Skin lesions in systemic lupus erythematosus (SLE) are not just a cosmetic defect, accompanied by a deterioration in the quality of life and psychological discomfort, but, possibly, the first sign of a systemic course of disease. Systemic involvement can develop in patients with almost any type of cutaneous lupus erythematosus (CLE), requiring the study of CLE in combination with SLE. Dermatologists are the first to face with skin manifestations of SLE, while other organs and systems affection leads the patient to a rheumatologist. It is important to understand that skin lesions do not cause irreversible organ damage, but continuity of therapeutic approaches between a dermatologist and a rheumatologist is necessary. The review presents the clinical signs, diagnostic features and histological characteristics of CLE.

The development of therapeutic drug monitoring of methotrexate (MT) remains an important and unresolved problem.

Objective: to study the dynamics of the concentration of MT metabolites in groups of patients with different responses to MT therapy, to identify the clinical features of these groups.

Patients and methods. The study included 79 patients with rheumatoid arthritis (RA), including 65 (82%) women and 14 (18%) men (mean age 53±11 years). MT monoglutamate was measured in erythrocytes (ER) and mononuclear cells (MO), as well as the main MT metabolites: polyglutamates with 2, 3 and 4 glutamate residues (MTPG2-4), as well as 7-hydroxymethotrexate (7-OH-MT) after 4, 12, 24 and 36 weeks after the start of MT treatment.

Results and discussion. Among the patients who completed the 24-week follow-up, 34 responded to MT therapy (Group 1) and 36 did not respond to it (Group 2). Patients of the two groups did not differ in the concentration of various metabolites of MT after 4 weeks, age, body mass index, duration of RA, DAS28 value, radiological stage, functional class, presence of extra-articular manifestations, single and cumulative doses of MT. In the 1st group after 12 weeks of therapy, a higher concentration of 7-OH-MT (ER) was detected, after 24 weeks – a higher concentration of 7-OH-MT (MO) and a lower level of MTPH3 (ER).

Conclusion. The concentration of 7-OH-MT after 12 and 24 weeks of therapy was higher in the group of patients who responded to therapy. 7-OH-MT appears to be a more persistent metabolite of MT and therefore more applicable for therapeutic drug monitoring of MT. The level of MT and its metabolites (MT monoglutamate, MTPG2 and 7-OH-MT) gradually decreases over time in responders to therapy. A 7-OH-MT concentration of 14.5 nmol/l may be a predictor of a good response to MT therapy.

Objective: to study the role of SAA1, CRP and STAT4 gene polymorphisms in the development of panniculitis (PN) and their relationship with clinical and laboratory parameters in the Russian cohort of patients.
Patients and methods. The study included 74 patients (67 women and 7 men aged 15 to 76 years) with diagnosis of PN. In addition to the general clinical examination, immunological and histological studies, computed tomography of the chest, and tuberculin tests were performed. For genetic study, two groups of patients were formed: with septal PN (SPN, n=26), represented by erythema nodosum (EN) and with lobular PN (LPN, n=48), including predominantly with idiopathic LPN (iLPN, n= 18) and other rare variants (n=30). As a control, the results of DNA genotyping of 142 healthy non-related individuals were used. Genotyping of polymorphisms rs12218 of the SAA1 gene, rs1205 of the CRP gene, and rs7574865 of the STAT4 gene was performed by the allele-specific real-time polymerase chain reaction.
Results and discussion. Significant differences were found between the groups in terms of age and duration of the disease. Patients with SPN were younger than those with LPN (p=0.013), had a shorter duration of the disease (p=0.001), and a lower ESR (p=0.001). Carriers of the TT genotype of the SAA1 gene polymorphism were twice as likely to develop LPN as compared to controls (odds ratio, OR 2.25; 95% confidence interval, CI 1.04–4.87; p=0.038), and this genotype was regarded as a risk factor. For patients with SPN, a significant risk factor was identified in the form of carriage of the mutant TT genotype of the CRP gene polymorphism. This genotype increased the predisposition to the development of EN by 4 times compared with the control (OR 4.39; 95% CI 1.26–14.11; p=0.009). There was a 6-fold increase in the risk of developing EN in carriers of the TT mutant genotype and the T allele of the STAT4 gene polymorphism compared with the control (OR 5.89; 95% CI 1.14–31.75; p=0.016 and OR 2.07; 95 % CI 0.99–4.19, p=0.030, respectively). Comparison of the frequencies of the T allele of the SAA1 gene polymorphism in the groups with EN and with iLPN revealed a higher frequency of the SAA1TT genotype and the SAA1T allele in iLPN than in EN (66.7 and 26.9%, p=0.066; 88.5 and 55.8 %, p=0.016, respectively).
Conclusion. The present study confirms the involvement of genetic factors, in addition to generally recognized environmental factors, in the pathogenesis of inflammatory diseases of adipose tissue. Polymorphisms of the SAA1, CRP, and STAT4 genes play a role in the formation of a genetic predisposition to the main clinical phenotypes of PN.

During the COVID-19 pandemic, many patients with rheumatic diseases were left without specialized care and information support, however, the current level of digitalization makes it possible to transfer the training and education of patients and their relatives to an online format.
Objective: to analyze the experience of holding a rheumatological school in an online format as a method of improving the medical literacy of the population.
Patients and methods. A cross-sectional study was performed by voluntary anonymous questioning of 157 patients who, from September 2020 to November 2021, took part in the online school on rheumatology held at the Clinical Rheumatology Center "New Hospital" (Yekaterinburg). All patients filled out an online questionnaire that included 15 questions related to age, place of residence, motivation of students, sources of information about the school, assessment of the form and content of lectures, quality and novelty of the information provided, and degree of doctor’s credibility.
Results and discussion. Analysis of the results of the survey demonstrated the interest of patients in obtaining high-quality medical information on rheumatology problems, a positive assessment of the format and content of the online school, its positive role in clarifying the essence of the disease and related problems.
Conclusion. Online schools for patients seem to be a relevant and promising area of medical prevention.

Juvenile idiopathic inflammatory myopathies (JIIM) are rare diseases in which the prognosis is largely determined by timely diagnosis, timing of prescription and effectiveness of therapy.
Objective: to characterize the clinical phenotypes, the results of paraclinical examination methods, the spectrum of autoantibodies, as well as therapeutic options in patients with JIIM.
Patients and methods. The retrospective study included 37 patients with JIIM hospitalized in the pediatric department of the V.A. Nasonova Research Institute of Rheumatology from 2016 to 2020. All patients underwent a standard clinical and laboratory-instrumental examination in accordance with the diagnosis and severity of the condition.
Results and discussion. Twenty-three of the 37 JIIM patients had juvenile dermatomyositis (JDM), 1 had polymyositis, and 13 had overlap-myositis (OM). The ratio of boys and girls was 1:1.7. The median age of onset for JDM was 6.9 years, and OM was 11.3 years. All patients had skeletal muscles involvement, dysphagia was detected in 52.2% of cases of JDM and in 15.4% of cases of OM. An increase in the level of creatine phosphokinase at the time of diagnosis was observed in 72.9% of patients, of lactate dehydrogenase – in 81.1%, of alanine aminotransferase - in 67.6%, of aspartate aminotransferase – in 75.7%. Heliotrope rash and/or Gottron's syndrome were observed in 100% of patients with JDM and in 30.8% with OM. Lung involvement was found in 27% of children. The myopathic capillaroscopic changes were present in 95.2% of patients with JDM and 53.8% with OM. Myositis-specific autoantibodies were found in 10.8% of patients with JIIM.
All patients received glucocorticoids, 81.0% methotrexate, 18.9% hydroxychloroquine, 8.1% cyclophosphamide, 8.1% cyclosporine, 2.7% mycophenolate mofetil, 2.7% azathioprine, 67.6% - intravenous immunoglobulin. Biologic disease modifying antirheumatic drugs (bDMARDs) were prescribed to 26% of patients with JDM and to all patients with OM (only in 51.3% of cases with JIIM). The median duration of illness before initiation of bDMARDs therapy was 2.25 years. 58.8% of patients were treated with rituximab (RTM), 41.2% with abatacept (ABA). In 1 patient with OM, represented by a combination of systemic lupus erythematosus and JDM, three bDMARDs were used sequentially: ABA, etanercept and RTM. All patients achieved inactive disease status.
Conclusion. JDM is the most common phenotype of JIIM, which is characterized by an earlier age of onset, skin involvement that precedes the development of myopathy, and typical capillaroscopic changes. The conclusion was made about the high efficacy and acceptable safety profile of bDMARDs therapy in children with JIIM, with careful monitoring of its tolerability. bDMARDs can be prescribed even in the early stages of the disease in the presence of unfavorable prognostic factors.

Patients' adherence to drug therapy, medical support and implementation of the doctor's recommendations for lifestyle changes can affect the effectiveness of therapy and quality of life in patients with rheumatoid arthritis (RA).
Objective: to analyze adherence to treatment, medical support and implementation of recommendations for changing the lifestyle in RA patients, including those with and without low-energy bone fractures.
Patients and methods. The study included 88 women with a definite diagnosis of RA. All patients were followed up for a long time (on average 8.45±1.34 years) at V.A. Nasonova Research Institute of Rheumatology. All patients underwent clinical, radiological and laboratory examinations, and a questionnaire for the quantitative assessment of adherence to treatment was completed.
Results and discussion. The integral indicator of adherence to treatment in 30 (34%) patients corresponded to a low level, in 51 (58%) – to an average level, and in 7 (8%) – to a high level. Low adherence to medical support was more often determined in patients with anxiety (p=0.02) and depression (p=0.04). The intake of oral glucocorticoids (GC) was associated with a high adherence to drug therapy (p=0.01). Adherence rates in the group of RA patients with and without bone fractures did not differ significantly. Functional disorders and the severity of radiological changes also did not differ significantly in patients with different levels of adherence.
Conclusion. Patients with RA had predominantly an average level of adherence to drug therapy, medical support, and a low level of adherence to recommendations for lifestyle changes. Oral GC were associated with high adherence to drug therapy, while low adherence to medical support was associated with anxiety and depression. Treatment adherence rates in the group of RA patients with and without bone fractures did not differ.

Objective: clinical and economic evaluation of the use of biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs), Janus kinase inhibitors (iJAK), for the treatment of ankylosing spondylitis (AS).
Patients and methods. Among comparison technologies for further analysis were included: adalimumab (ADA), golimumab (GLM), ixekizumab (IXE), secukinumab (SEC), tofacitinib (TOFA), certolizumab pegol (CZP), upadacitinib (UPA), etanercept (ETC). The efficacy and safety of the bDMARDs and tsDMARDs included in the study were evaluated based on the results of a systematic search and analysis of data on the comparative clinical efficacy and safety of their use. Any phase III randomized controlled trials of drugs used to treat active AS in adults (age ≥18) were considered as an investigational treatment versus placebo or versus another active drug. Analysis of the economic consequences of the use of bDMARDs and tsDMARDs for AS treatment was carried out only taking into account drug therapy. For the clinical and economic evaluation of the use of bDMARDs and tsDMARDs, the cost minimization indicator was calculated. As a criterion for clinical and economic efficiency and for the analysis of the impact on the budget, the cost per responder (CpR) indicator was estimated, which was calculated based on the cost of treating AS by the time the response was achieved according to the ASAS20/40 criteria and BASDAI50.
Results and discussion. The results of the meta-analysis indicated a greater effectiveness of bDMARDs and iJAK compared with placebo in terms of the frequency of achieving ASAS 20/40, BASDAI 50 criteria. From an economic point of view, compared with the reference (minimum) value (ETC biosimilar, Erelzi®), the difference in the treatment cost of 1 patient with AS during the year varied widely (from +4.22 to +40.29%) and depended on the selected therapy option. At the same time, UPA 15 mg was characterized by the lowest cost of a course of treatment in the first year among original drugs. Among the original drugs, the lowest CpR values before reaching the ASAS20 criterion were in ADA (380,986.58 rubles), ETC (426,868.81 rubles), GLM (559,619.28 rubles) and UPA 15 mg (582,003.89 rub.), according to the ASAS40 criterion – for ADA (534,518.49 rubles.), ETC (726,347.45 rubles) and UPA 15 mg (557,753.73 rubles), according to the BASDAI50 criterion – for ADA (488,911.11 rubles), ETC (636,386.99 rubles) and UPA 15 mg (640,204.28 rubles).
Conclusion. The study confirmed the clinical and economic feasibility of using various options for treatment of AS in real practice, including bDMARDs and iJAK. At the same time, the use of original drugs is not always associated with significant costs per 1 patient who responded to treatment. The creation of full-fledged patient registries will make it possible to introduce a system for monitoring clinical outcomes depending on the chosen treatment strategy, as well as smooth out the assumptions and limitations that are used in the study of the clinical and economic aspects of medical technologies, which will save resources and increase the availability of drugs for patients with rheumatic diseases.

Hypogammaglobulinemia is a condition caused by low levels of immunoglobulins in the blood serum. It can be a manifestation of primary immunodeficiency, characterized by a violation of the production of immunoglobulins, in particular common variable immunodeficiency (CVID). A typical clinical sign of CVID is various severe infections, among which infectious arthritis is not uncommon. At the same time, the clinical picture of infections can differ significantly from that in individuals with a normal immune response, including the spectrum of infectious arthritis pathogens.
The article describes a clinical case of an unusual course of infectious arthritis in a patient with newly diagnosed hypogammaglobulinemia. The peculiar features of the case were a long (more than 1.5 years) course of the disease, without the development of septic complications, no increase in ESR and CRP, recurrence of arthritis after a 2-month course of antibiotic therapy, and the presence of generalized edema. The causes and diagnosis, features of infectious complications, including infectious arthritis, and probable causes of edematous syndrome in CVID are discussed.

Systemic sclerosis (SSc) is a disease characterized by vasculopathy, fibrosis of the skin and internal organs, most often complicated by interstitial lung disease (ILD). The incidence of SSc reaches 20 cases per 1 million population per year, while changes in the lungs are found in more than half of patients and are characterized by a rapid increase in fibrosis, poorly controlled respiratory failure, and an unfavorable prognosis. It is important to trace the features of the formation and course of ILD and its relationship with occupational hazards in patients diagnosed with SSc. Dust pathology of the respiratory organs (chronic dust bronchitis and silicosis) is most typical for people with long work experience in mining. Silicosis in these patients may be accompanied by SSc with rapid progression of bronchial obstruction, restrictive disorders, as well as myocardial involvement and the development of pulmonary hypertension.

The article describes a clinical case of systemic lupus erythematosus (SLE) resistant to traditional treatment regimens and the first successful experience with the type I interferon inhibitor – anifrolumab, as part of an early access program in the Russian Federation. High efficacy and safety of the drug in the treatment of SLE with active lesions of the skin, mucous membranes and joints were noted.

Behcet's disease (BD) is a systemic vasculitis of unknown etiology, characterized by damage of vessels of any type and caliber, manifested by recurrent ulcerative process in the oral cavity and genital organs, eye damage, joints, gastrointestinal tract, central nervous system and other organs involvement. The pathogenesis of the disease is complex. The contribution of both innate and adaptive immune responses is noted. A feature of BD is hyperactivation of neutrophils and neutrophilic infiltration of affected tissues.
The review presents data from studies related to the assessment of the main functions of neutrophils in this disease.

The need for effective drugs for the treatment of knee osteoarthritis (OA) is constantly growing. Current guidelines recommend the use of symptomatic slow acting drugs for osteoarthritis (SYSADOA) such as glucosamine (GCA) in this disease. Among various drugs containing GCA, high bioavailability and clinical efficacy have been shown only for prescription crystalline GCA sulfate (pGCAS) administration. Several meta-analyses and network meta-analyses have shown that efficacy of pGCAS 1500 mg once daily is superior to other GCA-based products (such as GCA hydrochloride with or without sodium sulfate) and the combination of GCA with chondroitin sulfate (CS) in terms of reducing the intensity of pain and improving the functional state. These studies confirmed the favorable safety profile of pGCAS, which was comparable to placebo in the incidence of adverse events. Pharmacoeconomic studies have also demonstrated greater cost-effectiveness of pGCAS compared to other GCA drugs.
A group of Russian experts at a meeting of the advisory committee reviewed the evidence in favor of the use of pGCAS and evidence of its effectiveness in the treatment of knee OA in comparison with other products that include GCA, and the fixed combination of GCA with CS. Taking into account the results obtained, the use of pGCAS at a dose of 1500 mg once a day is recommended as a rational choice for the treatment of knee OA.

Chronic non-specific back pain (CNBP) is the most common pathology of the musculoskeletal system, affecting from 10 to 60% of the adult population in the world, causing severe suffering, disability and a significant deterioration in the quality of life. Osteoarthritis (OA) should be considered as one of the main reasons of the development of CNBP – inflammatory and degenerative changes in the facet and sacroiliac joints, as well as the spinal column itself (in particular, osteitis of the Modic 1 type). Spinal OA is accompanied by biomechanical disturbances, nociplastic (peripheral and central sensitization) and psycho-emotional changes that form a complete picture and various CNBP phenotypes.
Recognizing the leading role of OA as the cause of CNBP, it is advisable to use the same therapeutic approaches in this syndrome as in OA of peripheral joints. In particular, it is necessary to consider the use of symptomatic slow acting drugs for osteoarthritis (SYSADOA) in CNBP as the main pathogenetic therapy.
Alflutop is one of the most popular parenteral SYSADOA widely used in Russian practice. This drug has a good evidence base: this review presents data from 12 clinical trials of Alflutop in CNBP (n=1479), which confirmed its efficacy and safety.

The article presents an analysis of the therapeutic effect of the drug diacerein (D), which has been used in osteoarthritis (OA) for more than 20 years and is included in the clinical guidelines of the Association of Rheumatologists of Russia (2021) and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal diseases (ESCEO, 2019) for the treatment of OA. The main pathogenic effect of D in OA is to suppress the synthesis of interleukin 1, stimulate the production of articular cartilage proteoglycans, and slow down abnormal remodeling of the subchondral bone. The advantages of D in the treatment of patients with OA and comorbidities are presented – a prolonged anti-inflammatory and analgesic effect and good tolerability. These properties of D allow to control the symptoms of OA and improve the quality of life of patients. The structure-modifying effect of D is based on its ability to stimulate the synthesis of articular cartilage proteoglycans with long-term use and prevent abnormal remodeling of the subchondral bone, which leads to a decrease in the risk of OA progression and a delay in total joint arthroplasty. An important advantage of D is its positive metabolic effect in patients with type 2 diabetes mellitus and obesity, which is associated with the ability of D to reduce the level of glycated hemoglobin and body mass index. Data are presented on the absence of adverse cardiovascular effects when using D, which allows us to recommend its use in patients with OA who have comorbid cardiovascular diseases, as well as contraindications for non-steroidal anti-inflammatory drugs.

Osteoporosis (OP) occupies one of the leading places in the structure of morbidity in people over 50 years of age, and its social significance is associated with the main complications – low-energy fractures of the vertebral bodies and bones of the peripheral skeleton, which lead to an increase in disability and mortality among the elderly, being a serious problem for public health. One of the doctor’s goals is the timely administration of anti-osteoporotic treatment. Bisphosphonates (BP) are first-line drugs for the treatment of OP. Since 1995, nitrogen-containing BPs have been widely used, they demonstrate their effect primarily by inhibiting the activity of osteoclasts and stimulating their apoptosis. The efficacy and safety of this class of drugs have been confirmed by numerous studies and many years of clinical practice. Since 2005, the production of generics of alendronic acid began, and later, after the patent protection of other BFs was closed, generics of risedronic, ibandronic and zoledronic acids appeared. In 2019, two domestic generics were registered – ibandronic acid 3 mg for intravenous (IV) injection once every 3 months (Rezoviva) and zoledronic acid 5 mg in 100 ml solution for IV injection once a year (Osteostatics). Since 2020 they have been introduced into clinical practice as part of import substitution, which increased the availability of these drugs and reduced the health care costs.

Standardized extracts of undenatured type II collagen (UC-II) are used as alternative approaches to the treatment of osteoarthritis (OA). The effect of UC-II extracts is associated with the modulation of the mechanisms of innate and acquired immunity, a decrease in the activity of proinflammatory cytokines and prostaglandins. Epitopes of native collagen in the structure of UC-II contribute to a decrease in the activity of autoimmune reactions that stimulate cartilage degradation. Interacting with discoidin receptors, UC-II accelerates the reconstruction of cartilage connective tissue and inhibits the pro-inflammatory effects of endogenous collagens. Experimental and clinical studies confirm the effectiveness of the use of standardized substances UC-II for acceleration of cartilage regeneration and reduce pain in OA and subclinical joint dysfunction.

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used type of drugs in the world and are prescribed for a wide range of indications, including osteoarthritis, rheumatoid arthritis, other diseases of the musculoskeletal system and soft tissues, as well as for the relief of postoperative pain. It is well known that the use of NSAIDs is associated with the risk of gastrointestinal (GIT), cardiovascular (CVS) and kidneys complications. Lornoxicam belongs to the NSAIDs of the oxicam class and is a balanced inhibitor of both cyclooxygenase (COX) isoforms – COX1 and COX2 – and differs from other oxicams in its rapid onset of action, high elimination rate. The drug is characterized by a pronounced analgesic effect and a favorable safety profile both in relation to the gastrointestinal tract and cardiovascular system, does not require dose adjustment in patients over 65 years of age.