The Coronavirus Disease 2019 (COVID-19) pandemic has drawn closer attention than ever before to the problems of the immunopathology of human diseases, many of which have been reflected when studying immune-mediated inflammatory rheumatic diseases (IIRDs). The hyperimmune response called a cytokine storm, the pathogenetic subtypes of which include hemophagocytic lymphohistiocytosis, macrophage activation syndrome, and cytokine release syndrome, is among the most serious complications of IIRDs or treatment for malignant neoplasms and may be a stage of COVID-19 progression. A premium is placed to interleukin-6 (IL-6) in the spectrum of cytokines involved in the pathogenesis of the cytokine storm syndrome. The clinical introduction of monoclonal antibodies (mAbs) that inhibit the activity of this cytokine (tocilizumab, sarilumab, etc.) is one of the major advances in the treatment of IIRDs and critical conditions within the cytokine storm syndrome in COVID-19. The review discusses data on the clinical and prognostic value of IL-6 and the effectiveness of anti-IL-6 receptor and anti-IL-6 mAbs, as well as prospects for personalized therapy of the cytokine storm syndrome in COVID-19.

Objective: to analyze the results of tofacitinib (TOFA) therapy in real clinical practice according to the All-Russian Arthritis Registry (OREL).
Subjects and methods. The OREL Registry included 347 patients (286 (82%) women and 61 (18%) men) with rheumatoid arthritis (RA) who initiated TOFA therapy. The male:female ratio was 1:4.7. The patients’ median age at onset of the disease was 42 years; its duration was 8 years. Most of the patients included in the registry had extended- (n=171 (52%)) or late- (n=148 (45%)) stage of RA.
Results and discussion. Prior to initiation of TOFA therapy, RA activity according to DAS28 was high and moderate in 91 (64.5%) and 40 (28.4%) patients, respectively; the median DAS28 value was 5.5 [4.6; 6.2]; SDAI – 30.5 [21.4; 42.9], and CDAI – 28.2 [20.0; 37.1]. The use of TOFA was accompanied by significant decrease of disease activity. After 12 weeks, high RA activity was persistent in 32 (22.7%) patients; the number of patients with moderate activity increased to 77 (54.6%), that of those with low activity rose to 15 (10.6%); remission was observed in 17 (12.1%) patients. 216 (62.6%) and 76 (22%) patients received TOFA as first- and second-line therapy, respectively. TOFA was most frequently prescribed when tumor necrosis factor-á inhibitors (19.6%), rituximab (7.8%), tocilizumab (4.3%), and abatacept (5.2%) were insufficiently effective or poorly tolerated.
Conclusion. The results of using TOFA in real clinical practice may suggest that the drug has high efficacy in patients with RA. TOFA can be used at a dose of 5 or 10 mg twice daily as both alone and in combination with disease-modifying anti-rheumatic drugs. TOFA showed similar efficacy in patients who had earlier taken biological agents and in those who had not.

Objective: to evaluate the clinical efficacy and safety of the targeted synthetic disease-modifying anti-rheumatic drug (DMARD) tofacitinib (TOFA; Yakvinus®) in patients with active psoriatic arthritis (PsA) at 12 and 24 weeks after starting treatment. To define the place of TOFA in the therapy of PsA patients.
Subjects and methods. Examinations were made in 41 patients (17 men and 24 women) with active PsA and an insufficient response to previous treatment with synthetic DMARDs and/or biological agents (BA). Before starting therapy, the median disease activity for psoriatic arthritis (DAPSA) and disease activity score (DAS28) were 44.2 [37.8; 55.3] and 5.5 [4.7; 6.1], respectively. TOFA tablets were prescribed at a dose of 5 mg twice daily for 24 weeks with possible dose escalation to 10 mg twice daily after 12 weeks. At the beginning of the investigation, at 12 and 24 weeks, the investigators assessed disease activity and TOFA therapy efficiency of according to DAPSA, DAS28 and minimal disease activity (MDA) criteria: tender joint count ≤1, swollen joint count ≤1, a psoriasis area severity index (PASI) ≤1 or body surface area (BSA) ≤3%, pain intensity ≤15 mm, patient global assessment ≤20 mm, Health Assessment Questionnaire (HAQ) ≤0.5, and enthesitis ≤1. They also determined the number of patients who had achieved remission (DAPSA ≤4, DAS28 score <2.6), low disease activity (DAPSA 5-14, ≤2.6, DAS28 <3.2) or MDA (5 out of the 7 criteria) during TOFA therapy at 24-week follow-up. The safety of therapy was evaluated by analyzing the drug-induced adverse events (AE): the frequency, severity and time of their occurrence were studied.
Results and discussion. At 24 weeks after initiation of TOFA therapy, there was a significant decrease of median DAPSA and DAS28 values as compared to baseline, to 11 [4.3; 17.3] and 2.6 [1.7; 3.4] respectively. The median Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) also significantly decreased from 6 [4.2; 7] and 3.8 [2.8; 4.4] to 1.4 [0.6; 3.2] and 1.5 [1; 2.1] respectively. The median BSA was significantly reduced from 3 [1; 5] to 0.5 [0.1; 2]. At 24 weeks after initiation of TOFA therapy, DAPSA and DAS28 low disease activity/remission were achieved by 38.5/23.1% and 17.9/53.9% of patients, respectively. Fifteen (38.5%) patients achieved MDA. 38 (92.7%) of the 41 patients completed a full TOFA therapy cycle. Two patients dropped out of the investigation due to ineffective therapy and one due to AE (diarrhea occurring up to 10 times daily, headache, elevated blood pressure, and lacrimation). At 24 weeks, 14 (34.2%) patients reported to have AE. The most common AE noted in 7 (17.1%) patients were infections: acute respiratory viral infection (n=3), fever (n=2), and folliculitis (n=2). In addition, two patients had diarrhea and two had headache.
Conclusion. TOFA is an effective drug for the treatment of PsA patients with moderate or high inflammatory activity, has a significant effect on all clinical manifestations of PsA and has a satisfactory safety profile.

Objective: to investigate the correlation of bone mass, the parameters of vascular stiffness and subclinical atherosclerosis with biochemical markers of inflammation in postmenopausal women.
Subjects and methods. The cross-sectional investigation included 98 patients aged 45–82 years who were followed up in the outpatient setting and signed an informed consent. The investigation did not include patients with any clinical manifestations of atherosclerosis, malignant neoplasms, with diseases causing secondary osteoporosis, as well as with the presence of symptoms of acute bacterial or viral infections and an exacerbation of chronic diseases, who took drugs affecting bone metabolism and vascular stiffness. C-reactive protein (CRP) level was determined by a high-sensitive immunoturbidimetric assay using carboxylated polystyrene particles. interleukin (IL)-6 concentration was measured by an enzyme immunoassay. The intima-media thickness (IMT), the presence and number of atherosclerotic plaques (ASP) were studied with duplex scanning. Pulse wave velocity (PWV) and augmentation index (AI) were measured by applanation tonometry using a SphygmoCor device (AtCor Medical Pty. Ltd., Sydney, Australia). Lumbar spine and hip bone mineral density (BMD) was determined using dual energy X-ray absorptiometry.
Results and discussion. There was an increase in the parameters of vascular stiffness, subclinical atherosclerosis, and CRP level and a decrease in bone mass with a longer length of menopause. The vascular stiffness parameters, including IMT (r=0.26; p<0.05), AI (r=0.25; p<0.05), the presence of ASP (r=0.24; p<0.05), and PWV (r=0.23; p<0.05), directly correlated with CRP level. A negative correlation was found between LI–IV BMD and CRP (r=-0.31; p<0.05). The probability of detecting increased IMT with a high CRP level was increased by 2.64 times, ASP by 3.18 times, and low BMD by 2.4 times. There was no association of bone mass, and the parameters of subclinical atherosclerosis and vascular stiffness with IL-6.
Conclusion. Lower bone mass and the development of osteoporosis in postmenopausal women were associated with increased vascular stiffness and the presence of signs of subclinical atherosclerosis, and with a high level of CRP, which allows one to discuss the common mechanisms for development of osteoporosis and atherosclerosis, as well as the involvement of chronic inflammation in them.

Objective: to analyze the association of the polymorphic marker rs4537545 (C>T) in the IL6R gene with the development of rheumatoid arthritis (RA) in the population of the Republic of Karelia.
Subjects and methods. The investigation included 190 samples of DNA extracted from the whole blood of healthy individuals and 158 samples from patients with RA. Genotyping was performed using a polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis. The expression level of IL6 and IL6R genes in peripheral blood leukocytes (PBLs) from healthy individuals was assessed by real-time PCR. The plasma content of interleukin-6 (IL-6) in healthy donors was measured by enzyme-linked immunosorbent assay (ELISA).
Results and discussion. An association of the polymorphic marker rs4537545 (C>T) in the IL6R gene with the development of rheumatoid arthritis was found in the population of the Republic of Karelia. The risk of RA in the persons carrying the T-allele of rs4537545 in the genotypes was 2.1 times higher than that in the C-allele carriers (odds ratio (OR), 2.103; 95% confidence interval, 1.032-4.287). The genotypes were ascertained to have an effect on the level of IL6R gene in PBL and on the plasma content of IL-6 in the healthy donors.
Conclusion. The polymorphic marker rs4537545 (C>T) in the IL6R gene is involved in the genetic predisposition of humans to RA development through modulation of the level of transcriptional activity of the IL6R gene and the content of IL-6.

The development of microcrystalline arthritides is most frequently associated with the formation of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals. Their identification is of crucial importance in recognizing these diseases.
Objective: to determine the possibilities of histological techniques in identifying MSU and CPP crystals and to evaluate the effectiveness of the techniques.
Subjects and methods. Twenty-four tissue blocks (fragments of the affected areas of the elbow joint, the interphalangeal joint of the index finger, and hip joint) from 7 patients were examined. Paraffin sections were stained with a 0.5% alcohol solution of eosin, as well as with hematoxylin and eosin. Tissue specimens were examined and digitized using an AxioScope.A1 stereo microscope with Zenblue software (Carl Zeiss MicroImaging GmbH, Germany).
Results and discussion. When staining the tissue sections with hematoxylin and eosin, microcrystals were not visualized; the major portions of MSU crystals was dissolved during fixation and staining, whereas CPP crystals were masked with hematoxylin as focal basophilic aggregates. The staining technique with an alcohol solution of eosin and short formalin fixation (within 12 hours) made it possible to avoid dissolution of MSU crystals and to visualize both MSU and CPP crystals, and to determine their shape and color.
Conclusion. Light microscopy of the tissue sections stained with an alcohol solution of eosin along with short formalin fixation is a reliable method to differentiate MSU and CPP crystals. In patients undergoing endoprosthetic replacement, the significance of this technique for the pathomorphological study of surgical material consists in assessing inflammatory activity and in eliminating a disease, such as microcrystalline arthropathy.

Diabetic osteopathy is one of the little studied complications of diabetes mellitus (DM), which leads to common lowtrauma fractures and, as a consequence, disability and death. The level of insulin is connected with bone functional and morphological changes followed by decreased bone mineral density (BMD) in the early stages of diabetic osteopathy.
Objective: to study bone morphofunctional properties in males with type 1 and 2 DM (T1DM and T2DM).
Subjects and methods. Examinations were made in 41 male patients with T1DM and 52 male patients with T2DM without a history of fractures. Their age varied from 40 to 70 years (mean age, 55.8±0.7 years and 58.4±0.9 years, respectively). A control group consisted of 34 patients (mean age, 55.9±0.9 years) without a history of DM. Patients with other endocrine disorders, end-stage complications, or chronic liver and kidney diseases were excluded from the investigation. BMD was determined by dual-energy X-ray absorptiometry (DXA). Serum bone remodeling markers (procollagen type 1 amino-terminal propeptide and C-terminal telopeptide), as well as 25(OH)D, parathyrin, insulin, glycated hemoglobin (HbA1c), and electrolytes (Ca2+, P+) were evaluated.
Results and discussion. An association of BMD with renal function, HbA1c, and body mass index was observed in patients with T2DM. In the T1MD group, BMD was closely related to insulin deficiency and was significantly lower than that in the control group. In patients with vitamin D deficiency, BMD was significantly lower than in those with normal vitamin D levels (p<0.05). The patients with T1DM displayed both a decrease in BMD (p<0.05) and a pronounced change in the levels of bone markers (p<0.05). Those with T2DM had impaired bone remodeling processes, which was determined by the level of these markers (p<0.05) and observed in the presence of normal BMD due to the complex pathophysiology of the underlying disease.
Conclusion. Vitamin D deficiency, insufficient and decreased insulin sensitivity, hyperglycemia, and overweight are important causes of osteopathy in patients with DM. The markers of bone remodeling may become promising indicators for diagnosing osteopathy, but additional studies are needed to elaborate recommendations for their use in routine practice in order to predict and prevent this complication of DM.

Autoimmune diseases, including rheumatoid arthritis (RA), are risk factors for thrombotic events. Understanding the pathogenetic role of hemostatic changes in RA can assist in developing measures for prevention, prognosis, early diagnosis, and treatment of immune thromboses.
Objective: to investigate the state of platelet and plasma hemostasis in patients with RA, as compared to other laboratory parameters and clinical manifestations of the disease.
Subjects and methods. Hemostasis was investigated using two relatively new laboratory tests: thrombodynamics and kinetics of blood clot contraction (BCC). Examinations were made in 60 patients with RA and in 50 apparently healthy individuals of the control group.
Results and discussion. In patients with RA, the parameters of thrombodynamics and BCC were found to be significantly different from the normal values. According to thrombodynamics, there was an increase in plasma clot growth rate, size, and density, which indicates chronic hypercoagulation. The rate and completeness of BCC were substantially reduced due to platelet dysfunction in patients with RA compared to healthy individuals. The changes in the parameters of thrombodynamics and BCC correlated with the laboratory signs of systemic inflammation and depended on the radiographic stage of the disease.
Conclusion. The results of this investigation confirm that hemostatic disorders are present in RA and indicate the informative value of thrombodynamics and BCC tests as indicators of a pre-thrombotic state, including autoimmune pathology.

Deciphering the mechanisms of the pathogenesis of immune-mediated inflammatory rheumatic diseases (IMIRDs) in conjunction with designing a wide range of biological agents is one of the major medical advances in the 21st century. A new promising area of pharmacotherapy for IMIRDs is associated with the design of the so-called targeted oral medications that primarily include Janus kinase (JAK) inhibitors. The review presents new data on the efficacy and safety of the new JAK inhibitor baricitinib in treating rheumatoid arthritis and other IMIRDs.

The lecture considers the main stages of the creation and development of orthopedic rheumatology in Russia. It summarizes some results of the scientific and practical activities of orthopedic rheumatologists of the V.A. Nasonova Research Institute and discusses prospects for further scientific developments and the possible development of minimally invasive surgery, such as arthroscopic surgery of the large and small joints. Emphasis is placed on the rehabilitation of patients with rheumatic diseases, by using high-tech treatments.

Interleukin-5 (IL-5) is involved in the maturation and activation of eosinophils, its production is increased in patients with eosinophilic granulomatosis with polyangiitis (EGPA). This rare form of systemic vasculitides (SV) is characterized by peripheral eosinophilia and involves multiple organs and systems. The clinical introduction of glucocorticoids (GCs) and immunosuppressants has considerably improved the prognosis of EGPA, but their use is associated with significant adverse reactions and cannot be effective enough. The use of standard treatment regimens cannot always allow to achieve remission; the rate of EGPA relapses remains high. Mepolizumab is an IL-5 antagonist and a promising drug for the treatment of patients with EGPA. The presented literature review considers arguments in favor of using mepolizumab in EGPA patients and discusses its efficacy and safety. The currently accumulated data suggest that mepolizumab is effective and safe in treating patients with EGPA, what has been demonstrated in the registration double-blind, randomized, placebo-controlled MIRRA study. Treatment with the IL-5 antagonist allows one to control both the symptoms of asthma and the manifestations of SV, enhances the probability of achieving remission of EGPA, can help reduce the risk of relapse and minimize the dose of GS.

Patients with diabetes mellitus (DM) often show changes in the locomotor apparatus (LMA), in particular cheiroarthropathy, a specific lesion of the connective tissue structures of the hand in the presence of persistent hyperglycemia, which leads to limited joint mobility (LJM) generally in the absence of pain syndrome. Some authors use the term «LJM syndrome» to describe LMA lesion in DM, since in the long course of the disease, the small and large joints of not only the upper, but also the lower limbs are involved in the pathological process. LJM is one of the little studied and poorly diagnosed conditions in comparison with traditional micro- and macro-vascular complications of DM, which, due to their direct correlation with life expectancy, receive more attention. The LJM syndrome is associated with other late complications of DM and can significantly impair functional activity, self-care, and quality of life. Damages to periarticular tissue and joints in DM are believed to be caused by the accumulation of glycation end products. A clinical examination plays a key role in the diagnosis of cheiroarthropathy.

In addition to damage to the spine and joints in ankylosing spondylitis (AS), as in other diseases from a group of spondyloarthritides (SpA), there can be the following extra-articular manifestations: inflammatory bowel disease (IBD), uveitis, psoriasis, and kidney and heart diseases. In the last decade, much attention has been paid to the association between SpA and IBD; the common pathogenetic mechanisms of these diseases have been identified. The relationship between inflammation and blood coagulation has been known since ancient times, and its evidence base is constantly expanding. Both of these processes are accompanied by platelet activation and fibrin formation. The authors present a clinical case of a female patient with the comorbidity of AS with IBD and iliocaval thrombosis.

Currently, there is no clear data indicating the risk of specific complications when using non-steroidal anti-inflammatory drugs (NSAIDs), and in particular ibuprofen, for COVID-19 infection. There is also no clear clinical evidence that taking NSAIDs increases the risk of COVID-19 infection. However, when using NSAIDs in patients with acute respiratory viral diseases, keep in mind the possibility of class-specific complications from the gastrointestinal tract, cardiovascular system and kidneys. This risk is quite serious in elderly patients with multiple comorbid diseases. In addition, you should remember that taking NSAIDs and paracetamol can mask important symptoms of COVID-19 infection (in particular, fever) and lengthen the time for making a correct diagnosis.