin, and can also be used as a marker of severe psoriasis and an increased risk of developing damage to the nails and synovial membranes of the joints.

In recent years, the sunlight vitamin has become extremely popular and almost mandatory to use, especially because of its pleiotropic effects, although until recently its use was limited to the prevention of the development of pathology of the bone system, in particular rickets in children. Being actually a fat-soluble prohormone of a steroid nature, Vitamin D participates in the endocrine, paracrine and autocrine regulation of the body. The pharmacotherapeutic renaissance of calciferol is associated with the discovery of Vitamin D receptors in most cells of the body, and the presence of enzymes synthesizing the active form of Vitamin D extrarenally, in particular, in the skin, has led to renewed interest and broad discussion in the dermatological community. Is the role of non-bone effects of calciferol, mainly its role in the pathogenesis of autoimmune skin diseases, really justified from the point of view of evidence-based medicine, and is the tendency to consume Vitamin D safe? This article presents the most up-to-date information about the role of Vitamin D deficiency in the mechanisms of immune response development, in some dermatoses. In addition to generalizing the bone and extra-bone functions of Vitamin D to the macroorganism, the mechanisms of formation of some of the most common dermatoses, such as psoriasis, atopic dermatitis and vitiligo are discussed in detail. The review details the biological effects of Vitamin D in the skin. The article analyzes the legality of the use of Vitamin D-based drugs and their effectiveness in dermatological practice.

Objective. Assessment of clinical manifestations and ultrasonographic signs of enthesitis (En) in patients with psoriasis (PsO) and psoriatic arthritis (PsA).Subjects and methods. The study is based on the analysis of survey data from 106 patients with PsO for the period 2018–2021, which were firstly sent by dermatologists for a consultation with a rheumatologist due to musculoskeletal pain. The duration of the period of musculoskeletal pain in the observed patients did not exceed 12 months. In addition to general clinical and laboratory examination, all patients underwent ultrasonography of painful and/or swollen joints, tendons and ligaments using a linear sensor (frequency – 12–18 MHz) of MyLab 50 (Esaote, Italy) apparatus and supplemented by Doppler energy study with a pulse frequency of 6.6 MHz. The OMERACT definitions were used to identify En, synovitis and tenosynovitis.Results and discussion. The diagnosis of PsA was established in 73.6%, osteoarthritis – in 13.2%, gout – in 8.4%, fibromyalgia – in 17.9%. Ultrasonographic signs of En were found in 67.9% of patients: signs of an active inflammatory process in enthesises (decreased echogenicity, thickening and appearance of Doppler signals) were observed in 48.7%, signs of structural damage to enthesial zones (calcifications, enthesophytes and bone erosions) in 25,6% of patients. Isolated En was found in 24.4% of patients, a combination of En and synovitis – in 32.1% of patients, a combination of En and tenosynovitis – in 20.5% of patients. The correlation between the inflammatory domain values of the ultrasoundographic enthesial index MASEI (Madrid Sonographic Enthesitis Index) and the clinical enthesial index LEI (Leeds Enthesitis Index) was 0.71 [0.58; 0.77]. There were less pronounced clinical indicators of enthesial inflammation (lower LEI index values), functional disorders of the joints (lower values of the HAQ-DI index) and laboratory signs of systemic inflammation (lower CRP values) in patients with isolated En in comparison with combination of En and synovitis. Ultrasonographic signs of structural damage of enthesises were observed in 15.4% of patients without clinical and ultrasonographic signs of active En, which may indicate the possibility of a subclinical course of enthesial inflammation in patients with PsO.Conclusion. It was demonstrated that ultrasonography has diagnostic capabilities to identify the site of the inflammatory process in patients with PsA and differentiate patients with isolated En and a combination of En and synovitis in order to select a method of differentiated anti-inflammatory therapy.

The literature review presents data on the role of pathological angiogenesis in the development of psoriasis. Several recent studies have shown, in addition to cytokine imbalance and activation of the T-cell link of immunity, an important pathogenetic link is pathological vascularization. Vascular changes in the dermis appear before clinically visible skin manifestations and can persist for a long time after treatment, as well as the phenomena of neoangigenesis in the synovial membrane and enthesises contribute to the chronicization of inflammatory process in psoriatic arthritis. The article presents an overview of the modern literature on the main regulator of angiogenesis – vascular endothelial growth factor, its role in the pathogenesis of psoriasis and possible therapeutic prospects.

Objective: to assess the relationship between hematological manifestations of systemic lupus erythematosus (SLE) in the early stage of the disease and development of other syndromes and symptoms of the disease, as well as the nature and severity of internal organs damage during the subsequent five-year period.Subjects and methods. The analysis of data of examination of 89 patients with SLE during the five-year period was carried out. The frequency of clinical manifestations of SLE, the level of antinuclear and antiphospholipid antibodies, SLICC/ACR damage index (SDI) depending on the presence of hematological manifestations of SLE in the onset of the disease including leukopenia (LP), thrombocytopenia (TP) and autoimmune hemolytic anemia (AGA) were studied.Results and discussion. In the onset of SLE LP was observed in 21.3%, TP – in 26.9%, AGA – in 8.9% of patients. The presence of LP was associated with an increase of antibodies to SSA frequency, and TP – with more frequent detection of antibodies to Ro-52, cardiolipin and β-2-glycoprotein (pConclusion. Presence of TP in the onset of SLE is a predictor of kidneys, central nervous system, peripheral vessels and heart valves damage during the next 5 years.