Lung disease is one of the most common manifestations of systemic autoimmune rheumatic diseases (SARDs), involving all parts of the respiratory system in the pathological process. Interstitial lung diseases (ILD) are of great importance and often lead to the development of progressive pulmonary fibrosis (PPF). The following clinical categories of patients are distinguished within ILDs associated with SARDs (ILD-SARDs): ILD in patients with a reliable diagnosis of SARDs; ILD as the first manifestation of SARDs; ILD or interstitial pneumonia with autoimmune features. Clinical phenotypes of ILD-SARDs vary from «asymptomatic» to «rapidly progressing» are related with risk factors for progressive lung damage. These phenotypes should be considered for conducting clinical, laboratory and instrumental screening and prescribing anti-inflammatory or antifibrotic therapy. In the pulmonology practice a patient with ILD may have previously established SARDs, or this diagnosis could be suspected based on a number of clinical symptoms of rheumatic diseases. Problem of ILD-SARDs diagnostic is very complex, which determines a multidisciplinary approach based on the interaction with rheumatologists, pulmonologists and radiologists. The possibilities and perspectives for pharmacotherapy of ILD-SARDs are based on the rational use of anti-inflammatory, immunomodulatory and antifibrotic drugs. The following issues related to pharmacotherapy of ILD-SARDs should be emphasized: identification of patients with a rapidly progressing phenotype of pulmonary fibrosis; the contribution of inflammatory activity; the effectiveness of therapy in relation to the leading “extrapulmonary” manifestations of SARDs and pneumotoxicity within the implementation of the “treat to target” concept. The greatest achievement in the pharmacotherapy of autoimmune diseases is associated with the use of chimeric antigen receptor (CAR) T-cell therapy, which mechanism is associated with the elimination of pathogenic autoreactive B-cells. Preliminary data of CAR T-cell therapy indicate the high efficacy in a wide range of clinical manifestations of SARDs, including the progression of ILD in patients with systemic sclerosis and antisynthetase syndrome, and there are strong evidence of the important role of autoimmune mechanisms in the pathogenesis of ILD.

The article discusses the 2022 updated version of the collaborative ASAS/EULAR (Assessment in SpondyloArthritis international Society/European Alliance of Associations for Rheumatology) recommendations for the treatment of axial spondyloarthritis.

Chronic pain is the main manifestation of rheumatoid arthritis (RA), determining the severity of suffering and functional impairment. Although pain in RA is primarily associated with autoimmune inflammation, it can persist against the background of low activity and even remission of the disease. This makes it necessary to search for the causes and peculiarities of the development of chronic pain in RA. It seems that the classification of pain types in RA can help in personalizing approaches to its medication control. In this regard, the evaluation of the relationship between pain and the cellular composition (pathotype) of synovitis in RA is of great interest. Three main pathotypes are known: lymphoid (with predominance of T and B lymphocytes, plasmocytes), myeloid or diffuse-myeloid (with predominance of macrophages, monocytes, granulocytes) and pauci-immune (mainly consisting of fibroblast-like synoviocytes (FLS)). The lymphoid pathotype is characterised by high positivity for rheumatoid factor and anti-citrullinated protein antibodies, severe RA activity and intense pain, including that associated with polyneuropathy and dysfunctional disorders; the myeloid pathotype is characterized by less severe activity and local nociceptive pain; the pauci-immune pathotype is characterized by moderately severe pain and peripheral hyperalgesia against a background of moderate/low disease activity. The last pathotype can determine chronic pain in seronegative RA and at late stages of the disease, in which marked structural changes are noted. Currently, there is no clear view on drug approaches for the different pathotypes of synovitis in RA. There is limited evidence for the use of CD20 inhibitors (rituximab) and interleukin (IL) 6 inhibitors in the lymphoid pathotype, and IL-6 and tumour necrosis factor α inhibitors in the myeloid pathotype. Currently, active development of drugs to target FLS is underway. The data of some studies indicate higher efficacy of IL-6 inhibitors in pauci-immune pathotype.

Uveitis is a common extra-skeletal manifestation of ankylosing spondylitis (AS) and other spondyloarthritis (SpA). The recurrent course of uveitis in SpA contributes to the development of complications affecting vision. Timely treatment of uveitis exacerbation and prevention of relapses is an important component of SpA management. The article discusses approaches to modern anti-inflammatory therapy of uveitis in SрA, including traditional and targeted drugs. The data from clinical studies on the effect of various treatment regimens on the course of uveitis in SpA are presented, as well as a comparative assessment of the effectiveness of biologic and targeted synthetic drugs.

The aim of the study is to evaluate the efficacy, safety and immunogenicity of divozilimab (DIV), anti-CD20 monoclonal antibody, in patients with systemic sclerosis (SS).

Materials and methods. Patients with SS according to ACR/EULAR (American College of Rheumatology/ European Alliance of Associations for Rheumatology) 2013 criteria with modified Rodnan skin score (mRSS) ≥10 and ≲20 and forced vital capacity (FVC) ≥40% from the due took part in the study. Infusions of DIV 250 mg were administered on weeks 0 and 2, and DIV 500 mg – on week 24 with the subsequent use in open mode, starting from week 48. This publication presents data obtained for 48 weeks of trial (before the DIV infusion at week 48). Primary endpoint was the change in the mRSS from baseline to week 48. The dynamic of FVC was estimated as the secondary endpoint. The safety evaluation included the frequency and profile of adverse events and adverse reactions (ARs). Immunogenicity was assessed by detection of binding and neutralizing anti-drug antibodies on weeks 2, 24 and 48.

Results. 151 patients were randomized into two groups: DIV (n=76) and Placebo (n=75). The most were female; the median duration of the disease was about 3–4 years. The initial value of the mRSS was 14 and 13 points in DIV and PBO groups, respectively. The change of mRSS from baseline to week 48 was –5.8±1.1 points in DIV group and –2.7±1.0 points in Placebo group (adjusted mean difference (AMD) with 95% confidence interval –3.1 (–4.5; –1.7); p<0.0001). The lung function was stable in patients treated with DIV. A comparable safety profile of DIV and PBO was demonstrated. The most frequent ARs were infusion reactions and a decrease in the number of lymphocytes. There were no severe and serious ARs in DIV group. All infusion reactions were mild and moderate. 5.3% (4/76) patients in DIV group had binding antibodies without neutralizing activity.

Conclusion. Divosilimab has demonstrated a significant decrease in severity of skin fibrosis, a positive effect on the respiratory function and a favorable safety profile, which allows to consider it as a promising therapeutic option for SS. 

The aim – to determine the clinical significance of hyperproduction of antibodies to the NR2 subunit of glutamate N-methyl-D-aspartate receptors (aNMDAR) in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS).

Material and methods. The study included 66 patients with reliable diagnoses of SLE and APS (SLE – 24 patients; SLE+APS – 18 patients, primary APS – 24 patients). Young women (35.5±10.2 years) prevailed (72.7%). All patients were examined according to the standards recommended by the Association of Rheumatologists of Russia, and also examined by a psychiatrist. Neuropsychiatric syndromes, mainly psychiatric, were detected in 62 (93.9%) patients. aNMDAR was determined in all patients and 20 healthy donors, matched by gender and age, by enzyme immunoassay in blood serum.

Results. The concentration of aNMDAR in patients with neurological manifestations of SLE and APS did not exceed the threshold value, but was significantly higher than in healthy donors (4.32±2.0 versus 2.96±1.44 ng/ml, respectively; p=0.042). Patients with elevated aNMDAR concentrations had a statistically significantly higher (p<0.05) probability of detecting neurological manifestations such as acute/transient cerebrovascular accident/epilepsy (odds ratio (OR) – 9.0), as well as bipolar affective disorder (OR=14.0), and statistically not significantly – schizotypal disorder (OR=3.8) and moderate cognitive impairment (organic type) (OR=2.15). The probability of detecting APS in patients with elevated aNMDAR values was 1.7 times higher, the risk of thrombosis according to the GAPSS (Global Anti-Phospholipid Syndrome Score) was 4.28 times higher, and aPL positivity (aCL, aß2GP-1, aFs/Pt) and a-ds-DNA – 2.5–6.73 times (the differences were not statistically significant).

Conclusion. aNMDAR may play an important role in the development of certain neuropsychiatric manifestations in patients with SLE and APS. It is advisable to conduct larger-scale studies aimed at confirming the need to identify aNMDAR as a biomarker for the diagnosis and monitoring of the progression of neuropsychiatric manifestations of SLE and APS.

Background. Сhronic inflammation is one of the main factors in the progression of systemic sclerosis (SSc). Macrophages activated via a proinflammatory pathway can be considered as major participants in the maintaining of system chronic lowgrade inflammation.

The aim of this study was to evaluate the inflammatory response and of macrophages in patients with systemic sclerosis to reveal the most significant inflammatory mediators in pathogenesis of this disease.

Materials and methods. The study included 34 treatment-naive SSc patients and 17 controls. Macrophages were obtained by culturing peripheral blood monocytes. The macrophage response was analyzed by deviations in the parameters of basal, lipopolysaccharide (LPS) stimulated, and restimulated secretion of the tumor necrosis factor α (TNF-α), interleukin (IL) 1β, C-C motif ligand 2 (CCL2), and IL-8 by cultured macrophages in SSc patients compared to the control group. The levels of basal and LPS-stimulated secretion were assessed on day 1. The second LPS stimulation was performed on day 7 to assess the cell response to repeated stimulation (restimulated secretion) after the first stimulation to characterize the resistance of the macrophage immune response. Cell resistance (tolerance) was calculated as the ratio of secretion during repeated stimulation to LPS-stimulated secretion. Concentrations of TNF-α, IL-1β, CCL2, and IL-8 cytokines in the culture fluid were determined out using an enzyme-linked immunosorbent assay.

Results. Basal and restimulated secretion of all studied cytokines was significantly higher in the SSc group compared to the control group; LPS-stimulated secretion was statistically significantly higher in the SSс group only for IL-1β. Impaired resistance of the immune tolerance of macrophages to CCL2 was detected in 50% of treatment-naive SSc patients.

Conclusions. The results of the study demonstrate a pro-inflammatory response of macrophages with increased levels of basal and restimulated secretion of TNF-α, IL-1β, CCL2 and IL-8, as well as impaired tolerance of the immune response of macrophages in treatment-naive SSc patients in relation to the secretion of CCL2. These data indicate the active participation of CCL2 in the development of chronic inflammation in SSc that can be considered as a target for the development of new therapeutic approaches for SSc.

The aim – to determine the level of sST2 in patients with systemic lupus erythematosus (SLE), its relationship with traditional rick factors (TRF) of cardiovascular diseases (CVD), clinical and immunological manifestations of SLE, echocardiography (ECHO) parameters, including global longitudinal strain of left ventricle (GLS LV).

Subjects and methods. The study included 100 patients with a reliable diagnosis of SLE. The average age was 33.2±9.3 years, the median (Me) duration was 1.5 [1.0; 8.7] years. The median SLE activity according to the SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index 2000) was 8 [4; 10] points. The level of sST2 was measured in the blood serum of all patients. All patients underwent ECHO with an assessment of GLS LV using the speckle tracking. The control group consisted of 30 healthy people of comparable age and gender.

Results. In patients with SLE, the sST2 level is higher than in the control (10.03 [6.6; 16.03] and 7.0 [5.3; 10.6] ng/ml (p<0.003)). Patients with SLE were divided into 2 groups: group 1 – sST≥18.8 ng/ml (n=20); group 2 – sST<18.8 ng/ml (n=80). Patients in group 1 were younger, had higher levels of diastolic blood pressure and uric acid, hypertension was more common (25% and 6.3%, respectively), CVD heredity (45% and 20%, respectively), nephritis (50% and 21.3%, respectively) compared with group 2. GLS LV was lower in group 1 (–17.0 [–15.2; –19.5]% and –18.7 [–17.7; –20.7]%, respectively; р=0,016). sST2 corelated with SLEDAI-2K (r=0.325), glucocorticoid dose (r=0.353), anti-DNA level (r=0.328), anti-Sm (r=0.253) (p<0.05 in all cases). According to multifactorial analysis, nephritis, triglyceride level, serositis, low-density lipoprotein level, and heart rate correlate with sST2.

Conclusion. In patients with SLE, the sST2 level is increased in comparison with control. sST2 increase related with TRF, clinical and immunological manifestations of SLE. In patients with SLE and low GLS LV, the sST2 level was higher. In patients with SLE, subclinical myocardial damage develops at an early stage of the disease.

Connective tissue dysplasia (CTD) is a genetically determined disorder of the development of connective tissue in the embryonic and postnatal periods, which is characterized by defects in the structure of the fibers and basic substance of the connective tissue, which can cause a variety of disorders in the functioning of the internal organs and the musculoskeletal system. Today, there are two main groups of CTD: differentiated (monogenic, hereditary) and undifferentiated (multifactorial). More than 250 hereditary variants of CTD have been described in the literature, one of which is osteogenesis imperfecta (OI), a disease characterized by frequent low-traumatic bone fractures, hear- ing impairment, pathology of tooth enamel, and blue coloration of the sclera of patients. However, data on the presence of other clinical manifestations of CTD, i. e. about the systemic involvement of connective tissue are fragmentary.

Aim of the study – to analyze the frequency of occurrence of phenotypic signs of connective tissue dysplasia in adult patients with osteogenesis imperfecta and to develop an algorithm for clinical diagnostics.

Materials and methods. A single-stage cross-sectional comparative study was conducted on 40 patients with osteogenesis imperfecta and 45 healthy controls at the Clinic of the Bashkir State Medical University. Joint hypermobility (JH) was determined using the Beighton scale; connective tissue dysplasia was assessed using a modified table by T.I. Kadurina. Bone mineral density was determined using X-ray densitometry.

Results. Statistically significant differences in the frequency of occurrence of phenotypic signs of CTD were revealed: temporomandibular joint crunching (р<0,001), dental enamel pathology (р<0,001), JH (p=1.4×10–4), kyphoscoliotic deformity of the spine (p=1.1×10–4), chest deformity (p=0.010), valgus feet (p=0.005), joint crunching (p=0.023), mitral valve prolapse (p=0.005) and arterial hypotension (p=0.021). Statistically significant differences in bone mineral density in absolute values (р<0,001) and Z-criterion levels (р<0,001) were also observed.

Conclusions. In patients with OI, statistically significantly more frequent phenotypic manifestations of CTD were revealed. For patients with type I OI, hemorrhagic manifestations are typical, as well as ptosis of internal organs. In type III, spinal deformities are characteristic, chest deformities were more often observed in patients with type V OI. A clinical algorithm for determining OI types was developed to optimize diagnostics and genotyping.

The aim – to compare the efficacy and safety of different doses of colchicine (0.5 mg/day vs 1.0 mg/day) used for the prevention of arthritis attacks in gout patients during the initiation of urate-lowering therapy.

Materials and methods. The study included 96 patients diagnosed with gout. Patients were randomized into three groups: those receiving colchicine 0.5 mg/day, colchicine 1 mg/day, and those without anti-inflammatory therapy. All participants were prescribed febuxostat 80 mg/day. The duration of the observation period was 6 months. The frequency and severity of arthritis attacks, as well as the incidence of adverse events, were compared.

Results. Patients who did not receive colchicine experienced arthritis attacks more frequently compared to those receiving 0.5 mg/day (p=0.03) and 1 mg/day (p=0.007). In the groups receiving colchicine 0.5 mg/day and 1.0 mg/day, the frequency of attacks did not differ significantly (p=0.6), nor did the proportion of patients who did not experience arthritis attacks – 18 (56%) and 22 (69%), respectively (p=0.3). Among patients not taking colchicine, 9 (28%) did not develop arthritis attacks (p=0.02 compared to those taking 0.5 mg/day and p=0.001 for 1 mg/day). The administration of colchicine 1 mg/day (but not 0,5 mg/day) was associated with lower pain intensity on the visual analog scale during arthritis attacks compared to the non-therapy group (p=0.04). The frequency of adverse events was comparable across the groups.

Conclusion. The use of colchicine 0.5 mg/day for the prevention of arthritis attacks in gout patients is justified due to the absence of differences in efficacy compared to the higher dose. However, prescribing colchicine 1 mg/day also demonstrates a good safety profile and may be considered for the prevention of arthritis attacks.

Currently, the problem of posttraumatic pain is widely discussed in domestic and foreign publications, however, the fact of frequent formation after traumatic exposure of not just chronic pain, but such a complex and multifaceted condition as fibromyalgia is currently little discussed. At the turn of the 20th and 21st centuries, the term “posttraumatic fibromyalgia” was often mentioned in English-language publications, and is currently not widely used in modern literature. Data on medicinal and psychotherapeutic methods of treating fibromyalgia are widely presented in scientific publications, whereas methods of physical and rehabilitation medicine in the treatment of fibromyalgia are clearly not given enough attention. In a brief descriptive review, we will try to figure out whether the concept of “posttraumatic fibromyalgia” is legitimate and present up-to-date data on the effectiveness and safety of physical and rehabilitation medicine methods in the treatment of fibromyalgia.