Glucagon-like peptide-1 receptor agonists (ArGLP-1) are effective drugs for the treatment of type 2 diabetes mellitus and obesity. Recent studies in patients with a wide range of immunoinflammatory diseases suggest important pleiotropic mechanisms of action of these drugs, primarily related to the suppression of inflammation. The article presents new data indicating the prospects for the use of ArGLP-1 in immunoinflammatory rheumatic diseases, which dictates the need for clinical studies. GLP-1 receptor agonists are effective drugs for the treatment of type 2 diabetes mellitus and obesity. Recent studies in patients with a wide range of immune-mediated diseases suggest important pleiotropic mechanisms of action of these drugs, primarily related to the suppression of inflammation. The article presents new data indicating the prospects for the use of ArGLP-1 in immune-mediated rheumatic diseases, which dictates the need for clinical studies.

Glucocorticoids (GC) have been used in medicine since the middle of the twentieth century, including for the treatment of various systemic rheumatic diseases. However, long-term use of GC may be accompanied by the development of serious complications, one of which is secondary osteoporosis, leading to low-energy fractures, which affects the quality of life of patients and may lead to an increased risk of death. This article presents an overview with a discussion of the new edition of the guideline of the American College of Rheumatology (ACR) 2022 for the prevention and treatment of glucocorticoid-induced osteoporosis in adult patients.

Modern pathogenetic therapy of inflammatory rheumatic diseases (IRD) is aimed not only at reducing disease activity (although achieving remission and low disease activity remains the main goal of treatment), but also at eliminating as quickly and completely as possible the main symptoms that cause a decrease in the quality of life of patients. Particular importance is attached to effective control of chronic pain – the main and most distressing manifestation of IRD. To solve this problem, the pathogenesis of chronic pain in IRD continues to be actively studied, aimed at finding new ”targets” of pharmacotherapy. Thus, the role of central sensitization (CS) and comorbid fibromyalgia in the formation of clinical manifestations of IRD is now clearly proven. Signs of CS, depending on the instrument of its detection, are determined in 20–40% of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA).

Interleukin (IL) 17 plays a fundamental role in the development of chronic pain in IIRD. This cytokine takes a leading position in the development of the ”cytokine cascade”, inducing the synthesis of various cytokines and chemokines, as well as chemotaxis and activation of neutrophils and T cells. Induction of synthesis of inflammatory mediators (including prostaglandin E2) determines the role of IL-17 in activation of nociceptors and their sensitization. IL-17 also takes an active part in neuroimmune interactions by activating glia cells and affecting receptors present on the membrane of neurons of the posterior horns of the spinal cord. This defines the role of IL-17 as one of the inductors of CS development. Pharmacologic blockade of IL-17 is a known pathway to suppress the activity of IIRPs such as PsA and AxSpA. However, this mechanism also allows for significant effects on chronic pain. In particular, the IL-17 inhibitor ixekizumab has shown high analgesic potential in a series of studies in PsA and AxSpA (SPIRIT-P1 and SPIRIT-P2, COAST V and COAST W). It is important to note that this drug demonstrated a very rapid analgesic effect: pain intensity was significantly reduced already 7 days after the first injection. These data suggest a specific effect of ixekizumab on the nociceptive system, independent of the anti-inflammatory effect. This fact allows us to consider ixekizumab as a drug of choice for the treatment of patients with PsA and AxSpA who experience severe pain and have signs of CS and fibromyalgia.

The prevalence of hyperuricemia (HU), which can be considered the first stage of gout formation, varies in different countries and tends to increase. Uric acid (UA), even in its dissolved form, activates damage and potentiates the death of articular cartilage cells through direct cytotoxicity and a number of other pathogenetic mechanisms. The possible association of HU and osteoarthritis may be due to a number of common pathogenetic mechanisms, but the direction of this relationship is still a debatable issue. The accumulated data suggest the need for a deeper study of the relationship between gout and HU with pathological processes leading to the development and progression of osteoarthritis and bone metabolism disorders.

Objective – to compare clinical characteristics of patients with axial spondyloarthritis (axSpA)/ankylosing spondylitis (AS) and with axial psoriatic arthritis (axPsA).

Subjects and methods. 100 patients were examined: 45 – with axSpA/AS (group 1), 55 – with axPsA (group 2). Patients of group 1 were included according to axSpA/AS criteria, patients of group 2 – according to CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria, and having axial involvement (axPsA). Axial involvement was detected in case of radiologically significant sacroiliitis (bilateral grade ≥2 or unilateral grade ≥3) or active MRI sacroiliitis, or ≥1 syndesmophyte(s) of the cervical and/or lumbar spine. Patients were evaluated for presence of inflammatory back pain (IBP) by ASAS (Assessment of Spondyloarthritis International Society) criteria.

Results and discussion. Patients of group 1 were younger (p<0.001), more often HLA-B27 positive (p<0.001), had more IBP (p=0.001). Patients of group 2 had older age (>40 years) at back pain onset (p<0.001), more often peripheral arthritis (p<0.001), dactylitis (p=0.004), and skin psoriasis (p<0.001). Nail psoriasis was found only in group 2 patients (p<0.001). Group 1 patients had more often heel enthesitis (p=0.005). Group 2 patients had worse axial disease activity scores: BASDAI (Bath Ankylosing Spondylitis Disease Activity Index; p=0.006) and ASDAS-СRP (Ankylosing Spondylitis Disease Activity Score with C-reactive protein level determination; р<0.001); and worse patient reported outcomes: BASFI (Bath Ankylosing Spondylitis Functional Index; p=0.004), patients’ pain (p=0.005) and patients’ global assessments (p=0.036). Patients of group 2 had more syndesmophytes of the lumbar (р=0.009) and cervical (р=0.007) spine. Only in group 2 patients, chunky “non-marginal” syndesmophytes were found (in 32.1%), as well as spinal lesions without sacroiliitis (in 20.0%). Patients of group 2 had more joint erosions (р=0.001), osteolysis (р=0.015), juxta-articular bone formation (р<0.001) and joint ankyloses (р=0.02). All patients of group 1 and only 80% of group 2 (р=0.003) met ASAS criteria for axSpA. AxSpA/AS and axPsA seem to be two different diseases. In our cohort of patients, axPsA patients had worse disease status compared to axSp and AS.

The aim of this work is to clarify the association between the clinical and psychopathological features of mental disorders (MD) and the clinical and immunological features of antiphospholipid syndrome (APS).

Material and methods. The study included 107 patients (34 (31.8%) men and 73 (68.2%) women) aged 18 to 69 years (40.6±10.4 years (M±SD)), 54 (50.5%) – with primary APS (PAPS), established according to the international criteria of 2006 and 53 (49.5%) patients – with reliable diagnosis of systemic lupus erythematosus (SLE), according to the European Alliance of Associations for Rheumatology/American College of Rheumatology (EULAR/ ACR) 2019 criteria, with a secondary APS. Risk of thrombosis in APS was assessed by the GAPSS (Global Anti-Phospholipid Syndrome Score). MD were diagnosed by a psychiatrist in accordance with 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) and Diagnostic and Statistical Manual of mental disorders, 5th edition (DSM-5).

Results. Mental disorders are detected in the vast majority of patients with APS (98 (91.6%)), predominantly in anxiety-depressive spectrum disorders (ADSD; 90 (84.1%)). Depressive disorders are not associated with a high risk of thrombosis according to the GAPSS, but more severe variants of depression are more common in patients with high anti-β2 -glycoprotein I (anti-β2 GP1) and low/moderate anti cardiolipin (aCL) antibodies. Anxiety disorders were diagnosed only in patients with a high risk of thrombosis according to GAPSS, high aCL and IgG anti-β2 GP1. Schizotypal disorder was identified only in patients with a high risk of thrombosis and positive anti-phosphatidylserine/prothrombin complex antibodies (aPS/PT) regardless of class, and also more often in patients with high IgG anti-β2 GP1. Epilepsy was observed only in patients with positive aPS/PT, regardless of class. Cognitive impairment (CI), mostly mild and moderate, was found in the vast majority of patients with APS (102 (95.3%)). Dementia was detected in 7 (6.5%) patients, and only in those who had acute or transient cerebrovascular accident. When compared with the general population, dementia developed at an earlier age (up to 65 years). For patients with a high risk of thrombosis, moderate CI is more typical. CI and their severity are not associated with the duration of APS, but are associated with positivity for IgG aPS/PT, acute or transient cerebrovascular accident and the duration of comorbid ADSD.

Conclusion. A high frequency of MD in patients with APS revealed. Associations of MD with clinical and immunological manifestations of APS were determined. CI in patients with APS is heterogeneous and are associated with both clinical and immunological manifestations of APS and MD. Identification of CI and determination of their characteristics should be confirmed by clinical, psychopathological and pathopsychological methods in order to personalize their correction within the partnership model of care.

The aim of the study was to investigate the relationship between cytokine levels and values of antibodies to cyclic citrullinated peptide (anti-CCP) and antibodies to carbamylated proteins (anti-CarP) in patients with rheumatoid arthritis (RA). Materials and methods. 106 patients with a reliable diagnosis of rheumatoid arthritis were included in the study. Determination of anti-CarP and anti-CCP was performed by enzyme immunoassay. Patients were divided into subgroups depending on the values of anti-CCP and anti-CarP. The concentration of 27 cytokines in serum was determined using multiplex xMAR technology. Results and discussion. When comparing immunological subgroups, anti-CCP(+) patients had higher concentrations of interleukin (IL) 1β, IL-1Ra, IL-2, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, fibroblast growth factor, granulocyte colony-stimulating factor (CSF), granulocyte-macrophage CSF, interferon (IFN) γ, IFN0γ-induced protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1α (MIP-1α), transforming growth factor bb, tumor necrosis factor α and vascular endothelial growth factor. IL-5, IL-9, eotaxin, MIP-1β and RANTES (regulated on activation, normal T cell expressed and secreted) values were higher in anti-CCP(–) patients. In the subgroup of anti-CCP(–) patients, an inverse correlation was found between IL-5 and total Sharpe score, between IL-9 and DAS28-CRP (Disease Activity Score with C-reactive protein calculation). In anti-Carp(–) patients (n=73) higher values of IL-17 were recorded. Conclusion. Our data support the concept of RA heterogeneity, characterised by the existence of different clinical and immunological subtypes, which may have implications for improving personalised therapy.

Currently, methotrexate (MT) remains one of the immunosuppressive drugs most commonly used in rheumatology. However, its effect on the immunogenicity of vaccines has until recently been studied only to a limited extent, which has led to the lack of clear recommendations for the use of MT during vaccination. Significant progress was made during the COVID-19 pandemic due to the dynamic development of vaccine research, including in patients with immuno-inflammatory rheumatic diseases. The review presents data on the effect of MT on the immunogenicity of vaccines against influenza, pneumococcus, herpes zoster, tetanus/diphtheria/pertussis, yellow fever and COVID-19 (including humoral and cellular responses) in rheumatological patients. The necessity of observing certain time intervals during vaccination in the case of MT use has been demonstrated. The potential mechanisms by which MT influences the immunogenicity of vaccines are presented. The importance of further clinical studies is emphasized in order to assess the effect of MT therapy on the vaccine response and to develop methods for its optimization.

Introduction. Cutaneous Lupus Disease Area and Severity Index (CLASI) and its modified version, the Revised Cutaneous Lupus Erythematosus Disease Areas and Severity Index (R-CLASI) are tools for quantifying skin and mucosal lesions in patients with both cutaneous lupus erythematosus and its systemic variant. Evaluation of the scales of activity and skin damage in systemic lupus erythematosus (SLE) is associated with the need to stratify their quantitative characteristics. The Cutaneous Lupus Disease Area and Severity Index (CLASI) and its modified version the Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (R-CLASI) are a tool for quantifying skin and mucosal lesions in patients with both cutaneous lupus erythematosus (CLE) and its system version.

Objective. To validate the indexes of objective assessment of skin activity and damage CLASI and R-CLASI in the Russian cohort of patients with systemic lupus erythematosus and compare it with dermatological assessments of the quality of life.

Material and methods. The study included 55 patients with SLE with various types of skin and mucosal lesions, the median age was 30.0 [26.0; 40.0] years, the duration of the disease was 7.0 [3.0; 14.0] years. To assess the active (reversible) lesion and irreversible skin damage, the CLASI and R-CLASI indexes were used, for the general assessment of activity and damage in SLE, the SLEDAI-2K and SLICC/ACR DI were used.

Results. The most common variant of skin lesions in patients with SLE is acute cutaneous lupus erythematosus (ACLE) – 45%, as well as alopecia, which occurs in 62% of cases. The median activity index for CLASI was 5.0 [2.0; 11.0], and R-CLASI was 7.0 [3.0; 18.0]; the median damage index for CLASI was 5.0 [2.0; 11.0], and R-CLASI was 2.0 [0.0; 7.0]. A significant relationship was revealed between the medians of CLASI and R-CLASI scores depending on the degree of activity according to SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index) and the damage Index (DI) in SLE (SLICC/ACR DI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) when recalculating these indexes only for skin and mucous lesions. According to the ROC analysis, the CLASI and R-CLASI skin activity and damage indices showed high sensitivity (CLASI activity index – 98%, R-CLASI – 93%, CLASI and R-CLASI damage index – 91%) and specificity (CLASI activity index – 64%, R-CLASI – 71%, CLASI and R-CLASI damage index – 86%).

Conclusion. To assess the severity of skin and mucosal lesions in patients with SLE in the Russian Federation, it is reasonable to use the CLASI and R-CLASI indices. The CLASI and R-CLASI indices reflect the level of activity and severity of skin lesions, with higher values of these indices indicating more severe skin lesions and a significant impact on the overall well-being of SLE patients. Patients with high values of these indices often experience feelings of embarrassment, discomfort, difficulty in performing daily tasks, and limitations in social life. To assess the severity of skin and mucous lesions in patients with SLE in the Russian Federation, it is advisable to use the CLASI and R-CLASI indexes.

Monogenic familial autoinflammatory Behçet-like syndrome/haploinsufficiency A20 syndrome is a hereditary autoinflammatory disease from the group of ubiquitinopathies which are caused by a mutation of the TNFAIP3 gene encoding the A20 protein with an autosomal dominant inheritance mechanism and clinical picture similar to Behçet’s disease. Pathogenesis is based on a 50% function decreasing of the nuclear factor inhibitor protein NFkB, what leads to overexpression of proinflammatory cytokines. The disease onset is usually in childhood. Clinical features are presented with recurrent aphthous stomatitis and genital aphthae in most patients and also inflammatory bowel damage is noted. Eye damage is noted rarely than in sporadic Behçet’s disease. In addition, the clinical picture may be presented with arthritis, skin rashes, lesions of the cardiovascular system (pericarditis), fever. Increasing of acute-phase markers is noticed, there is a high frequency of autoantibodies detection in contrast with “classic” autoinflammattory diseases. It can be combined with other autoimmune diseases (systemic lupus erythematosus (SLE), autoimmune thyroiditis, hepatitis, etc.). The description of two patients and comparison with another patient from Russia who was described earlier are presented. All patients had aphthous stomatitis and genital aphthaes, intestinal inflammation symptoms, which was dominanting in one of the patients. Another patient had severe polyarthritis in combination with immunological manifestations which were typical for SLE. The first patient had a good clinical response with the tumor necrosis factor inhibitor adalimumab, the second patient – the anti-B cell drug rituximab.

Total joint replacement (TJR) is a surgical procedure widely used in severe destructive joint damage. TJR of the knee and hip joint (TKR and THR respectively) occupies an important place in the complex treatment of rheumatoid arthritis (RA) and osteoarthritis (OA), and can significantly reduce pain and improve function in patients with severe structural joint damage due to an ineffectiveness of conservative therapy. In recent years, due to the development of the modern concept of active treatment of RA (treat-to-target) and the introduction of new classes of anti-inflammatory drugs, such as biologic disease modifying antirheumatic drugs and JAK inhibitors, the need for TJR in RA has begun to decrease. At the same time, the aging of the population, the increase in the number of patients with OA and the lack of generally approved pathogenetic therapy determine the increase of TKR/THR incidence in this disease. This review presents the long-term dynamics of the incidence of TKR and THR according to the national registers of different countries. The issues of the complication risks in patients with RA and OA, current recommendations for anti-rheumatic therapy in RA in the perioperative period are also considered.

Relapsing polychondritis (RPC) is an autoimmune disease manifested by both repeated attacks and a persistent inflammatory process with progressive destruction of cartilaginous structures, in particular, chondritis of the ears, nose, larynx, bronchi, and joints. RPC is a rare disease (about 1000 cases have been described worldwide). Diagnosis of RPC and the choice of treatment tactics are very difficult, which is associated with the rarity of the pathology, undulating, unpredictable course, and the lack of specific laboratory markers.

The clinical observations presented in the article confirm the complexity of diagnosing RPC. Before the disease was verified, both patients repeatedly consulted different specialists: the first patient was diagnosed 3 months after the onset of characteristic symptoms of RPC, and the second patient – 1.5 years later. Late diagnosis and the lack of a unified approach to treatment were the reason for the development of prognostically unfavorable lesions in the second patient – chondritis and perichondritis of the larynx.