The paper is devoted to modern ideas about the role of immune-inflammatory mechanisms in the development of resistant schizophrenia. The significance of autoimmune reactions is discussed. Promising targets of therapeutic strategies are considered.

Systemic autoimmune rheumatic diseases (SARD) are clinical and immunological syndromes characterized by the development of both unique and common (partially overlapping) clinical and pathological manifestations, a variety of course and progression options, “response” to anti-inflammatory therapy and the severity of “comorbid” pathology. Intravenous immunoglobulin (IVIG) has held a prominent position in the spectrum of drugs used to treat SARD for over 50 years. Another equally important indication for its use is replacement therapy for primary (inborn errors of immunity) and secondary immunodeficiencies. In fact, IVIG is a prototype of “biological agents”, preceding the development of monoclonal antibodies (mAbs), which began to be used in clinical practice for the treatment of SARDs. This narrative review examines new data regarding the efficacy and safety of IVIG in SARDs and the role of IVIG in replacement therapy in patients with hypogammaglobulinemia, primarily associated with anti-B cell therapy. Draft clinical guidelines regarding the use of IVIG for the treatment of SARDs are presented.

The article presents an updated version of the recommendations on the use of antirheumatic drugs in reproduction, pregnancy and lactation developed by the European Alliance of Rheumatology Associations in 2024 and commenting on them.

Most patients with systemic lupus erythematosus (SLE) present with some form of skin involvement. Skin manifestations of lupus are classified as lupus-specific or lupus-nonspecific based on histopathologic findings. Lupus-specific skin lesions include chronic cutaneous lupus erythematosus, subacute cutaneous lupus erythematosus, and acute cutaneous lupus erythematosus. Nonspecific and rare SLE skin lesions are more common in patients with high disease activity and in some cases may be considered a sign of another pathological process, including other connective tissue diseases. It is important for the rheumatologist to be familiar not only with the spectrum of typical SLE skin manifestations but also with the rare, nonspecific lesions to help predict the likelihood of systemic disease and provide patients with timely therapy to control disease activity and prevent damage.

The aim – to identify clinical characteristics of resistant to therapy psoriatic arthritis (PsA) patients.

Material and methods. 459 patients (M/F=213/246), mean age 46.1±12.5 years (yrs) with PsA treated by biologic or target synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) within 2 yrs were included. Difficultto-treat (D2T) PsA was defined as failure of ≥2 b/tsDMARDs with different mechanism of action among tumor necrosis factor (TNF) inhibitors, anti-interleukin (IL) 17, anti-IL12/23, anti-IL13 and Janus kinase (JAK) inhibitors within 2 yrs of follow-up. Complex-to-manage (C2M) PsA was defined as failure of ≥2 b/tsDMARDs and includes additional factors such as lack of access to treatment or contraindication or intolerance. D2T and C2M patient’s characteristics were compared with each other and with responders to therapy (non-D2T) patients using statistical tests.

Results. 352 (76.7%) patients (M/F=163/189) responded to the first b/tsDMARDs. 107 (23.3%) patients were resistant to treatment. Of these, 53 (11.5% of all those included in the study) (M/F=26/27) were identified as D2T and 54 (11.8%) (M/F=24/30) as C2M. A comparative analysis performed of 107 resistant and 352 responding patients with PsA showed that PsA-resistant patients had a significantly more often enthesitis 31% vs 17% (p=0.002), dactylitis 34% vs 20% (p=0.004), depression 30% vs 19% (p=0.002), cardiovascular diseases 28% vs 40% (р=0.031) and ≥2 comorbidities 39% vs 51% (р=0.045), than those who responded to treatment. A comparative analysis performed of 54 C2M PsA and 53 D2T PsA showed that C2M patients had a significantly more often pain/discomfort 43% vs 19% (p=0.024) and depression 41% vs 19% (p=0.04), significantly less often enthesitis 15% vs 47% (p=0.001) and dactylitis 24% vs 43% (р=0.04) than D2T PsA.

Conclusions. In real clinical practice treatment-resistant PsA patients occur in quarter (23.3%) cases, of them D2T PsA patients – in 11.5% and C2M – in 11.8% cases. Treatment-resistant PsA patients compared with responders to therapy are characterized by presence of enthesitis, dactylitis and various comorbidities mainly depression and cardiovascular disease. C2M PsA patients compared with D2T PsA are characterized by presence of pain/discomfort and depression.

Systemic lupus erythematosus (SLE) is a chronic autoimmune rheumatic disease associated with a high risk of cardiovascular disease (CVD). Modern studies show that patients with SLE are susceptible to early development of atherosclerosis, which increases the risk of heart attacks and strokes even in young patients. An early predictor of cardiovascular disease (CVD) is arterial stiffness (AS), the assessment of which using such parameters as pulse wave velocity (PWV) and augmentation index (AIx) makes it possible to detect reduced elasticity of the vascular walls. However, the mechanisms of its development in these patients have not been fully studied, and the diagnostic and prognostic values require further study. Thus, the study of arterial stiffness in patients with SLE is of significant scientific and clinical interest.

The aim – to study the parameters of local arterial stiffness in patients with systemic lupus erythematosus and their relationship with traditional risk factors, the QRISK-3 cardiovascular risk score and clinical and immunological indicators Materials and methods. The study included 114 patients with SLE and 35 ageand sex-matched control participants. Women predominated in the SLE group (88%), with a mean age of 37±11 years. The most common clinical manifestations of SLE at the time of enrollment were joint involvement – in 67 (59%) patients, skin involvement – in 36 (31%), and hematologic disorders – in 34 (30%). A positive ANA was detected in 100% of cases, elevated anti-dsDNA levels in 80 (70%) patients, and hypocomplementemia in 76 (67%). Glucocorticoid therapy was received by 91 (80%) patients, hydroxychloroquine – by 80 (70%) and other cytostatic drugs – by 39 (34%) at the time of inclusion in the study. All participants underwent ultrasound of the common carotid arteries with a study of the AIx and pulse wave velocity (PWV) in the supine position. Before the ultrasound, all patients underwent physical, instrumental and laboratory examinations, the presence of traditional risk factors (TRF) was assessed, and the risk of developing CVD was calculated using the QRISK-3 scale.

Results. In patients with SLE, higher AS values were found compared to the control group: AIx on the left – 1.9 [–0.2; 5.3] vs 0.0 [–1.1; 2.1]%; AIx on the right – 1.1 [–0.1; 5.1] vs 0.1 [–0.6; 2.3]%; PWV on the left – 7.2 [6.1; 8.4] vs 6.6 [5.8; 7.6] m/s, respectively (p<0.05 in all cases). A relationship was found between AR and TRF – age, arterial hypertension and dyslipidemia, QRISK-3. In patients with SLE who have atherosclerotic plaques (AP), vascular stiffness is higher compared to patients without AP. A correlation was found between PWV and AIx with immunological parameters (antiβ2-GP1, anti Ro/SS-A), intima-media thickness, and QRISK-3.

Conclusions. The obtained results emphasize the multifactorial mechanism of vascular changes in SLE, including TGF, SLE-related factors. These data can serve as a basis for more accurate risk stratification and personalized selection of therapy in patients with SLE.

The development of cardiovascular disorders associated with atherosclerotic vascular lesions is a common complication of autoimmune rheumatic diseases (AIRDs), leading to a life expectancy decrease. Rheumatoid arthritis (RA) has a special place among the AIRDs, and the incidence of atherosclerotic vascular disease is 1.5-fold higher than in the general population, which is comparable to type 2 diabetes mellitus. This difference is due to the shared immunopathogenetic mechanisms of RA and atherosclerosis.

The aim of the study was to identify predictors of cardiovascular adverse events (CAE) during therapy with the interleukin 6 (IL-6) inhibitor olokizumab (OKZ) and to evaluate the cardioprotective potential of this monoclonal antibody.

In a pooled retrospective analysis of data from randomized and open-label, long-term clinical trials of the OKZ efficacy in patients with RA, we evaluated the effects of OKZ therapy on the incidence of CAE and the following lipid profile parameters: apolipoprotein B (ApoB), apolipoprotein A1 (ApoA1), lipoprotein-a (Lp(a)), adiponectin, homocysteine, and albumin.

During treatment with OKZ, an increased risk of CAE was independently associated with age over 60 years (hazard ratio (HR) – 1.59; 95% confidence interval (95% CI): 1.12–2.26), elevated (>30) body mass index (HR=1.75; 95% CI: 1.26–2.45), hypertention (HR=2.44; 95% CI: 1.46–4.06) and ApoA1 (>2.25 g/L) (OR=2.23; 95% CI: 1.05–4.72). During treatment with OKZ, an increase in adiponectin levels, a decrease in homocysteine, Lp(a), and no changes of the ApoB/ApoA1 ratio were noted. Favorable dynamics of cardiovascular risk biomarkers in patients receiving active therapy compared to placebo indicate a likely positive effect of OKZ on the cardiovascular system.

Divozilimab (DIV) is a new monoclonal antibody drug against CD20, which has demonstrated efficacy and safety in patients with systemic sclerosis (SS) in terms of reducing skin fibrosis and stabilizing lung function.

The aim of the study was to assess the dynamics of skin fibrosis according to the mRSS in SSD patients treated DIV with depending on gender, disease duration and initial lung function.

Material and methods. A post hoc analysis of data from a 48-week randomized placebo-controlled phase III clinical trial BCD-132-5/LIBERIUS was conducted. 151 patients with SS were randomized into groups treated with DIV (n=76) or Placebo (n=75). DIV was administered intravenously at 250 mg on weeks 0 and 2, and then at 500 mg once every 24 weeks. The efficacy of DIV compared to placebo in terms of reducing skin fibrosis according to the mRSS was evaluated in subgroups of patients formed by gender (female/male), disease duration at the time of therapy initiation (less than 3 years, from 3 to 5 years, and more than 5 years), as well as by initial lung function (forced vital capacity (FVC) % predicted ≥80%/<80%).

Results. The average change in mRSS from baseline at week 48 in men was –6.1±2.1 in the DIV and 1.6±6.2 in Placebo (LS mean difference (LSMD) –7.5 (95% CI: –11.6; –3.4); p=0.0004). In the subgroup of women, the change in mRSS was –5.1±4.1 and –2.5±4.4 in the DIV and Placebo groups respectively (LSMD=–2.5 (95% CI: –4.0; –1.0); p=0.001).

In patients with a SS duration of up to 3 years, the mRSS dynamics was the most pronounced: –5.6±4.0 in DIV compared to –0.7±6.0 in placebo (LSMD=–5.2 (95% CI: –7.4; –2.9); p<0.0001). In the other subgroups, mRSS dynamics were numerically higher under DIV treatment compared to placebo: –5.2±3.5 and –2.2±2.9 (LSMD=–2.6 (95% CI: –5.5; 0.3); p=0.078) in the subgroup with SS duration of 3 to 5 years and –5.0±4.2 and –3.4±3.8 (LSMD=–1.2 (95% CI: –3.5; 1.0); p=0.285) in patients with a disease duration of more than 5 years.

DIV demonstrated a significant effect in the subgroup with initially normal lung function, where mRSS dynamics was –5.4±3.5 in DIV and –2.4±4.2 in placebo (LSMD=–2.8 (95% CI: –4.4; –1.2), p=0.0008), as well as in patients with initial FVC<80% of predicted, where mRSS reduction was –4.9±4.6 and –0.1±7.0 in DIV and in placebo respectively (LSMD=–5.5 (95% CI: –8.6; –2.4); p=0.0006).

A statistically significant difference in mRSS dynamics was found between male and female subgroups (p=0.024) and a trend toward higher efficacy in patients with disease duration of less than 3 years compared to subgroups with a SS duration of 3 to 5 years and more than 5 years (p=0.056). No differences in DIV efficacy were found between subgroups of patients with initially normal and reduced lung function (p=0.133).

Conclusion. DIV is a promising and effective therapeutic option for all patients with SS, regardless of gender, although a more pronounced effect on reducing skin fibrosis can be expected in men. DIV therapy is appropriate at any SS duration, but the highest efficacy in terms of skin fibrosis is observed in patients with recently developed disease. A significant and marked reduction in skin score in patients with initially normal and reduced lung function defines the possibility of DIV therapy in a broad population of SS patients. This is promising for improving the visceral lesions prognosis during DIV therapy, especially in the case of early therapy.

Takayasu arteritis is a rare large vessel vasculitis affecting the aorta, its branches and the pulmonary artery. With a progressive course, the disease can lead to the development of stroke, ischemia of the upper extremities and a decrease in quality of life. There is a limited number of long-term results of treatment of Takayasu arteritis and there are no studies on assessing the quality of life in patients after surgery.

The aim of the study was to study the quality of life of patients with Takayasu arteritis who underwent surgery for damage to the branches of the aortic arch.

Materials and methods. The quality of life in the long-term period was assessed in 21 patients with Takayasu arteritis. They operated in the department of vascular surgery of A.V. Vishnevsky National Medical Research Center of Surgery from January 2001 to December 2021. Quality of life was assessed using the SF-36 (Short Form 36) questionnaire, Hospital Anxiety and Depression Scale (HADS), the Morisky – Green compliance scale and a specialized questionnaire developed as part of this study.

Results and discussion. When assessing the level of anxiety and depression on the HADS, it was revealed that 42,8% of operated patients with Takayasu arteritis have disorders in the psychoemotional sphere. The assessment of the quality of life by SF-36 scale demonstrates the absence of a statistically significant decrease in the quality of life of patients compared to the average indicators for the healthy population in the Russian population. Our data indicate that stroke before surgery has a statistically significant effect on the mental health of patients, a decrease in vital activity and leads to a significant decrease in social contacts of patients. At the same time, performing surgical intervention reduces the risk of developing stroke: the rate of freedom from neurological events in operated patients with damage to the branches of the aortic arch was 92.3±7.4%. Among the factors that statistically significantly reduce quality of life indicators are the development of restenosis and thrombosis of vascular grafts, multifocal type of damage to the aorta and its branches, and the presence of arterial hypertension.

Thus, patients with Takayasu arteritis require dynamic monitoring of the state of vascular reconstructions and correction of hypertension. When thrombosis and hemodynamically significant restenosis of grafts are detected, new vascular regions are involved, the issue of surgical treatment should be considered in order to restore blood flow in the affected area.

The aim of the work is to study the frequency and severity of cutaneous vasculitis (CV) in patients with infective endocarditis (IE), to analyze the relationship with damage to the heart valves, internal organs, and the outcome of the disease.

Materials and methods. Analysis of 359 patients with definite IE hospitalized from 2001 to 2019.

Results. CV syndrome of varying severity was detected in 69 patients, the frequency of CV in patients with IE was 19.2%. Skin rashes were noted in patients mainly in the form of symmetrically located petechial elements in the distal parts of the lower extremities (53 patients). In 15 cases, CV of a widespread nature was detected, and the primary skin elements were polymorphic. One patient was diagnosed with a bullous-necrotic form of CV. In the group of patients with IE and CV compared to patients with IE without skin symptoms, acute IE, intravenous drug use, coinfection with hepatitis C and B viruses, splenomegaly, kidney and eye damage, systemic embolism and neurological disorders were significantly more common (p<0.05). Patients with CV were distinguished by younger age, severity of anemia (decreased hemoglobin and red blood cell levels in 1 ml), daily proteinuria, increased serum transaminases, circulating immune complexes, erythrocyte sedimentation rate and C-reactive protein (p<0.05). No differences were found in the localization and number of affected heart valves, severity of heart failure, or rhythm disturbances in the study groups (p>0.05). 48 (69.5%) patients with IE and cutaneous vasculitis were discharged with significant improvement/stabilization of the condition of the underlying disease and a simultaneous decrease in skin manifestations, up to their complete disappearance against the background of antibacterial therapy. The risk of death is higher in the presence of cutaneous vasculitis (odds ratio – 2.32, 95% confidence interval: 1.27–4.3; p<0.05).

Conclusions. The presence of cutaneous vasculitis syndrome in patients with IE, especially at the onset of the disease, complicates timely diagnosis, can serve as a basis for differential diagnosis and should be taken into account when prescribing therapy and determining the tactics of managing patients with IE. With an established diagnosis of IE, skin symptoms often resolve against the background of standard antibiotic treatment.

Chronic shoulder pain (CSP) is a common pathology of the musculoskeletal system that causes suffering, a significant decrease in working ability and quality of life. One of the leading causes of CSP is traumatic injury to the tendons of the rotator muscles of the shoulder. The identification of factors contributing to the chronic pain in this pathology is of great importance for medical practice.

The purpose of the study: to determine the factors associated with the development of chronic shoulder pain after injury to the shoulder joint.

Material and methods. The study involved 202 patients with shoulder pain (51.5% of women; average age – 50.5±14.7 years) lasting up to 3 months, who were observed in the clinic of V.A. Nasonova Research Institute with a diagnosis of shoulder rotator compression syndrome. All patients had a history (within the last 6 months) of injury to the shoulder joint. Initially, the pain intensity averaged 5.82±1.51 on a numerical rating scale (NRS 0–10). Functional disorders were assessed according to the ASES (American Shoulder and Elbow Surgeons) and CSS (Constant – Murley Score) indices, the average values of which were 52.2±14.8 and 53.5±16.6, respectively. Subclinical depression and anxiety (≥8 according to the Hospital Anxiety and Depression Scale (HADS)) were 7.9% and 8.4%, signs of central sensitization (CS; score ≥40 according to the CSI-A (Central Sensitization Inventory Part A) questionnaire) – 11.9% of patients. The presence of CSP was determined in the case of persistent pain during movement in the shoulder joint ≥4 NRS on examination after 3-6 months. after the course of treatment.

Results. 81.1% of patients received nonsteroidal anti–inflammatory drugs (NSAIDs), 18.5% received local injection therapy with glucocorticoids (GK), 9.9% with hyaluronic acid (HA), 5.4% with platelet-rich blood plasma (PRP); physiotherapy and physical therapy were also performed. At the second visit, CSP was detected in 27.2% of patients. The development of CSP was not affected by the gender, age, body mass index of patients and anxiety according to HADS. Factors associated with CSP included initial severe pain (>7 NRS; odds ratio (OR) – 2.869; 95% confidence interval (95% CI): 1.496–5.503; p=0.002), ASES≤50 (OR=5.525; 95% CI: 2,801–10,899; p<0.001), CSS≤70 (OR=6.235; 95% CI: 1,434–27,135; p=0.006), depression (HADS≥8; OR=2.957; 95% CI: 1,051–8,520; p=0.042), CS (CSI≥40; OR=2.577; 95% CI: 1,077–6.164; p=0.048). The incidence of CSR was significantly reduced by local injection therapy with HA (OR=0.270; 95% CI: 0.061–0.925; p=0.048). Taking NSAIDs, local injection therapy with GK and PRP did not reduce the risk of developing CSP.

A clinical case of familial Mediterranean fever (FMF) in an adult patient of Armenian nationality is presented. In this case, the diagnosis was established only 9 years after the onset of clinical symptoms and confirmed by genetic testing, which revealed compound heterozygosity for the MEFV gene. The administration of colchicine at a dose of 1 mg per day completely eliminated the clinical manifestations of the disease. Observation confirms the need for caution regarding the development of FMF in representatives of vulnerable ethnic groups, even not in the regions of their compact residence.