Vaccination plays an important role in the prevention of infectious diseases in patients with immunoinflammatory diseases. When vaccinating patients with systemic lupus erythematosus (SLE), as with other immunoinflammatory rheumatic diseases, its safety is of great importance, including mitigating the risks of the primary disease or the development of new autoimmune phenomena. Many practitioners continue to consider autoimmune diseases as a contraindication for vaccination due to the perceived possibility of their exacerbation and reduced vaccine effectiveness during active immunosuppressive therapy.

The lecture presents current data on the immunogenicity, efficacy and safety of vaccines against a number of infections caused by influenza viruses, hepatitis B, Herpes zoster, human papilloma viruses, COVID-19 and pneumococcus in patients with SLE. It has been shown that the benefits of vaccination in patients with SLE significantly outweigh the risk of adverse events or exacerbations of the disease. At the same time, it was noted that the problem of vaccination of such patients requires further study.

Objective: to compare the course of the disease and therapy in rheumatoid arthritis (RA) patients who meet and do not meet the criteria for difficult- to-treat RA (D2T).

Patients and methods. The study included RA patients who met the 2010 ACR/EULAR criteria and who were hospitalized in the V.A. Nasonova Research Institute of Rheumatology from March to October 2021. All patients underwent a conventional clinical and laboratory examination, radiography of the hands and distal feet, and the radiological stage of RA according to Steinbroker was assessed. To determine the inflammatory activity, the DAS28-ESR and DAS28-CRP indices were calculated.

Results and discussion. The study included 303 patients with RA, 25 (8.4%) of them had D2T RA. The duration of RA in the D2T group was significantly longer than in other patients (15.9±11.8 and 11.9±9 years, respectively; p=0.04). X-ray changes in the joints in D2T were more pronounced. Patients with D2T had higher inflammatory activity at the time of hospitalization than patients who had continued prior therapy with biologic/targeted synthetic DMARDs. The dose of glucocorticoids (GC) in patients with D2T RA was higher compared to patients of other groups: on average 8.3±5.1 and 6.4±2.9 mg/day, respectively (p=0.02).

Conclusion. The results of this study suggest that in Russia, as well as abroad, the treat-to-target principle has not yet become widespread, and the selection of adequate therapy takes too much time. At the same time, Russian rheumatologists primarily use GC to suppress inflammatory activity. The introduction of modern recommendations for the management of patients with RA into routine clinical practice, could possibly restrain the formation of D2T RA.

Objective: the albumin to fibrinogen ratio (AFR) and the C-reactive protein (CRP) to albumin ratio (CAR) have been proposed as markers of systemic inflammation. The goal of this study was to differentiate rheumatoid arthritis (RA) patients from healthy people and to study the association between AFR/CAR and DAS28 in RA.

Patients and methods. A case control study including 30 RA patients and 30 healthy controls was performed. Fibrinogen, albumin, CRP and erythrocyte sedimentation rate (ESR) were measured. We calculated CAR and AFR in each group and compared them. Correlations of AFR, and CAR with disease activity were examined. Receiver operation characteristic (ROC) curves of AFR and CAR were also used to detect cutoffs for disease activity assessment.

Results and discussion. CAR was higher while AFR was lower in RA patients than in control group. ROC curve analyses showed that CAR can be used to detect disease activity of RA at cut off 2.66 with sensitivity 81.3% and specificity 64.3% with an area under the curve (AUC) 0.78. So, CAR was a fair parameter to discriminate disease activity among RA patients. AFR has AUC 0.62, sensitivity 87.5% and specificity 42.9% at cutoff value 5.96. So, in our group AFR was a poor indicator to discriminate disease activity among RA patients.

Conclusion. AFR and CAR have been recently proposed as inflammatory markers for assessment of disease activity in RA. AFR and CAR are simple, and inexpensive biomarkers, they also can be rapidly evaluated. CAR was found to be a fair parameter to depict disease activity in RA patients. AFR poorly depicted RA activity.

Psoriasis (PsO) is a chronic immune-mediated disease, in the pathogenesis of which various risk factors (RFs) and genetic predisposition play an important role. The complex interaction of genetic and trigger factors leads to the development of autoimmune and autoinflammatory reactions. Every fourth patient with skin PsO develops psoriatic arthritis (PsA), which, progressing and left untreated, can cause irreversible functional disorders, which necessitates early diagnosis of this disease.

Objective: to identify endogenous risk factors for the development of PsA.

Material and methods. We searched PubMed (MEDLINE), EMBASE, and Google Scholar databases for articles on endogenous risk factors for the development of PsA that were published over the past 10 years (until March 1, 2021). We searched for currently registered trials in the registers of clinical trials of US (ClinicalTrials.gov), of China (Chinese Clinical Trial Registry) and the WHO International Clinical Trial Registry Platform. The statistical analysis was prepared in accordance with the international guidelines for systematic reviews and meta-analysis (PRISMA) using the Statistic SPSS 26.0 program (USA). Meta-analysis was prepared using RevMan 5 software.

Results and discussion. Part 2 of the systematic review included 56 articles on endogenous risk factors for the development of PsA. When preparing a meta-analysis, a statistically significant increase (1.68 times) in the risk of developing PsA in the presence of psoriatic lesions of the scalp was noted (95% confidence interval, CI 1.09–2.61). There was no statistically significant increase in the risk of developing PsA in the presence of inverse PsO. The mean PASI was significantly higher (mean difference 2.64; 95% CI 1.37–3.91) in patients with PsA compared with patients without this disease. Mean duration of illness was also longer (mean difference 2.64 years; 95% CI 1.34–4.50) in patients with PsA than in patients with PsO.

Conclusion: PsO and PsA are multifactorial diseases. RFs not only affect their development, but also determine the characteristics of the clinical course, severity, and the presence of complications. Understanding the risk factors of the development of PsA is important for assessing the prognosis, timely diagnosis, and early initiation of therapy, which will prevent severe forms of the disease and disability in patients.

The formation of chronic musculoskeletal pain (MSP) is a multifactorial process, in its pathogenesis mechanism of central sensitization (CS) plays an important role.

Objective: to evaluate the effectiveness of etoricoxib at a dose of 60 mg per day in diseases accompanied by moderate/severe chronic MPS, with an additional analysis of the effect of this drug on the manifestations of CS.

Patients and methods. An open observational study, 790 patients (71.6% women, mean age 54.5±13.0 years) with osteoarthritis and chronic nonspecific back pain received etoricoxib 60 mg/day for 2 weeks. The dynamics of pain, dysfunction, fatigue, sleep disturbances, general health assessment (GHA) on a numerical rating scale (NRS 0–10), as well as signs of CS according to part A of the CSI questionnaire were assessed.

Results and discussion. After 2 weeks, the intensity of pain during movement, at rest and at night decreased on average by 58.8±24.1, 69.7±32.6 and 70.1±32.8% respectively; functional insufficiency by 58.2±22.5%, fatigue by 52.2±25.8%, GHA by 50.0±22.6%, sleep improvement by 54.3±25.8% was observed (p<0.001 for all parameters). There was a decrease in the CSI value by an average of 33.1±14.5% (p<0.001), as well as a decrease in the number of patients with highly probable CS (CSI ≥40) from 35.3 to 10.3% (p<0.001). No serious drug-related complications were recorded. The overall frequency of adverse reactions was 5.9%, with dyspepsia and hypertension being the most common.

Conclusion. Etoricoxib is an effective and relatively safe treatment for chronic MSP. It reduces the severity of CS, one of the central mechanisms of the pathogenesis of chronic MSP.

Objective: to evaluate the impact of undifferentiated connective tissue dysplasia (CTD) on the clinical manifestations of primary osteoarthritis (OA) in postmenopausal women.

Patients and methods. The case-control study included 38 postmenopausal women with primary knee OA, radiological stage II. The main group included 19 patients who met the criteria for CTD, the control group included 19 patients without CTD.

Results and discussion. Patients in the control group had significantly higher values of body mass index, hip circumference and more pronounced clinical manifestations of menopausal syndrome. Patients in the control group had all clinical components and laboratory criteria of the metabolic syndrome, they also had greater limitations of joint function compared to patients of the main group. In patients with CTD pathogenetic mechanisms of development and progression of OA differ from the metabolic phenotype of OA.

Conclusion. The dysplastic phenotype of OA develops in the absence of metabolic syndrome and with less functional impairment than the metabolic phenotype. The metabolic phenotype of OA is associated with insulin resistance, more pronounced functional and psycho-emotional disturbances.

Slow-acting symptomatic drugs (SYSADOA) occupy one of the leading positions in the complex treatment of osteoarthritis (OA). These drugs have a symptomatic and structure-modifying effect, while they are well tolerated and rarely cause serious adverse reactions (AEs). This review examines the evidence base for the use of one of the most popular SYSADOAs, avocado-soybean unsaponifiable compounds (ASACs, Piascledine 300).

Objective: to provide the most complete analysis of clinical trials of ASACs in OA.

Patients and methods. We performed a search in English-language (PubMed) and Russian-language (eLIBRARY.ru) electronic libraries for publications on clinical studies of the efficacy and safety of ASACs in OA. Among the English-language publications were selected: 3 randomized controlled trials (RCTs) of ASACs and their symptomatic effect (n=587), 2 RCTs of the structure-modifying effect of ASACs (n=562), 1 RCT comparing the effect of ASACs and chondroitin sulfate (n=364), and 1 observational study of ASACs in real practice (n=4185). Among the Russian- language publications, 1 observational study of ASACs in real practice (n=6448) and 5 papers containing data from open clinical trials of ASACs (n=356) were found.

Results and discussion. According to the results of the presented studies, ASACs have proven efficacy in reducing the intensity of pain and dysfunction in knee OA. There are data confirming the structure-modifying effect of ASACs in OA of the hip joint (HJ). This drug is well tolerated: in RCTs, the incidence of AEs during ASACs and placebo usage was comparable. In observational studies (n=10 634), there were no serious AEs associated with the use of ASACs.

Conclusion. There is a robust evidence base for the expediency of the active use of ASACs in knee OA. Given the similarity of the pathogenesis of OA of different localizations, the data of individual successful studies and a favorable safety profile, the use of ASACs can also be considered as a component of the complex treatment of OA of the hip joint, hand joints and spine.

Objective: to evaluate the effect of the generic drug of zoledronic acid on bone mineral density (BMD) and markers of bone metabolism in patients with osteoporosis (OP), as well as possible long-term adverse reactions (AR) 12 months after drug administration.

Patients and methods. The study included 30 postmenopausal women with OP (mean age 64±8 years) who signed an informed consent of participance in clinical observation. Patients received a single dose of generic zoledronic acid (5 mg) as a 15-minute infusion. All patients additionally took calcium and vitamin D. The dynamics of BMD and bone metabolism markers, as well as the safety and tolerability of the drug, were evaluated. Fractures that might have occurred during follow-up should have been reported as ARs.

Results and discussion. During treatment with generic zoledronic acid, the increase in BMD in the lumbar region was 4.9% (p<0.0001), in the femoral neck –2.7% (p<0.01), and in the femur as a whole – 3.0% (p<0.0001). Positive dynamics (increase in BMD>2%) in the spine was detected in 26 (86.7%) patients, in the proximal femur – in 20 (66.7%) patients. There was a decrease in the intensity of pain in both the thoracic (by 62%; p=0.038) and lumbar (by 29%; p=0.022) spine. Three months after the administration of the drug, a decrease in the level of bone metabolism markers was revealed: CTX – by an average of 29.7%, and P1NP – by an average of 25.5%. ARs were post-dose reactions that occurred within the first 48 hours after drug infusion. Remote ARs, fractures of peripheral bones and vertebrae were not recorded.

Conclusion. The use of the generic drug of zoledronic acid has demonstrated its positive effect on BMD and markers of bone metabolism, as well as safety.

Objective: to study the practice of organizing and conducting telemedicine consultations (TMC) of a rheumatological profile, their effectiveness and the main problems that arise during the implementation of this technique.

Patients and methods. From June 2020 to December 2021, 102 rheumatological TMCs were performed at the «New Hospital» Medical Association in Yekaterinburg. Patients aged 18–82 years applied for TMC after a face-to-face examination and for the purpose of «pre-consultation». TMC included the following steps: familiarizing the doctor with previous medical reports and the results of examinations; video conference; preparation of final medical report. The Aibolit service and the «Medkarta» platform were used. After TMC, a survey of doctors and patients was conducted to identify the positive and negative aspects of this technique.

Results and discussion. Most of the patients who applied for TMC suffered from diseases that required regular monitoring of disease activity (rheumatoid arthritis, psoriatic arthritis, systemic connective tissue diseases), as well as fibromyalgia. Leading reasons for seeking medical advice: exacerbation of the disease or new symptoms onset, the need for laboratory and instrumental monitoring and correction of therapy. The vast majority of patients (90.2%) received answers to all questions and 9.8% – to most of the questions. Doctors had technical problems in 34 (33.3%) cases, including 11 (10.8%) cases when they had to switch to another method of communication.

Conclusion. TMK is a promising technique that can be useful and convenient for patients both now, during the COVID-19 pandemic, and in the future. Its main unresolved problems are the recognition of parity between TMK and face-to-face consultations and the improvement of technical conditions.

The article presents a description of a clinical case with a fatal outcome due to SARS-CoV-2 coronavirus-induced bilateral viral pneumonia with areas of pneumofibrosis, complicated by acute respiratory failure. The presence of systemic sclerosis in this patient aggravated the course of the disease and became one of the causes of death. Autopsy revealed signs of bilateral pneumonia with lesions in both lungs and areas of pneumofibrosis.

Histological examination revealed alveoli with rupture of interalveolar septa, areas of atelectasis, serous-purulent exudate with desquamated alveolocytes, places with organization of exudate, zones of pneumofibrosis. Scleroderma cardiosclerosis, linear necrosis of cardiomyocytes were present in the heart. There were signs of multiple organ failure – pulmonary edema, cerebral edema.

Ferritin is a complex protein composite (iron protein) that plays the role of the main intracellular iron depot in humans and animals, consisting of the protein apoferritin and the ferric atom in the composition of phosphate hydroxide. The reference value of ferritin in women is 200 μg/l, in men – 300 μg/l. Ferritin is a marker of total body iron stores, and low levels are specific for iron deficiency. Ferritin is also involved in immune processes and has both pro-inflammatory and immunosuppressive activity. Hyperferritinemia is a nonspecific symptom that occurs in a number of immunoinflammatory, infectious diseases, as well as during body iron stores overload. Hyperferritinemia is a criterion sign of macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis, systemic lupus erythematosus and Kawasaki disease, as well as a predictive biomarker of adult-onset Still's disease. High ferritin levels occur in catastrophic antiphospholipid syndrome, as well as in infectious pathologies such as septic shock and COVID-19, including multisystem inflammatory syndrome associated with COVID-19. Ferritin concentration is an important parameter for assessing the activity and prognosis of the disease, which allows a rational approach to the choice of therapy in these patients.

Classical serological markers of antiphospholipid syndrome (APS) are antibodies to cardiolipin, antibodies to β2-glycoprotein 1, and lupus anticoagulant. The utility of testing other antiphospholipid antibodies, not included in the classification criteria for improving the diagnosis of autoimmune thrombophilia continues to be debated. The review presents literature data on the study of antibodies to prothrombin and the phosphatidylserine/prothrombin complex in patients with systemic lupus erythematosus and APS.

Pain is one of the main symptoms and the most distressing manifestation of rheumatic diseases (RD). Currently, non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the symptomatic treatment of RD in real clinical practice, but the effectiveness and tolerability of their longterm use remain insufficiently studied. Many patients with RD require long-term use of NSAIDs. In this case, the presence of comorbid pathology and risk factors for the development of drug complications should be taken into consideration, so the choice of NSAIDs should be based primarily on considerations of patient safety. Aceclofenac (Aertal®) has a pronounced analgesic potential and a good safety profile, which allows us to recommend it for long-term use.

We present the review of clinical and experimental studies on the pathogenesis of neurorheumatological complications (NRC) in COVID-19. The influence of systemic hyperinflammation caused by impaired innate immunity on the functioning of the neurovascular endothelium and the bloodbrain barrier, activation of signaling pathways of innate immunity and parainfectious autoimmunity in the central nervous system were analyzed.

Hyperinflammation has been shown to contribute to the development of NRC in COVID-19. The potential therapeutic efficacy of drugs, including those based on chondroitin sulfate, which can be used for the prevention and treatment of NRC in COVID-19, is considered.

The review systematizes modern data indicating effective pain control and a significant improvement in the functional activity of patients suffering from osteoarthritis (OA) using pharmaceutical substances of chondroitin sulfate (CS) and glucosamine (GA). The effect of a combination of CS and GA on subclinical inflammation (low-grade inflammation) in the joints, slowing down the progression of OA, reducing cardiovascular risk, metabolic disorders, etc. are discussed. There are promising reports of a possible decrease in overall mortality and mortality from cardiovascular diseases during long-term therapy with symptomatic delayed-acting drugs (SYSADOA). A wide range of pleiotropic effects of CS and HA allows us to classify these drugs as geroprotectors and recommend their use not only in OA, but also in various comorbid conditions.