Coxitis is one of the characteristic clinical manifestations of ankylosing spondylitis (AS). Hip joint (HJ) involvement in AS is considered an un-favorable prognostic factor. Early detection of coxitis is of great importance, since with the timely initiation of adequate treatment, the risk of developing irreversible changes in HJ can be reduced.

The lecture discusses the issues of clinical and instrumental diagnosis of coxitis in AS and presents an algorithm for its early detection developed by the authors.

Objective: To study the frequency of spontaneous foci of DNA double-strand breaks (DSBs) in patients with immune-inflammatory rheumatic diseases (IIRD), their relationship to disease activity, levels of inflammatory markers, and levels of autoantibodies.

Material and methods. The analysis included 40 patients with IIRD, including 19 patients with rheumatoid arthritis (RA, including 16 women, median disease duration 60 [20; 103] months, DAS28 was 5.05 [4.06; 5.9]) and 21 patients with systemic lupus erythematosus (SLE, 19 women, median disease duration 96.0 [40.0; 158.0] months, SLEDAI-2K 8.0 [4.0; 12.0]). The control group consisted of 17 healthy donors matched for sex and age.

DNA DSBs were identified as discrete foci by immunofluorescence staining of lymphocyte cultures with antibodies against γH2AX and 53BP1 and subsequently analysed using the automated AKLIDES automated platform (Medipan).

Results and discussion. There were no significant differences in the number of spontaneous DNA DSBs in patients with RA and healthy donors (p>0.05), a lower number of cells with the 53BP1 focus and a lower percentage of cells damaged in this focus were found in patients with SLE than in controls. There was a positive correlation between the number of γH2AXdamaged cells and CDAI(r=0.45, p=0.035), the number of cells with 53BP1 ruptures and the level of rheumatoid factor IgM (r=0.63, p=0.005) and ESR (r=0.53, p=0.02). In the group of SLE patients, a positive correlation was observed between the number of cells with breaks in the γH2AX focus and the level of antibodies against double-stranded DNA (anti-dsDNA; r=0.56, p=0.007), the average number of breaks in the cell in the γH2AX focus with the level of anti-dsDNA (r=0.57, p=0.004).

Conclusion. The number of DNA DSBs may be an additional indicator of IIRD activity. In patients with SLE, DNA repair processes appear to be impaired, which is associated with the high activity of the disease.

Citrullinated histone H3 (CitH3) is a specific marker for NETosis; its role in determining the clinical and laboratory manifestations of systemic lupus erythematosus (SLE) remains to be elucidated.

Objective: To evaluate the role of CitH3 in the development of clinical and laboratory manifestations in patients with SLE with and without an-tiphospholipid syndrome (APS).

Material and methods. The study included 30 patients with SLE and 39 with SLE+APS, including 51 (73.9%) women and 18 (26.1%) men. The median age of the patients was 36 [32; 46.5] years. The control group consisted of 26 healthy individuals.

SLE activity was assessed by the SLEDAI-2K index. Patients were divided into two groups: 41 patients with moderate and high SLE activity (SLEDAI-2K ≥6) were included in the first group, and 28 patients with low activity or remission (SLEDAI-2K <6) were included in the second group.

CitH3 content in blood serum was determined by enzyme immunoassay using a set of reagents for the assay of CitH3 (BlueGene Biotech, China) according to the manufacturer's instructions.

Results and discussion. CitH3 content in blood serum was significantly higher in SLE than in the control group (p=0.048). High blood serum CitH3 content was associated with moderate and high SLE activity (p=0.039). CitH3 concentration was inversely correlated with lymphocyte count but was not related to immunological parameters. Increased CitH3 levels were associated with photosensitivity, while lower levels were associated with a history of serositis. There were no significant differences between blood serum CitH3 levels in patients with SLE and SLE+APS (p=0.39).

Conclusion. The concentration of a specific marker for NETosis, CitH3, is increased in patients with SLE, and this increase is associated with moderate and high disease activity.

The efficacy of methotrexate (MT) in patients with rheumatoid arthritis (RA) may be determined by genetic factors.

Objective: to evaluate the isolated and combined effects of single nucleotide polymorphisms (SNPs) of membrane transporter proteins (RFC1 80G>A and MDR1 3435C>T) and the GGH -401C>T gamma-glutamyl hydrolase enzyme genes on the efficacy of MT in patients with RA.

Material and methods. The study group consisted of 85 patients with a confirmed diagnosis of RA, who received therapy with MT starting at 10 mg/week and increasing in dose to a maximum of 25 mg/week. Efficacy was assessed after six months of treatment using the dynamics of the DAS28 index, identifying patients who responded and those who did not respond to MT therapy.

Genotyping of RFC1, MDR1 and GGH gene polymorphisms was performed by real-time polymerase chain reaction. Three different approaches were used to analyze the results: 1) analysis for each of the genes; 2) logistic regression; and 3) multifactor dimensionality reduction (MDR).

Results and discussion. Single gene analysis was used to determine the most likely predictors of non-response to therapy: 1) for GGH-401C>T, TT genotype (odds ratio, OR 5.09; 95% confidence interval, C11.11—23.3); 2) forMDR13435C>T, the TT genotype (OR 2.38; 95% CI0.89-6.37); 3) for RFC180G>A, not - AA genotype (OR 1.87; 95% CI 0.93-3.76).

The logistic regression model showed a significant effect of homozygous genotype GGH -401TT on the efficacy of MT with low sensitivity of the method. The multifactorial dimensionality reduction results show a significant synergistic effect of the MT transport genes (MDR1, RFC1) and the GGH enzyme encoding the conversion of MT to the elimination form.

Conclusion. Using various statistical methods, the following results were obtained: Single gene analysis revealed the most likely predictors of nonresponse to MT therapy: GGH -401C>T - TT genotype, MDR1 3435C>T - TT genotype, RFC1 80G>A - not-AA genotype; the method of multiple logistic regression allowed to determine the significant effect of GGH -401ТТ genotype on the effect of the drug with a low sensitivity of the method; the isolated effect of polymorphisms is probably less pronounced than their combined effect on the effectiveness of MT. SNP synergism is a major contributor to the development of treatment resistance. MDR is a promising method that can be used in the future to assess the impact of SNPs.

In clinical practice, differences in the efficacy of tumor necrosis factor-α inhibitors (iTNF-α) have been observed in different diseases.

Objective: to evaluate the efficacy of iTNF-α in patients with immune-mediated diseases and its relation to the immunogenicity of these drugs.

Material and methods. The study included 70 patients with rheumatic diseases (RD) and 53 with inflammatory bowel disease (IBD) treated with infliximab (IFN), adalimumab, or certolizumab pegol (CZP). Disease activity and response to therapy were evaluated, as well as measurement of the minimal residual concentration of iTNF-α and the level of anti-drug antibodies.

Results and discussion. Therapy efficacy was maintained in 60 (85.7%) patients with RD and 35 (66.0%) with IBD (odds ratio, OR 1.3; p=0.01). Event-free survival of therapy was observed more frequently in RD and was longer than in IBD (p<0.01). The incidence of treatment failure was 3.13 times higher in IBD than in RD (p<0.01). In contrast to IBD, low TNF-α levels were more common in RD patients who did not respond to treatment than in those who did (80% and 40%, respectively; OR 6.0; p<0.05). Anti-TNF-α antibodies were detected in 75% of patients with ineffective treatment with INF and CZP in the RD group and in 14.3% in the IBD group (OR 0.06; p<0.05).

Conclusion. In patients with RD, the effect of iTNF-α lasted more frequently and longer than in patients with IBD. In ankylosing spondylitis and rheumatoid arthritis, the ineffectiveness of iTNF-α was associated with the formation of anti-drug antibodies or their low concentration in most cases, but in IBD only in half of the cases.

The clinical presentation of lobular panniculitis (PN) associated with calciphylaxis (CP, calcification) can vary widely and may be associated with joint and internal organs involvement, making the diagnosis of the disease difficult.

Objective: to evaluate the frequency and significance of CP in patients with PN using long-term prospective follow-up.

Material and methods. From 2018 to 2023, at the V.A. Nasonova Research Institute of Rheumatology 217 patients with referral diagnosis "erythema nodosum" or "panniculitis" were examined. In 19.3% of cases (9 men and 33 women aged 37 to 72 years) CP was confirmed with an average disease duration of 56.3±11.2 months. Clinical examination of patients was performed according to the standards recommended by the Russian Association of Rheumatologists. International criteria were used to confirm the diagnosis of systemic lupus erythematosus (SLE), idiopathic inflammatory myopathies (IIM), systemic sclerosis (SS), and lipodermatosclerosis (LDS). In 12 patients with indurations, pathological examination of biopsy specimens of skin and subcutaneous fatty tissue from the area of induration was performed, which allowed confirming the diagnosis of idiopathic lobular PN (ILPN) in 3 cases. 

Four grades of calcification were distinguished according to the size and depth of the calcifications. In addition, considering the type of radiological changes and clinical manifestations, four subtypes of CP were identified: mousse-like, stone-like, mesh-like and lamellar-like.

Results and discussion. In the study group, the ratio of women to men was 3.6:1, and the mean age was 43.8±7.6 years. On clinical examination we determined, in 60% of cases CP predominantly stone-like subtype (71.4%) of first grade (47.6%), which was significantly more frequently located on the upper and/or lower extremities and/or trunk (57.1%; p=0.05). Using clinical, laboratory and instrumental data, we confirmed the development of CP in ILPN (n=3), SLE (n=3), LDS (n=21), IIM (n=5), SS (n=1), and idiopathic CP (n=9) with a mean disease duration of 8.7±2.4 years.

An increase in ESR and CRP levels occurred in different diseases, while urinary syndrome was associated with SLE (66.6%) and an increase in creatinine phosphokinase with IIM. Decreased calcium and 25-hydroxyvitamin D levels and increased phosphorus and parathyroid hormone levels were found in many patients studied.

Conclusion. In the absence of clear diagnostic criteria for CP in patients with PN, early diagnosis is critical for the development of an effective multidisciplinary treatment plan.

The problem of clinical and immunological heterogeneity of systemic lupus erythematosus (SLE) is of great interest, especially the combination of SLE and Sjögren's syndrome (SjS) determines a more favorable prognosis and specifics of therapy.

Objective: to characterize the clinical and immunological features of SLE combined with SjS.

Material and methods. The retrospective study included 44 patients with SLE combined with SjS and 356 patients with SLE without SjS, hospitalized at the V.A. Nasonova Research Institute of Rheumatology between 2013 and 2021. The two groups of patients were compared in terms of life expectancy, clinical manifestations, laboratory parameters and therapy.

Results and discussion. The following phenotypic features of the clinical and immunological variant of SLE combined with SjS were found: significantly longer duration of SLE (p<0.01); higher incidence of polyarthritis (p=0.01) and Raynaud's syndrome (p<0.003) at disease onset. Subacute cutaneous lupus erythematosus, Raynaud's syndrome, peripheral nervous system involvement (sensory polyneuropathy and distal sensory-motor polyneuropathy) were found more frequently in SLE combined with SjS than in SLE without SjS, p<0.0001. Among laboratory abnormalities in SLE patients with SjS, leukopenia (p<0.0001), antibodies to SSA/Ro, SSB/La, and rheumatoid factor (p<0.0001) were observed in a greater number of cases. In the group of SLE combined with SjS, the chronic variant of SLE course according to the classification of V.A. Nasonova, and lower activity were observed, which didn't not require therapy with high doses of glucocorticoids; in this group, rituximab (p<0.01), cyclophosphamide and methotrexate were used significantly more often.

Conclusion. Thus, significant clinical and laboratory differences were found between SLE with SjS and without SjS. They determine prognosis, approaches to pathogenetic therapy and monitoring.

In patients with systemic sclerosis (SSc), interstitial lung disease (ILD) is a factor in the decline of functional capacity up to disability and is also the leading cause of death. Therefore, one of the most important tasks in the treatment of this group of patients is not only to detect involvement of respiratory system, but also to predict the likelihood of its development.

Objective: to study the possibility of predicting the development of ILD and advanced ILD in patients with SSc.

Material and methods. The study included 79 patients with SSc (mean age 64.4±11.5 years; 94.9% women) from the Registry of myositis, SSc and Mixed Connective Tissue Diseases (РЕМИССиС) who underwent high-resolution computed tomography (HRCT) of the lungs. Classification trees (CTr) were constructed to predict the development of widespread ILD using the CHAID algorithm (exhaustive). All patients were tested for antibodies against Scl-70 (anti-Scl-70), CENP-B (anti-CENP-B), and PmScl (anti-PmScl).

Results and discussion. ILD signs according to HRCT were detected in 53 patients. Fibrotic (34.2%) and cellular (15.2%) types of nonspecific interstitial pneumonia were the most common, and common interstitial pneumonia was less frequent (11.4%).The presence of ILD and advanced ILD (involvement of more than 20% of the lung parenchyma) were significantly associated with the detection of any autoantibodies, except anti-centromere antibodies, an increase in pulmonary artery systolic pressure, a decrease in forced vital capacity, diffusing capacity of the lungs, blood oxygen saturation at rest, and all parameters of six-minute walk test (6MWT), and complaints of shortness of breath. In addition, the presence of extensive ILD was also significantly associated with diffuse SSc and with SSc without skin manifestations.

In establishing the CTr, it was found that the development of widespread ILD was unlikely in individuals who were able to walk more than 440 m in 6MWT and had neither anti-Scl-70 nor anti-PmScl.

Significant associations were also found between the radiological pattern of ILD and the types of disease-specific antibodies.

Conclusion. The 6MWT data in conjunction with the results of testing for SSc-specific autoantibodies provide a very accurate prediction of the presence and extent of ILD. It is advisable to include these indicators in the algorithm for screening and monitoring patients with SSc.

Objective: To investigate the frequency, structure, and risk factors of comorbid infections (CI) in patients with spondyloarthritis (SpA).

Material and methods. The study included 332 patients with SpA. Patients were interviewed by the investigating physician, and additional information was obtained from medical records.

Results and discussion. Respiratory tract (RT) and ear, nose, and throat (ENT) infections ranked first in the structure of CI. Exacerbation of SpA after CI was found in 42% of patients, and more severe CI against the background of SpA was found in 83 patients. 63 cases of severe CI (SCI) were documented, 63.5% of which were infections of the RT and ENT organs. Predictors for the development of lower RT (LRT) and ENT organ infections were the use of biologic disease-modifying antirheumatic drugs (bDMARDs) in general (odds ratio, OR 2.018; 95% confidence interval, CI 1.221-3.335; p=0.006 and OR 1.761; 95% CI 1.1-2.819, respectively; p=0.018) and tumor necrosis factor-α (TNF-α) inhibitors in particular (OR 2.376; 95% CI 1.417-3.983; p=0.001 and OR 1.833; 95% CI 1.123-2.994; p=0.015), and disease duration of more than 5 years (OR 1.774; 95% CI 1.034—3.042; p=0.037 and OR 2.22; 95% CI 1.378-3.576; p=0.001). The risk of developing LRT infection was higher in the presence of chronic lung disease (OR 3.673; 95% CI 1.602-8.425; p=0.002) and Charlesson Comorbidity Index ≥1 (OR 2.381; 95% CI 1.439-3.94; p=0.001), risk of developing ENT organ infections - with the use of >1 bDMARD (OR 2.4; 95% CI 1.199-4.804; p=0.013) and duration of methotrexate therapy over 5 years (OR 2.478; 95% CI 1.053-5.831; p=0.038). Risk factors for the development of SCI were the use of bDMARDs in general (OR 1.941; 95% CI 1.063-3.545; p=0.031) and TNFα in particular (OR 2.246; 95%, CI 1.218-4.139; p=0.01).

Conclusion. The problem of CI in SpA is of great importance. The vast majority of patients with SpA should be vaccinated against pneumococcal infection and influenza.

Objective: to study the course of COVID -19 and post-covid syndrome (PCS) in patients with rheumatoid arthritis (RA).

Material and methods. The study included 32 adult patients with a confirmed diagnosis of RA, who met ACR/EULAR criteria. All patients had COVID-19. Material for analysis was obtained by means of a questionnaire developed at the V.A. Nasonova Research Institute of Rheumatology, which patients completed during their interview with the researcher.

Results and discussion. The study group consisted mainly of women (n=29, 90%). The mean age of the patients was 50.75±16.48 years. Among the clinical manifestations of COVID-19, weakness/fatigue (90.6%; p<0.0001), fever (71.9%; p=0.0005) and anosmia (62.5%; p=0.045) were significantly more common. Almost half of the patients had dysgeusia (59.4%), increased arthralgia (53.1%), dyspnea on exertion (50%), and cough (46.9%). A significant positive association was found between increased arthralgia during COVID-19 and RA activity (r=0.72; p<0.05). Hospitalisation was required in 37.5% of patients with COVID-19. In 12.5% of cases, COVID-19 progressed with complications. Patients with higher RA activity were more likely to have an increase in arthralgia as a symptom of infection. PCS was registered in 47.8% of patients who underwent COVID-19. Retrospective evaluation of patients with PCS revealed a higher rate of hospitalisation in infectious disease departments and a more severe course of COVID-19. Subsequently, repeated cases of COVID-19 were more common in this group.

Conclusion. Risk assessment of PCS development is necessary to appropriately distribute the burden on the health care system and to develop a strategy for prevention, timely diagnosis, and treatment of this syndrome in patients with rheumatic diseases. To achieve this goal, new studies in a larger cohort of patients with RA and rheumatic diseases in general are needed.

Osteoarthritis (OA) is one of the most important medical and social problems due to the steady increase in morbidity and disability. Prevention, management of risk factors, and early treatment of OA are critical.

Objective of the ISKRA study was to evaluate the efficacy of Alflutop in patients with OA of different locations and/or low back pain (LBP) with or without concomitant diseases.

Material and methods. We selected 11,136 patients with OA of specific localizations aged 50 to 72 years. The duration of the study ranged from 20 to 31 days, and the number of visits was 2 (B1 and B2). Alflutop was prescribed 1 ml intramuscularly (IM) daily No. 20 or 2 ml IM every other day No. 10.

The efficacy of therapy was determined by the time of onset of clinical effect (pain reduction, as assessed by the patient), the dynamics of pain intensity in the studied joint during movement and/or LBP according to the visual analogue scale (VAS), the assessment of quality of life according to the EQ-5D questionnaire and the patient's general health status (PGH) according to VAS. We assessed treatment adherence, need for nonsteroidal anti-inflammatory drugs (NSAIDs), satisfaction with treatment (based on VAS). The presence of comorbidities was also considered.

Results and discussion. In hand OA (n=2776), a positive effect of therapy was observed in 98.6% of cases, according to patients' assessment. During the course of therapy, there was a significant decrease in pain on movement in the hands (according to VAS), improvement in PGH and quality of life (according to EQ-5D). Rapid development of the analgesic effect was seen on average at day 9.

In hip OA (n=6666), a decrease in pain was noted in 83.3% of cases (<40 mm), improvement in PGH and quality of life in most patients, and a decrease in the need for NSAIDs in 64.9%.

In the generalized form of OA (n=1694), significant clinical improvement was achieved in 97.1% of patients. A pain reduction ≥50% from baseline was noted in nearly 65% of cases.

Elderly age, more severe radiographic manifestations of OA, low quality of life and compliance, and concomitant diseases were associated with a lower effect of therapy in hand and hip OA. In hand OA, high pain scores and worse PGH VAS scores also played a role. In hip OA, lower success was observed more often in women, and in hand OA — in men.

In the generalized form of OA, lower satisfaction with pain management was associated with age, female sex, high body mass index, long history of OA, advanced radiographic stages, poorer quality of life and compliance, and comorbidity.

Conclusion. The results of the use of Alflutop in hand and hip OA and generalized form of OA suggest the usefulness of its wide application in real clinical practice. Consideration and correction of the factors associated with less pronounced analgesic effect of the drug will improve the effectiveness of OA therapy.

We present a clinical observation of a patient whose cause of death was a new coronavirus infection COVID-19 complicated by bilateral viral interstitial pneumonia and adult acute respiratory distress syndrome. The presence of background diseases-rheumatoid arthritis and secondary AA-adrenal amyloidosis-worsened the prognosis. Waterhouse-Friderichsen syndrome with hemorrhage and foci of necrosis in the adrenal cortex developed against a background of SARS-CoV-2 infection. The unique feature of this case is the long-term favorable course of the disease and its rapid progression after infection with SARS-CoV-2. The associated syndrome of disseminated intravascular coagulation further aggravated the patient's condition.

In juvenile onset systemic lupus erythematosus (SLE), musculoskeletal involvement is one of the most common manifestations. Musculoskeletal symptoms may be due to disease activity itself, organ damage due to SLE activity, drug exposure, or comorbidities. Although they are not life-threatening, they still have a significant impact on disability severity and social exclusion. This article discusses the clinical features of various causes of musculoskeletal manifestations in SLE with onset in childhood and adolescence, the adequate interpretation of which is important for diagnosing and evaluating SLE activity and for correcting the treatment of the disease, thereby improving the long-term prognosis and quality of life of patients.

Gout is associated with a high risk of cardiovascular diseases and associated mortality. Possible causes of the disease include persistent uncontrolled hyperuricemia, a chronic microcrystalline inflammation that develops in the vascular wall and even in atherosclerotic plaques. These processes, which contribute to oxidative stress and the formation of peroxidation products, may be a target for xanthine oxidase inhibitors — allopurinol and febuxostat. Their rational use, aimed at complete dissolution of urate crystal deposits in gout patients, results in improvement of endothelial function, lowering of blood pressure, and possibly reduction of all-cause and cardiovascular mortality. The effects on cardiovascular risk and safety of these drugs are believed to be comparable, greatly expanding the options for gout therapy.

The review considers the full spectrum of currently known autoantigens in osteoarthritis (OA) and discusses their role in the development and/or persistence of synovitis and the initiation of subsequent destruction of articular cartilage with the development of an autoimmune response and auto-inflammation. Of great interest are methods of drug prevention of OA considering autoimmunity responses and associated auto-inflammation, including the use of pharmaconutraceuticals.

Preclinical and clinical studies of the safety and efficacy of pharmaconutraceuticals containing native type II collagen are presented. A clear relationship between the composition/chemical structure of the collagen components and its mechanism of action and efficacy is discussed. Taking into account the autoimmune pathogenesis of OA, new combined pharmaconutraceuticals aimed at reducing the manifestations of autoinflammation (chondroitin sulfate, glucosamine sulfate) are developed. They have an optimal ratio of active ingredients with a sufficient level of evidence, which allows enhancing their beneficial pharmacological effects.

At the meeting of the Expert Council on May 20, the safety of treatment for patients with osteoarthritis (OA), the most common form of joint disease, was discussed. The first step in the treatment of OA should be the administration of symptomatic delayed-acting agents (SYSADOA) and nonsteroidal anti-inflammatory drugs (NSAIDs). However, given the current understanding of the pathogenesis of inflammation, as well as the fact that it is an active process involving multiple proinflammatory and pro-resolving mediators, it is reasonable to limit the cyclooxygenase-2 suppressive treatment and to include medications with multipurpose effects that contribute to the resolution of inflammation, in particular Zeel® T and Traumeel® S. Traumeel® S affects all stages of inflammation, mostly on the pro-resolving mediators synthesis, and Zeel® T affects chondrogenesis, inflammation, metabolic processes in cartilage tissue and prevents angiogenesis.

It was found that it is advisable to use Traumeel® S when it is not possible to prescribe systemic NSAIDs for pain relief. The combination of the proven therapeutic efficacy of Zeel® T and Traumeel® S with a minimal number of adverse events and the absence of interactions with other drugs allows them to be used as an independent treatment regimen for OA.

Local injection therapy (LIT)  is an important component of the complex treatment of musculoskeletal disorders (MSD), which is widely used in real clinical practice. Glucocorticoids, hyaluronic acid drugs (HA), autologous cell drugs, botulinum toxin type A, radioactive isotopes, etc. are used for LIT.  LIT makes it possible to achieve a pronounced symptomatic effect, while in some cases, for example, repeated HA treatments in patients with osteoarthritis, the possibility of slowing the progression of the disease and reducing the need for surgical treatment is discussed.

The performance of LIT requires special skills and abilities of the physician, careful compliance with the rules of asepsis and antisepsis, and instrumental visualization. LIT can be associated with serious complications and therefore must be performed according to strict indications.

The Expert Council was devoted to defining the basic principles of LIT. The indications for the use of certain types of this therapies, the evidence base for its efficacy and safety, the order of application of different drugs, and the need to combine LIT with other drug and non-drug treatments of MSD were reviewed.