The article presents an analysis of literature data on the use of a new group of targeted synthetic disease-modifying antirheumatic drugs (DMARDs) Janus kinase (JAK) inhibitors – tofacitinib (TOFA) and upadacitinib (UPA) – in psoriatic arthritis (PsA). The results of randomized placebocontrolled clinical trials and long-term observational studies indicate the high efficacy and safety of using TOFA and UPA in the treatment of patients with PsA who are resistant to synthetic DMARDs and tumor necrosis factor-α inhibitors. The information obtained so far allows us to recommend JAK inhibitors as a new pathogenetic approach to the treatment of PsA.

According to epidemiological and clinical studies, every fourth patient with psoriasis develops psoriatic arthritis (PsA), and in many cases there is a destructive form of arthritis that leads to disability. Late diagnosis of PsA is associated with a significant reduction in the effectiveness of therapy. Therefore, early diagnosis of this disease is so important.
Objective: to determine the methods for early detection of PsA, in particular the identification of risk factors (RFs) for its development, which will prevent the progression of the disease and the disability of patients.
Materials and methods. The literature review and meta-analysis is presented in two parts. Part 1 of the systematic review included articles on exogenous RFs for the development of PsA published over the past 10 years.
PubMed (MEDLINE), EMBASE, and Google Scholar databases were searched for articles published before March 1, 2021. We searched for currently registered trials in the registers of clinical trials of US (ClinicalTrials.gov), of China (Chinese Clinical Trial Registry) and the WHO International
Clinical Trial Registry Platform. The statistical analysis was prepared in accordance with the international guidelines for systematic reviews and meta-analysis (PRISMA) using the Statistic SPSS 26.0 program (USA).
Results and discussion. 957 articles published up to March 1, 2021 were identified. After further analysis, irrelevant articles were excluded. A total of 73 articles were included in the review and analysis, 32 of which were included in Part 1. The most common exogenous RFs are: mechanical injuries, medications, and psychotraumatic situations.
Conclusion. PsA is a multifactorial disease. Currently, a large number of exogenous RFs for the development of this disease have been established. Knowledge of RFs and the ability to recognize them will help dermatovenereologists and rheumatologists to effectively assess and predict the patient's condition. Correction of modifiable RFs, early prescription of appropriate therapy will help to reduce the number of PsA cases, the development of functional disorders and prevent the growth of disability. However, studies on the comprehensive assessment of RFs in PsA are still insufficient. Further study of methods for the early diagnosis of PsA is needed in order to optimize its treatment.

Objective: to assess the economic burden of ankylosing spondylitis (AS) and non-radiological axial spondyloarthritis (nr-axSpA) in the Russian Federation, as well as the availability and economic prospects for more complete provision of biological disease-modifying antirheumatic drugs (bDMARDs) to patients with AS and nr-axSpA.
Patients and methods. The prevalence of AS and nr-axSpA and organizational aspects of providing with bDMARDs to this category of patients were analyzed.
A variant model has been developed in Microsoft Excel, allows to calculate the indicators of the economic burden of AS and nr-axSpA in the Russian Federation, taking into account the economic losses associated with disability, as well as the low availability of bDMARDs. During study preparation, data from real clinical practice and the opinions of experts in the field of AS from various regions of the Russian Federation were studied.
The economic burden was calculated as the sum of direct and indirect costs per patient and the population. Additionally, the specific economic burden per capita was determined.
Results and discussion. According to expert estimates, the prevalence of AS and nr-axSpA today is 105.0 and 33.2 thousand people, respectively.
The current economic burden of the AS for 2019 is estimated at 21.9 billion rubles per population, or 395.5 thousand rubles for 1 patient. The ratio of direct and indirect costs was 1:4, i.e. 4.7 billion rubles – direct costs (84.3 thousand rubles per 1 patient) and 17.2 billion rubles – indirect costs (311.2 thousand rubles per 1 patient). The burden per capita – 149 rubles.
Nr-axSpA's current economic burden in 2019 reached 3.0 billion rubles, or 182.9 thousand rubles for 1 patient. The ratio of direct and indirect costs is estimated as 2:5, or 0.9 billion rubles – direct costs (53.0 thousand rubles per 1 patient) and 2.2 billion rubles – indirect costs (130.0 thousand rubles per 1 patient). The burden per capita – 21 rubles.
Conclusion. The economic burden of AS and nr-axSpA can be reduced by providing patients with bDMARDs in the required amount: 15% of patients with AS and 10% with nr-axSpA. Due to the imperfection of the regulatory framework, patients with nr-axSpA experience serious difficulties in receiving this therapy within the framework of preferential drug coverage and compulsory health insurance. With the provision of bDMARDs for about 15 and 10% of patients with AS and nr-axSpA, respectively, on the horizon of 5 years, a decrease in disability by 75% and temporary disability by 60% is expected. At the same time, the economic burden for 5 years will decrease by about 40% for each nosology.

Objective: to assess the safety of COVID-19 vaccines in patients with immunoinflammatory rheumatic diseases (IRD) in real clinical practice.
Patients and methods. A cross-sectional study of patients with IRD, who were admitted to V.A. Nasonova Research Institute of Rheumatology for inpatient or outpatient treatment. All patients received at least 1 dose of vaccine against COVID-19 (main group). The control group consisted of vaccinated persons without IRD. All participants were interviewed by the researcher by filling out a unified questionnaire, additional information was obtained from medical records.
Results and discussion. The study included 204 patients with IRD (151 of them were vaccinated with Sputnik V, 31 with Sputnik Light, 19 with СoviVac, 3 with EpiVacCorona; 173 patients received the second component of vaccine) and 131 subjects without IRD (101 of them were vaccinated with Sputnik V, 17 – CoviVak, 5 – Sputnik Light, 2 – EpiVacCorona, 6 – Pfizer/BioNTech; 124 patients received the second component of the vaccine). The number of patients with IRD who had both local and systemic reactions after administration of the first component of the vaccine was significantly less than in the control group (19.6 and 38.9%, respectively; p<0.001). Similar differences were noted after the administration of the second component (15.6 and 27.4%, respectively; p=0.013). Adverse events (AEs) such as pain at the injection site without restriction of movement, weakness, fever, arthralgia/myalgia and chills were significantly more common in the control group after the administration of the first component of the vaccine. After complete immunization, AEs were absent in 35.8% of patients with IRD and in 21% of controls (p=0.006). Exacerbations of IRD and new autoimmune phenomena were not registered in any case.
Conclusion. According to preliminary data, vaccination against COVID-19 in patients with IRD appears to be quite safe. Further studies are needed to investigate the safety, immunogenicity, and clinical efficacy of COVID-19 immunization in rheumatic patients.

The prevalence of fibromyalgia (FM) in the general population is 2–8%, and among patients with rheumatic diseases it is 2–3 times higher. The presence of comorbid FM significantly affects the course of rheumatoid arthritis (RA).
Objective: to assess the effect of FM on RA activity indicators, features of pain syndrome, and quality of life (QoL) of patients.
Patients and methods. The study included patients with a confirmed diagnosis of RA. RA activity was assessed by the DAS28 index. FM was diagnosed according to the 2016 ACR criteria using the FM Diagnostic Questionnaire (FSQ). Patients also completed the central sensitization questionnaires – CS (CSI) and PainDETECT (PD). Pain intensity at rest was assessed using a visual analog scale (VAS, 10 cm), QoL was assessed using the FIQR and EQ-5D questionnaires.
Results and discussion. 55 patients with RA were examined. FM was diagnosed in 24 of them (43.6%). RA activity in the presence and absence of FM (FM+ and FM- respectively) was high: the DAS28 index in the FM+ group averaged 4.58 points, and in the FM- group it was 5.14 points (p=0.227). The median pain intensity according to VAS in the FM+ and FM- groups was 6.5 and 4.0 cm, respectively (p=0.017). Symptoms of CS were more common in patients with FM than in patients without FM (p=0.004). The median score on the PD questionnaire in the FM+ and FM- groups reached 17.5 and 11.0 points, respectively (p=0.015). Patients with FM had lower QoL scores both in EQ-5D (p=0.037) and FIQR (p<0.001).
Conclusion. FM is a serious burden for RA patients. The pain syndrome in the presence of FM is of greater intensity and prevalence, accompanied by neuropathic descriptors, which significantly worsens the quality of life in patients with RA.

Objective: assessment of the dynamics of T- and B-lymphocytes subpopulations in rheumatoid arthritis (RA) during therapy with synthetic disease-modifying antirheumatic drugs (sDMARDs) and biological disease-modifying antirheumatic drugs (bDMARDs): inhibitors of tumor necrosis factor α (iTNFα) and an inhibitor of interleukin 6 receptors (iIL6R ).
Patients and methods. The study included 77 patients with RA who met the 2010 ACR/EULAR criteria (mean age 56 [44; 62] years). Group 1 included 30 (27 women and 3 men) patients with early RA who had not previously received therapy. Group 2 included 20 (14 women and 6 men) patients on sDMARD therapy who were prescribed iTNFα for the first time. The 3rd group is represented by retrospective data of 27 (23 women and 4 men) patients who previously used sDMARDs (MT – 85%, leflunomide – LEF – 15%), in whom iIL6R therapy was initiated for the first time. All study participants initially and 6 months later underwent immunophenotyping of T- and B-lymphocytes by flow cytofluorometry according to the standard method.
Results and discussion. In all groups, there were no significant changes in the studied T-lymphocyte profile during 6 months of follow-up. When comparing the immunogram data of patients treated with sDMARDs and iTNFα, no significant differences in subpopulations of B-lymphocytes were found. At baseline, the iIL6R group had higher levels of naive B-lymphocytes and plasmablasts and low concentrations of «switched» B-cells. For all methods of treatment, the number of «switched» B-cells decreased, while plasmablasts and plasma cells increased.
Conclusion. From the data obtained, it follows that the simultaneous decrease in the levels of memory B-cells and their «switched» forms, plasmablasts and plasma cells can be used as a marker for the early administration of drugs that disrupt the differentiation of B-lymphocytes, in particular, iIL6R.

Objective: to search for an association between basal expression of the AMP-activated protein kinase (adenosine monophosphate-activated protein kinase, AMPK) gene in the blood of patients with rheumatoid arthritis (RA) and disease activity, as well as joint destruction before and after 24 months of methotrexate (MT) therapy.
Patients and methods. The study included 40 patients with RA who met the 1987 ACR classification criteria, with a disease duration of not more than 2 years, with a mean age of 47.5±15.5 years. All patients received 15 mg/week of MT. The number of swollen joints (SJC) out of 44, the number of tender joints (TSC) out of 53, the duration of morning stiffness (in minutes) and RA activity were assessed using the DAS28 index. The concentration of CRP and IgM rheumatoid factor (RF), antibodies to cyclic citrullinated peptide (ACCP) were assessed. To evaluate the radiological progression of RA, the Sharp method modified by van der Heijde was used. Gene expression in peripheral blood cells was determined by reverse transcriptase reaction and real-time polymerase chain reaction.
Results and discussion. During MT therapy, there was a decrease in disease activity by DAS28 index, CRP level, duration of morning stiffness, SJC and TJC. After 2 years, there were no statistically significant changes in the number of erosions, while the number of joints with narrowing of the joint space increased by the end of the study (p=0.004). Treatment with MT resulted in a decrease in AMPK expression. At the same time, patients who achieved remission had the highest level of AMPK before therapy, as did seronegative patients compared to seropositive ones. Based on the ROC analysis, the threshold value of AMPK gene expression was determined, which makes it possible to predict a high probability of a positive effect of MT therapy.
Conclusion. AMPK gene expression is associated with disease activity. Its high initial blood level in RA patients is associated with greater efficiency of MT and, possibly, plays a protective role. With an AMPK gene expression index greater than 3.83, the probability of a positive response to MT is high.

The development of type 2 diabetes mellitus (DM) (DM2) in patients with gout can be influenced by both conventional and directly linked to gout risk factors (RFs).
Objective: to identify RFs for the development of DM2 in patients with gout, including those directly associated with gout, based on long-term prospective follow-up data.
Patients and methods. The study included 444 patients with gout older than 18 years (49 women, 395 men) who did not have DM. The followup period ranged from 2 to 8 years. The studied RFs for DM2 were: gender, age, family history of DM2, obesity, alcohol consumption >20 units per week, insufficient physical activity, unbalanced nutrition, history of hyperglycemia, coronary heart disease (CHD), arterial hypertension (AH), chronic heart failure, antihypertensive drugs, diuretics, glucocorticoids (GCs), urate-lowering therapy, serum levels of cholesterol, triglycerides, CRP, uric acid (UA), glucose, creatinine, glomerular filtration rate <60 ml/min/1.73 m2, the presence of tophi, >4 attacks of gout per year, ≥5 affected joints during the disease.
Results and discussion. DM2 developed in 108 (24.3%) patients. These patients were older, had a family history of DM, more often received antihypertensive therapy, diuretics, and glucocorticoids (49.1; 73.1; 27.8 and 47.2%, respectively) than patients who did not develop DM2 (25.6; 50.5; 14.8 and 36.4%, respectively; p<0.05 for all cases). In addition, patients with DM2 were more likely to have subcutaneous tophi (59.3% versus 30.0%; p=0.001), among them there were more individuals (67.6% versus 31.6%; p=0.001) with frequent attacks of arthritis (>4 attacks per year). UA levels >480 and 600 μmol/l were also significantly more frequent (p=0.0002) in patients with DM2 (71.3 and 34.3%, respectively).
According to logistic regression data, factors that increase the risk of developing DM2 were: family history of DM, a history of hyperglycemia, CHD, AH, intake of GCs, antihypertensive drugs, the presence of tophi, >4 exacerbations of gout per year. Febuxostat use and UA <300 μmol/L were associated with a lower risk of DM2.
Conclusion. The occurrence of DM2 in gout is associated not only with well-known risk factors, but also with hyperuricemia and microcrystalline inflammation. Febuxostat therapy is associated with a lower risk of developing DM2.

The efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs) may be determined by the polymorphic nature of the CYP2C8, PTGS1 and PTGS2 genes.
Objective: to analyze the nature of the distribution of CYP2C8*3 (rs10509681), CYP2C8*3 (rs11572080), PTGS1 (rs10306135), PTGS1 (rs12353214) and PTGS2 (rs20417) among residents of the North Caucasus.
Patients and methods. The study involved 676 volunteers from Russian, Balkar, Kabardian and Ossetian ethnic groups. Carriage of polymorphic markers CYP2C8, PTGS1 and PTGS2 was determined using real-time polymerase chain reaction.
Results and discussion. There were no significant differences between the groups in the rs10509681 and rs11572080 variants of the CYP2C8 gene. In all groups, the carriage of a combination of CYP2C8 and CYP2C9 alleles, encoding the phenotype of normal metabolizers, prevailed with a frequency of about 75% or more. The rs10306135 variant of the PTGS1 gene was found in 5.9% of Russians, 1.1% of Balkars, 5.3% of Kabardians, and 10.6% of Ossetians; variant rs12353214 – in 19.1; 9.4; 10.8 and 9.2%, rs20417 polymorphism of the PTGS2 gene in 0.4; 5; 2.8 and 3.1% respectively.
Conclusion. The data obtained can be used to develop a more rational approach to the prescription of NSAIDs, taking into account the genetic characteristics of the local population in ethnic regions.

Systemic lupus erythematosus (SLE) with juvenile onset (jSLE) is a complex autoimmune disease involving many organs and systems. The single nucleotide polymorphism rs7574865 of the STAT4 (signal switch and transcription activator 4) gene is associated with the risk of developing several autoimmune diseases, including SLE in adults.
Objective: to verify the hypothesis of the association of the rs7574865 polymorphism of the STAT4 gene with a predisposition to jSLE. Patients and methods. In the present case-control study, the rs7574865 polymorphism was studied in 50 children with jSLE and 103 healthy control volunteers using real-time polymerase chain reaction.
Results and discussion. The distribution of genotype frequencies among patients had statistically significant differences compared to controls (p=0.005). The frequencies of GG, GT, TT, GT + TT genotypes in patients with jSLE and in the control group were 36.0 and 63.1% (p=0.003); 54.0 and 33.0% (p=0.021); 10.0 and 3.9% (p=0.153); 64.0 and 36.9% respectively (p=0.003). The frequency of the mutant T allele of the studied polymorphism was higher in patients with jSLE compared with controls (37 and 20.4%, respectively; p=0.002). The association of the T allele with clinical, laboratory, and immunological phenotypes of jSLE was studied.
Conclusion. The obtained data indicate the significance of the rs7574865 polymorphism of the STAT4 gene as an important risk factor for susceptibility to jSLE. An analysis of the distribution of allele frequencies between alternative groups of patients with different phenotypic manifestations of jSLE (their presence or absence) showed an association of this polymorphism with arthritis.

The article systematizes information about various dermatological signs of a novel coronavirus infection – COVID-19. Special attention is paid to the phenomenon of COVID-19-associated angiitis. A clinical case of acroischemia associated with COVID-19 is described: on the 34th day after the onset of infection, a patient developed skin cyanosis of the distal parts of the fingers, which resolved spontaneously after a few days. The need for further research on the skin manifestations of COVID-19 and the development of an effective strategy for managing patients, as well as monitoring the condition of convalescents, is emphasized.

Glucocorticoids (GC) currently remain one of the most important components of the treatment of systemic lupus erythematosus (SLE). However, prolonged use of GC inevitably leads to the development of irreversible organ damage. It has been proven that the use of biological diseasemodifying antirheumatic drugs that block key pathogenetic pathways of SLE has an advantage in patients with high disease activity and dependence on the use of medium and high doses of GC.
Three clinical cases are presented in which patients with active SLE were treated with rituximab and belimumab without the use of oral GC.

The article presents a review of current data on the morphological features of lobular panniculitis (PN) associated with systemic lupus erythematosus (SLE) and dermatomyositis (DM). The clinical and morphological characteristics of PN are presented. The prospects for the use of histological and immunohistochemical methods for the differential diagnosis of PN in SLE and DM are discussed. As the analysis of published works has shown, there are no specific immunomorphological markers of PN. Further research is needed to improve the diagnosis of PN.

The article summarizes literature data on the use of radiography and magnetic resonance imaging to monitor axial spondyloarthritis in real clinical practice.

Local methods are widely used in the treatment of osteoarthritis (OA) and play a significant role in the complex therapy of this disease. A special place among them belongs to intra-articular (i/a) administration of drugs. The most widely used for this purpose are glucocorticoids (GC) and hyaluronic acid (HA) drugs. When comparing the effectiveness of these drugs, it was shown that during the 1st month, HA had more favorable results, after 3 months the results did not differ significantly, and after 6 months, the effectiveness of HA was higher. Some authors believe that the optimal result can be obtained with the combined use of HA and GC.
The efficacy and tolerability of HA drugs in patients with OA have been studied in numerous randomized controlled trials (RCTs), and the data obtained in these studies have been summarized in a number of meta-analyses. At the same time, both in RCTs and in meta-analyses, the results of such treatment were assessed differently. However, when summarizing the materials of various meta-analyses within the framework of a systematic review, it was shown that i/a injections of HA are an effective and safe method of local treatment of OA. However, there are no generally accepted recommendations for the use of HA in the treatment of OA, and the question of their administration in each case is decided individually, taking into account the history, clinical picture, OA phenotype, and tolerability of therapy. The Russian Association of Rheumatologists recommends the use of i/a HA injections in knee OA with synovitis and the use of HA injections to reduce pain and improve joint function.

The modern strategy for the treatment of rheumatic diseases (RD) involves the fastest possible achievement of remission or low disease activity. However, even with the use of the most modern technologies and after a pronounced decrease in the inflammatory activity of the disease, it is not always possible to achieve a complete and stable remission. In such a situation, an important goal of treatment is to maximize the quality of life (QoL) of patients. Pain is one of the leading predictors of a decrease in QoL in patients with RD. At the same time, effective pain control can improve not only the course of individual symptoms of the disease, but also life prognosis as a whole. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most popular drugs for the symptomatic treatment of RD. At the same time, the administration of NSAIDs with a favorable safety profile can improve the quality of life of patients. Meloxicam is the first predominantly selective inhibitor of cyclooxygenase (COX) 2, which appeared in the arsenal of practitioners in the late 90s and has a strong evidence base for efficacy and safety.

Chronic systemic inflammation, which is significantly exacerbated by COVID-19 or in conditions of induced physical inactivity, has a great negative effect on the condition of patients with osteoarthritis (OA). Conversely, diseases associated with chronic inflammation (OA, obesity, hypercholesterolemia, bronchial asthma, diabetes mellitus, chronic kidney disease, deficiency of essential micronutrients, etc.) are the background for a more severe course of coronavirus infection. In patients with this comorbid background, infection with SARS-CoV-2 exacerbates chronic systemic inflammation through activation of the NLRP3 inflammasome with the involvement of toll receptors (TLRs). Inflammasome activation is the central mechanism for the formation of the so-called cytokine storm, which leads to pyroptosis of various cell types and the development of multiple organ pathologies characteristic of COVID-19. In addition, induced physical inactivity (immobilization stress) contributes to the development of sarcopenia and increased pain in OA. The chondroprotectors chondroitin sulfate, glucosamine sulfate, undenatured collagen inhibit TLR and inflammasome activation, inhibit muscle mass loss, and may exhibit a direct antiviral effect (inhibit the replication of the SARS-CoV-2 virus).