Osteoarthritis (OA) is currently considered as a heterogeneous disease that can be represented by different subtypes. It is the study of OA phenotypes that is one of the strategic areas for the development of researches on this nosological entity, which will further allow a personified approach to patient therapy and ensure the rational use of financial resources of health care.

The paper describes in detail the current researches on this issue. It discusses attempts to identify different OA types according to demographic data (age, race, gender, etc.), comorbidity (including depression), nature of pain (intensity, pathophysiological mechanisms of its development), biochemical markers, genetic and biomechanical predictors, hormonal status in patients, and structural changes detected by ultrasound, magnetic resonance imaging, and computed tomography, etc. 

For the first time, the paper presents in detail the prevalence of osteoarthritis (OA) and considers the predictors of disease development and progression. The clinical classification of OA and its place in the ICD-10 are described. The clinical presentation of the disease is characterized in detail according to the localization of the process. It is noted that there is a change in the understanding of OA as a classic model of nociceptive pain. The paper depicts clinical, laboratory, and instrumental methods for diagnosing the disease, as well as classification and diagnostic criteria; much attention is paid to the current principles of OA therapy according to the Russian clinical recommendations and the guidelines of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the European League Against Rheumatism (EULAR).

The paper reviews the new European League Against Rheumatism (EULAR) guidelines covering a wide range of rheumatology issues discussed at the 2018 EULAR Congress.

Objective: to describe the portrait of a patient with rheumatoid arthritis (RA) in real clinical practice, to assess disease activity from the point of view of a physician and a patient, functional status, quality of life (QOL), and the efficiency of the therapy performed.

Patients and methods. The investigation enrolled 976 RA patients from a cohort of patients in the TERMINAL-I multicenter study, who, when visiting a rheumatologist, independently assessed the disease activity and QOL using a computer system (the «Computer Terminals of SelfAssessment for Patients with Rheumatic Diseases» project). The mean age of the patients was 52.30±13.3 years; women accounted for 85%; the median disease duration 8.0 [4.0; 14.0] years. Baseline clinical parameters and pharmacotherapy were evaluated for 6 months. The disease activity was determined by the DAS28 and RAPID-3 indices; functional status and quality of life were evaluated by the HAQ and the EQ-5D, respectively.

Results. 83% of the RA patients were positive for rheumatoid factor and 60% were for anti-cyclic citrullinated peptide antibodies. There was a preponderance of patients with high (40.5%) and moderate (46.8%) RA activity; 6.9% were observed to have a low activity; 5.8% had clinical remission. The mean values of DAS28 and RAPID-3 were 4.7±1.3 and 13.7±3.6, respectively. Only 14.3% of patients had a good functional status that was comparable with the population-based control (HAQ≤0.5). The remaining patients were found to have a substantial decrease in joint functional parameters (median HAQ 1.88 [1.0; 2.5]) and EQ-5D QOL (0.60 [0.60; 0.74). Prosthetic joints were present in 7.4% of patients. At visit 1 to a rheumatologist, the therapy was changed in 15% of patients. During 6-month follow-up, conventional disease-modifying anti-rheumatic drugs were taken by almost all (91.2%) patients. Of them, 70.9% of the patients were treated with methotrexate (MTX): 77.0% received the latter at a dose of 15 mg/week and 23.0% had it at a dose of >15 mg (17.5 to 40 mg/week). Glucocorticoids could be stopped in 20.5% of the patients within six months. Tumor necrosis factor-α inhibitors and anti-B-cell therapy were used in 6.6 and 16.2% of patients, respectively. At 6-month follow-up (Visit 2), 54% of patients achieved a 20% clinical improvement in the ACR criteria. At the same time, the DAS28 scores decreased substantially from 4.5±1.2 to 3.8±1.1 (p = 0.0001). There was a minimal functional improvement in the HAQ index in 64% of patients and a better EQ-D QOL scores in 16%.

Conclusion. The majority of RA patients who came to the rheumatologists showed high to moderate disease activity. This was due to long disease duration, inadequate MTX dose, and insufficient patient monitoring in real clinical practice. Introduction of a computer system for selfassessment of their health status by RA patients in an outpatient setting could improve the interaction of physicians, nurses, and patients, better monitor disease activity, and enhance therapeutic efficiency. 

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a main tool to treat acute nonspecific low back pain (NLBP). However, no factors that influence the efficacy of these drugs have been identified to the present day.

Objective: to evaluate the therapeutic effect of and tolerance to NSAIDs (meloxicam) in treating acute NLBS and to identify the factors influencing the efficacy of this drug.

Patients and methods. A study group consisted of 2078 patients (mean age 46.3±13.4 years; women 56.6%) with acute NLBS who had been treated in real clinical practice. The level of pain was estimated using a 0–10 point numerical rating scale (NRS). Initially, the pain level averaged 6.69±1.65 scores; 57.0% of patients were noted to have severe pain (≥7 NRS scores). Pain at rest persisted in 32.0% of patients; that at night was in 19.0%; sensation of stiffness in 60.7%, irradiation to the leg in 28.2%, and lumbar ischialgia in 9.6%. 70.2% of patients had been previously treated with NSAIDs for NLBS, while only 28.0% rated their efficacy as good. All the patients were prescribed meloxicam at a dose of 15 mg/day for a period of up to 2 weeks. 86.1% of the patients received meloxicam intramuscular for 2 days, then orally; 13.9% took the drug only orally. 52.3% of the patients also used muscle relaxants; 17.4% received oral or intramuscular B vitamins. The study estimated the rate of complete pain relief when NSAIDs were used for up to 2 weeks.

Results and discussion. Complete pain relief was achieved in 75.2% of patients. 83.7% of patients rated the effect of treatment as good or excellent. Undesired drug reactions were recorded in 4.6% of patients. Female gender had no effect on treatment outcome (odds ratio (OR)=0.967; 95% confidence interval (CI), 0.795–1.177; p=0.763). Age over 65 years, the first NLBS episode, and a good NSAID effect in a history were associated with the best treatment result: OR=2.053 (95% CI, 1.5920–2.642), p<0.001; 1.415 (1.09–1.836), p=0.009; and 1.937 (1.513–2.481), p<0.001, respectively. Severe pain (≥7 NRS scores), persistent pain at rest and at night, and especially lumbar ischialgia indicated the worst result: OR=0.481 (95% CI, 0.393–0.588), p<0.001; 0.559 (0.441–0.709), p<0.001; 0.511 (0.413–0.631), p<0.001; and 0.346 (0.256–0.466), p<0.001, respectively. NSAIDs in combination with muscle relaxants and B vitamins versus NSAID monotherapy did not increase the likelihood of pain relief: OR=0.827 (95% CI, 0.594–0.889), p=0.02 and 0.917 (0.804–1.1201), p=0.452, respectively.

Conclusion. Meloxicam at a dose of 15 mg/day is an effective and safe drug to treat acute NLBS. Patient gender has no effect on treatment outcome. Age over 65 years, the first NLBS episode, and a good response to NSAIDs in a history are associated with the best treatment results; and severe pain, persistent pain at rest and at night, irradiation to the leg, and lumbar ischialgia are related to the worst result. NSAIDs in combination with muscle relaxants and B vitamins did not improve treatment outcomes. 

The most common operation for knee osteoarthritis (OA) is total knee arthroplasty (TKA); however, the latter is associated with the development of severe complications. This was the reason for the revival of the interest of orthopedic traumatologists in high tibial osteotomy (HTO), the essence of which is to transfer the load away from the affected medial part of the knee joint (KJ) to the intact lateral one.

Objective: to evaluate the medium- and long-term results of open-wedge (OW) HTO in primary and secondary I–III stage knee OA.

Patients and methods. The Laboratory of Orthopedic Rheumatology and Rehabilitation, V.A. Nasonova Research Institute of Rheumatology, performed 10 OW HTOs in 9 patients in 2005 to 2009 and 21 more OW HTOs in 19 patients in 2014 to 2018 (a total of 31 operations). The male/female ratio was 2.5:1. The mean age of the patients was 57.6±12.5 years; the body mass index (BMI) was 28.5±3.6 kg/m2 ; the correction angle was 11.7±2.5°. Preoperative planning was performed using the Miniaci method; the X-ray stage of knee OA was evaluated according to the Kellgren–Lawrence classification. OW HTO was carried out. For assessment of its results, the investigators determined the degree of pain using a visual analogue scale (VAS) and the KJ status by the Knee Society Score (KSS) scale. The results were assessed at one (n=31), 3.5±0.6 (n=28), and 8.5±1.3 (n=10) years.

Results and discussion. There was a tendency to worsen surgical results over time. The mean VAS values for pain at 1, 3.5, and 8.5 years were as follows: 9.8±10.3; 21.2±16.2 and 38±15.5 mm, respectively. In the same periods, the KSS functional scores were 83.6±14.8, 85.2±12.6, and 80.5±14.2; the objective scores were 80.7±8.5, 75.2±12.7, and 67.8±16.3. There was a strong correlation between the severity of pain and the functional and objective KSS scores (-0.78, -0.81 years, and -0.91 at 1, 3.5, and 8.5 years, respectively; p<0.05). At 3.5±0.6 years, the survival rate after OW HTO was 96.6%. None of the patients examined at 8.5±1.3 years after OW HTO needed TKA. The surgical result was studied in 2 patients at 14 years; one patient underwent TKA, the other refused surgical intervention, the result was satisfactory.

Conclusion. OW HTO has limited indications for use. However, in patients who are allowed to undergo this operation, pain syndrome can be relieved, by maintaining and/or improving KJ function; in most cases, TKA can be delayed for more than 10 years. 

Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology, which is characterized by chronic erosive arthritis (synovitis) and systemic inflammation of the viscera. Methotrexate (MTX) is the drug of choice for RA treatment. However, it is currently impossible to predict the efficacy of MTX in a particular patient; the drug fails to produce the desired effect or causes adverse reactions in a considerable number of patients. The identification of patients who are responsive to MTX could significantly improve the results of therapy.

Objective: to investigate the specific features of baseline (pretreatment) expression of genes responsible for major metabolic and energy production pathways in RA patients with different disease activity and to identify the genes, the baseline expression of which could serve as a predictor for remission attainment.

Patients and methods. Blood from 40 RA patients (mean age 47.5 years; mean disease duration 7.9 weeks) who had not previously received MTX and 26 healthy donors (mean age 45.1 years). All the patients had used MTX (15 mg/week) for 2 years. Clinical response was evaluated by DAS28 and the serum levels of anti-cyclic citrullinated peptide antibodies, C-reactive protein, and rheumatoid factor. Remission was diagnosed according to ACR/EULAR and DAS28 (DAS28 <2.6). Joint structural changes were radiographically evaluated. Gene expression was determined in peripheral blood cells by real-time reverse transcriptase-polymerase chain reaction. A control group consisted of 26 randomly recruited gender- and sex-matched patients without autoimmune diseases and a family history.

Results and discussion. MTX treatment significantly decreased disease activity according to DAS28. At the end of the investigation, the majority of patients had moderate disease activity (3.2≤ DAS28 ≤5.1), 4 had high disease activity, while 12 attained remission (DAS28 <2.6). Gene expression analysis showed that RA patients who had achieved clinical remission after MTX therapy displayed higher baseline expression of the genes associated with glycolysis (Glut1, PKM), inflammation (TNF-α), autophagy (ULK1), apoptosis (caspase 3, p21), and hypoxia (HIF1α), compared with patients who had not attained remission and with healthy individuals. In addition, in patients who had achieved remission, the baseline expression of the CD1 gene was significantly higher than in healthy individuals, while in the remaining patients the expression of this gene was significantly lower than in the controls. While the disease activity remained high, the baseline expression of the p21, caspase 3, TGFβ1, and RUNX2 genes was significantly lower than in healthy individuals and other patients with RA.

Conclusion. Remission achievement in RA patients who had not previously received MTX was associated with higher baseline (pretreatment) gene expression associated with glycolytic activity, inflammation, autophagy, apoptosis, and hypoxia compared with patients who failed to attain remission. Elevated baseline expression of the CD1 gene compared with that in healthy individuals may serve as a predictor of sensitivity to MT therapy. 

Family and twin studies have shown that ankylosing spondylitis (AS) has a hereditary nature that is based on a strong association with the leukocyte antigen HLA-B27. However, only 1–5% of HLA-B27 carriers develop AS, which indicates that there are other genetic markers involved in the formation of a predisposition to this disease. A number of genome-wide association studies have convincingly confirmed the role of the STAT4 gene. This gene encodes the protein – the signal transducer and activator of transcription (STAT) protein, which is a predisposing factor for the development of many autoimmune diseases. There are not so many studies of the relationship of STAT4 polymorphisms to the predisposition to AS, and there are no these studies regarding the Russian population.

Objective: to study whether there is a possible association of STAT4 rs7574865 gene polymorphism with the predisposition to AS and to assess the activity of this disease using BASDAI and ASDAS scores in the Russian patient population.

Patients and methods. A cohort of 203 individuals, including 100 patients (79 men and 21 women) with AS, and 103 healthy volunteers (a control group) was surveyed. Age, gender, duration, and specific features of AS onset, ESR, and CRP levels were assessed. BASDAI and ASDAS scores were calculated to evaluate disease activity.

Results and discussion. There was a significant relationship between STAT4 polymorphism and C-reactive protein (CRP) levels and BASDAI and ASDAS-CRP scores. The TT genotype carriers had significantly higher mean activity indices compared to the GG (p=0.001) and GT (p=0.005) genotype carriers for CRP, BASDAI (p=0.0001 and p=0.009, respectively) and ASDAS-CRP (p=0.009 and p=0.001, respectively). High disease activity (BASDAI >4 and ASDAS-CRP >3.5) was also associated with the high frequency of the T allele (p=0.046 and p=0.004, respectively). The value of STAT4 rs7574865 gene polymorphism in the pathogenesis of autoimmune diseases is confirmed by a study in which the T allele in STAT4 rs7574865 enhances mRNA transcription and protein expression. Italian authors have shown that there is a relationship between the minor T allele of rs7574865 and the high risk of arthritis. We have previously established a relationship between the T allele and the predisposition to diffuse systemic scleroderma, interstitial lung damage, and elevated anti-topoisomerase I antibody levels.

Conclusion. The present study has shown for the first time a significant association of STAT4 rs7574865 polymorphism with the main AS activity indicators: CRP levels, BASDAI and ASDAS-CRP scores. The studied polymorphism may be a new genetic marker for predicting the severity of AS. 

The onset of ankylosing spondylitis (AS) more frequently occurs at the end of the third decade of life, which corresponds to the time of marriage and the birth of the first child and determines the relevance of a study of the interaction of AS and pregnancy.

Objective: to describe the clinical presentations of AS and its therapy during pregnancy and to study AS activity dynamics and the patients' functional status during gestation.

Patients and methods. The investigation enrolled 19 pregnant women who met the 1984 modified New York AS criteria. The mean age of the women was 32.2±1.1 years; their mean age at the onset of AS was 22.6±3.1 years; the duration of the disease was 147±20.7 months. The patients visited their physician at 10–11, 20–21, and 31–32 weeks of pregnancy. The investigators determined AS activity by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS) and functional status by the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Metrology Index (BASMI). The Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) was used to assess enthesitis.

Results and discussion. At the time of conception, 78.9% of the patients had inflammatory back pain with an intensity of 2.2±0.4 on a numerical rating scale; during pregnancy, 95% of the pregnant women experienced pain, its intensity increased by the second trimester (4.6±0.7) and remained at this level in the third trimester (p<0.05 between the month of conception and the second and third trimesters). By the third trimester, the nature of the pain changed: 55.5 and 61.1% of the patients reported reduced pain at rest and after exercise, respectively. The frequency and severity of enthesitis increased with gestational age: the MASES scores were higher in the third trimester (2.3±0.5) than that in the first-trimester (0.4±0.22; p<0.05). The frequency of extra-axial and extra-skeletal manifestations did not increase during gestation. Coxitis was detected in 27.8% of the pregnant women.

The BASDAI increased from the time of conception (1.7±0.3) to the second trimester (3.3±0.5; p<0.05) and remained at this level in the third trimester. Multiple regression analysis revealed that the predictors of BASDAI levels in the third trimester were BASDAI scores (R2 =0.7) and back pain (R2 =0.9) at the time of conception, the use of biological agents 3 months before gestation (R2 =0.7) with their cumulative impact. Throughout pregnancy, the BASDAI was determined by a set of factors: the severity of pain in the back (β=0.6) and entheses (β=0.3) and weakness (β=0.6). By the end of the first trimester, the increased BASDAI scores were provided mainly by the higher level of general weakness (by 68.5%) and back pain (by 24.1%). In the second trimester, the higher BASDAI was due to the increased severity of enthesitis (by 30.7%) and back pain (by 27%).

There were no changes in ASDAS-C-reactive protein (ASDAS-CRP), but there was its upward tendency in the second trimester as compared with the beginning of pregnancy. The BASMI did not change significantly (1.3±0.9; 1.8±0.2; 2.1±0.3, respectively, for trimesters). The BASFI increased by the third trimester (3.9±0.7) versus the first trimester (1.4±0.3; p<0.05).In the third trimester, this rise was due to difficulties in performing the actions related to both AS activity and pregnancy (forward bends; questions 1, 2, and 4).

According to the trimesters, 31.6, 73.7, and 66.7% of the pregnant women took nonsteroidal anti-inflammatory drugs. The need for glucocorticoids was noted in 22% of patients in the second trimester and in 53% in the third trimester.

Conclusion. The clinical activity of AS is increased by the second trimester of pregnancy and remains moderate and high until the end of gestation. The activity of AS at the time of conception can determine the activity of the disease throughout pregnancy. In the third trimester, mechanical back pain becomes concurrent in half of the patients. Functional impairments increase with gestational age, and this is due to both the activity of AS and pregnancy itself in the third trimester. 

The incidence of ankylosing spondylitis (AS) has recently increased with a substantial rise in the proportion of female patients, making this investigation relevant.

Objective: to investigate the clinical and laboratory parameters of inflammatory activity and functional status in male and female patients with AS at different stages of the disease.

Patients and methods. Examinations were performed in 119 patients (82 men and 37 women) (mean age, 36.4±0.9 years) with AS and 34 patients (24 men and 10 women) (mean age 27.0±1.6 years) with non-radiographic axial spondyloarthritis (nr-axSpA). The investigators used the 1984 modified New York criteria to confirm AS diagnosis and the 2009 ASAS classification criteria for axial spondyloarthritis. They also determined AS activity by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and functional status by the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Metrology Index (BASMI). For the calculation of enthesites, the validated index Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) was used; pain intensity in the last week was estimated using a visual analogue scale (VAS). Laboratory examination included the determination of ESR and HLA-B27 antigen. All the patients underwent a plain film of the pelvic bones; and patients with nr-axSpA had magnetic resonance imaging for sacroiliitis.

Results and discussion. In both groups, there was a male preponderance and axial lesions were more common (among the patients with AS, there were 68.9% of the men with sacroiliac joint lesions and 53.7% of those with spinal involvement; among the patients with nr-axSpA, there were 80.0 and 67.6 %, respectively; p>0.05). The HLA-B27 antigen was detected in the majority of patients with AS (86.6% of men and 91.7% of women) and in those with nr-axSpA (91.6 and 80.0%, respectively). Uveitis was more common in women with AS (32.4%), less common in men with AS (17.1%); (p<0.05) and nr-axSpA (8.3%); uveitis was not observed in women with nr-axSpA (p<0.001). The pain according to VAS was more intense in women (48.1±3.4 mm; p<0.01); in the nr-axSpA group, its values were comparable in men and women (p>0.05). The BASDAI and BASFI scores were similar in women at all stages of the disease (p>0.05). The men with nr-axSpA had the best functional status (p<0.01) with the same BASDAI activity (p>0.05) compared with those with AS. The BASMI in patients with AS regardless of gender was higher than in those with nr-axSpA (p<0.01). High BASDAI activity was more frequently detected in women with AS and nr-axSpA than in men (64.9 and 60.0%, respectively; p<0.01). Low activity was not observed in any woman with nr-axSpA. Enthesitis was more common in women in both AS and nr-axSpA (81.0 and 80.0%, respectively; p<0.05).

Conclusion. In women, AS and nr-ax-SpA are more severe, starting at their early stage, which is manifested by a higher activity, functional failure, and a higher frequency of extra-axial manifestations. 

Objective: to analyze the efficacy of tofacitinib (TOFA) in patients with an advanced stage of rheumatoid arthritis (RA) and previous methotrexate (MTX) failure according to comprehensive clinical and laboratory examination.

Patients and methods. Nineteen patients (11 women and 8 men aged 29 to 71 years (mean age 53.47±10.53 years)) with a reliable diagnosis of RA according to the 2012 American College of Rheumatology (ACR) criteria were followed up. Due to a high disease activity (DAS28 averaged 5.84±0.89), the patients were prescribed TOFA 10 mg/day taken for 12 months. The disease activity indicators were assessed at baseline, 3, 6, and 12 months after the start of the study.

Results and discussion. The effect of TOFA developed quite quickly: at 3 months of therapy, there were positive clinical, laboratory, and instrumental changes in most patients; 5 (26.3%) patients achieved the goal of treatment. At 12 months of therapy, 8 patients achieved DAS28 remission and 3 patients had a low disease activity; moderate RA activity persisted in 7 patients; and a high disease activity was seen in 1 patient; these SDAI activity indicators were observed in 2, 8, 7, and 2 patients, respectively. According to the ACR criteria, 20, 50, and 70% improvements were achieved by 8, 6, and 3 patients, respectively. No serious adverse reactions were recorded. The findings confirm the good efficacy and safety of TOFA in the treatment of patients with an advanced stage of RA.

Conclusion. The innovative mechanism of TOFA allows a significant number of patients, in whom MTX therapy was not effective enough, to achieve the goal of treatment. 

Objective: to compare the frequency of clinical manifestations of Behcet's disease (BD) in patients of both sexes in a Russian cohort.

Patients and methods. Examinations were made in 425 patients (285 men and 140 women; mean age, 33.2±10.2 years; median duration of BD, 134.3 [60.0; 192.0] months (about 11 years) with a reliable diagnosis of the disease. 208 (48.9%) patients were ethnic residents of the North Caucasus. The activity of BD was assessed using the BD Current Activity Form; the disease severity was evaluated according to the classification proposed by Ch. Zouboulis.

Results and discussion. In men with BD in the Russian cohort, the activity and severity of the disease were significantly higher and the HLA-B5(51)- antigen was more common. There was an association of male sex with thromboses in the deep cerebral veins and cerebral sinuses, damage to the eyes and skin (pseudopustulosis and pseudofolliculitis), genital ulcers, and a positive pathergy test. The findings are consistent with the results of studies of other patient cohorts: Iranian, German, Turkish ones, in which the men were more frequently detected to have damage to the vessels, skin and eyes.

Conclusion. In the Russian patient cohort, the male sex is associated with high BD activity, severe organ damages, and HLA-B5(51)-antigen positivity, which is the basis for prescribing immunosuppressive therapy in men with early-stage BD. 

Osteoarthritis (OA) is a heterogeneous disease with varying degrees of inflammatory responses, structural changes, functional insufficiency, and disease progression as a whole. Some OA phenotypes are characterized by a high local inflammatory response, persistent pain, persistent synovitis, and severe functional limitation. As a rule, the use of traditional nonsteroidal anti-inflammatory drugs in these patients and the injection of glucocorticoids into the joint show no substantial effect. Taking into account the important role of inflammation and the involvement of immune responses in the pathogenesis of OA, the existence of its erosive forms, the use of some disease-modifying anti-rheumatic drugs could be a rational solution of the problem in the therapy of this disease.

The paper reviews data on the efficiency and safety of using methotrexate and hydroxychloroquine in OA. 

Osteoarthritis (OA) is the most common disease of the musculoskeletal system, which is characterized by persistent pain, joint dysfunction, and early disability. The incidence of OA has now increased, and, according to the data obtained by the V.A. Nasonova Research Institute of Rheumatology, amounts to about 13%, which is 5 times higher than official statistics. The major goals of OA treatment are aimed at reducing pain, improving the functional state of the joint, preventing the development of joint deformity, improving the quality of life of patients, and minimizing the side effects of pharmacotherapy. Intra-articular hyaluronic acid (HA) injections have been long used as a synovial fluid prosthesis; however, recently published studies have provided new data on the mechanisms of action of these drugs and the role of this method in the treatment of patients with OA. Numerous meta-analyses have shown that HA therapy does not substantially differ from placebo in tolerance, thereby ensuring significantly reduced pain and improved joint function. This review deals with some issues of intra-articular HA administration in patients with OA, with the mechanisms of action of HA preparations, with the problems of choosing a drug according to its source, molecular weight, administration methods, and the efficiency of the therapy compared to other drugs.

The review contains data from large-scale foreign and Russian studies of the epidemiology of osteoarthritis (OA). It considers the role of modifiable and non-modifiable risk factors for OA, such as age, sex, hormonal status, obesity, etc. There are data on genetic susceptibility to OA and on congenital anomalies that contribute to joint structural changes. Data on the impact of racial and ethnic factors on the development and progression of OA are analyzed. The role of metabolic disorders in the pathogenesis of this disease is highlighted. Data on the relationship of OA to patients' professional activities are summarized.

The paper reviews of the data available in the literature on the clinical efficacy and safety of tofacitinib (TOFA) in the treatment of psoriatic arthritis (PsA). It considers the mechanism of action of TOFA, which is mainly in the selective inhibition of signal transmission due to its effect on the activity of JAK3 and/or JAK1, the enzymes that ensure the function of turning on and turning off the signals transmitted by cytokines. TOFA is noted to directly or indirectly act on a wide range of a number of molecules that play an important role in the pathogenesis of PsA.

The paper analyzes the current data on the clinical efficacy of TOFA in treating PsA, which have been obtained in the 12-month OPAL Broaden study including patients with PsA and an inadequate response to synthetic disease-modifying anti-rheumatic drugs and in the 6-month OPAL Beyond study enrolling those with PsA and an inadequate response to tumor necrosis factor-α (TNF-α) inhibitors. It is noted that the results of these studies confirmed the efficacy of the drug in treating PsA not only according to the data of objective (medical) monitoring, but also to the subjective characteristics of pain, to the global assessment of disease activity, fatigue, as well as the mental and physical components of the SF-36 quality of life questionnaire.

It is concluded that the current findings allow JAK inhibitors to be recommended as a new pathogenetically sound approach to treating PsA and suggest that TOFA has benefits in managing patients unresponsive to therapy with TNF-α inhibitors. 

Cystic and bullous lung transformation occurs in diseases of various origins: neoplastic, genetically determined, rheumatic, lymphoproliferative, and infectious diseases. The paper presents a review of the literature and a clinical case of a young female patient with a long history of Sjögren's disease. Fifteen years after the onset of the disease, the patient developed cystic and bullous lung transformation and renal angiomyolipoma, which are regarded as a manifestation of probable lymphangioleiomyomatosis.

The paper deals with the debatable problem due to a lack of consensus in the medical literature regarding the formulation of the diagnosis of Felty's syndrome that is rheumatoid arthritis with extra-articular (hematological) manifestations.

The paper presents the results of a survey of 846 Russian physicians (neurologists, rheumatologists, orthopedic traumatologists, general practitioners, and therapists), whose work is associated with the treatment of musculoskeletal pain. The physicians have been asked to answer which topics they consider important for their education. It turns out that the first place is occupied by the issues of differential diagnosis of the most common musculoskeletal diseases and current methods for their treatment (interventional methods in particular), as well as the problems of rational use of nonsteroidal anti-inflammatory drugs. More than half of the respondents find it interesting to discuss the legal aspects of a physician's work.