The importance of comorbid infections in rheumatology has recently increased substantially, particularly due to the introduction of biological agents into clinical practice. One of the ways to solve the above problem is to investigate and actively use different vaccines. The paper deals with the issues concerning the use of vaccines against influenza and pneumococcal infections in rheumatic patients. It discusses the safety and immunogenicity of vaccination in preventing respiratory infections as the most common cause of an adverse outcome in rheumatic diseases. Main areas for future investigations of the considered problem are shown.

 

Systemic lupus erythematosus (SLE) with its onset in childhood or adolescence is a significant problem in the practice of pediatricians and rheumatologists due to diagnostic difficulties, clinical features, and the greater likelihood of unfavorable prognosis. About 20% of SLE patients fall ill at the age of 18 years. Only 13% of patients with juvenile-onset SLE have a drug-free remission in adulthood and have a lower quality of life than population controls. The paper discusses the latest international guidelines for the diagnosis, monitoring, and treatment of SLE in children and adolescents, which were published in 2017, with comments based on the data available in the literature and on practical experiences in managing these patients.

 

Recent demographic changes caused by labor migration and by the larger number of retirement-aged people, as well as unstable economic conditions are the reason for analyzing the incidence of osteoarthritis (OA) in the adult population of the Russian Federation in the light of changing socioeconomic factors. Objective: to analyze the incidence of OA in the regions of the Russian Federation in terms of key socioeconomic factors. Material and methods. Trends in OA prevalence and incidence were retrospectively analyzed using the data of annual statistical reports of the Ministry of Health of Russia (Form No. 12) in the period 2011–2016. The above parameters were studied among three population cohorts: adult, able-bodied, and retirement-aged (pensioners) people. Data on the execution of consolidated budgets of the regions of the Russian Federation, territorial compulsory health insurance funds (TCHIFs) were analyzed to identify substantial socioeconomic factors influencing the trends in statistical parameters. The findings were subjected to a comparative analysis of these parameters for Russia as a whole, 85 regions, and 8 federal districts. Results and discussion. During the period from 2011 to 2016, the prevalence of OA in Russia increased from 32.2 per 1,000 population in 2011 to 35.7 in 2016. The highest prevalence of OA is observed among the retirement-aged population and averages 33.2% of the number of registered patients per the total population in this age group during 6-year follow-ups. The maximum prevalence is seen in the retirement-aged population (70.4 per 1,000 corresponding age population; which is more than 3.8 times greater than that in the able-bodied one). There is a steady increase in the prevalence and incidence of OA in the population of Russia as a whole. According to official statistics, patients with OA make up one quarter of all patients with musculoskeletal system diseases and OA is detected in 4% of the entire adult population. Over 20 years, the number of patients with OA increased by 260%. The investigation has shown that the population’s income growth is associated with lower incidence and prevalence rates among pensioners. During 6 years, there is a decline in budget funding for health care in 30 regions of Russia. The share of expenditures in the consolidated regional budgets has been established to be directly associated with the incidence and morbidity of OA. There was an average 183% increase in the expenditures of TCHIFs in Russia. The expenditures of TCHIFs in the regions were directly related to the higher incidence of OA among adults and pensioners, but were unassociated with those among the able-bodied population.

Objective: to analyze the levels of CD3+, CD3+CD4+, CD3+CD8+, and CD3-CD56+ T lymphocytes, FoxP3+ regulatory T cells (T_reg), and CD19+ B lymphocytes in patients with early and advanced rheumatoid arthritis (RA). Subjects and methods. The investigation enrolled 45 patients previously untreated with methotrexate (MTX-naive) who had early RA and 15 patients who had advanced RA. Immunofluorescence staining and multicolor flow cytometry assays were used to estimate the percentage and absolute (abs) counts of CD3+, CD3+CD4+, CD3+CD8+, CD3-CD16+CD56+, CD19+, T_reg (FoxP3+CD25+; surface CD152+; intracellular CD152+; FoxP3+CD127; CD25+CD127-; FoxP3+ICOS+; FoxP3+CD154+; and FoxP3+CD274+. Results and discussion. The patients with early RA were found to have a lower percentage of FoxP3+CD25+ cells and lower percentages and abs counts of FoxP3+ ICOS+ cells, FoxP3+CD154+ cells, and FoxP3+ CD274+ T cells than healthy donors (p<0.05 in all cases). The patients with advanced RA were also recorded to have a lower percentage of FoxP3+CD25+ cells and lower percentages and abs contents of FoxP3+ ICOS+ cells, FoxP3+CD154+ cells, and FoxP3+ CD274+ T cells (p><0.05 in all cases). The patients with advanced RA compared to those with early RA had a higher content of CD4+ lymphocytes (50.7 [44.4; 53.1] and 45.0 [38.0; 49.2]) and lower percentages of CD25+CD127- T lymphocytes (5.0 [4.0; 5.7] and 6.5 [5.1; 7.9] respectively; p><0.05 in all cases). Conclusion. Patients with RA (with the early or advanced stage of the disease) show a decrease in both the counts and functional activity of Treg. The patients with advanced RA compared with those with early RA showed an increase in CD4+ lymphocyte counts and a decrease in CD25+CD127- cell levels, which suggests that there are more pronounced impairments in Treg homeostasis in advanced RA. Keywords: early rheumatoid arthritis; T lymphocytes; B lymphocytes; regulatory T cells><0.05 in all cases). The patients with advanced RA were also recorded to have a lower percentage of FoxP3+CD25+ cells and lower percentages and abs contents of FoxP3+ ICOS+ cells, FoxP3+CD154+ cells, and FoxP3+ CD274+ T cells (p<0.05 in all cases). The patients with advanced RA compared to those with early RA had a higher content of CD4+ lymphocytes (50.7 [44.4; 53.1] and 45.0 [38.0; 49.2]) and lower percentages of CD25+CD127- T lymphocytes (5.0 [4.0; 5.7] and 6.5 [5.1; 7.9] respectively; p><0.05 in all cases). Conclusion. Patients with RA (with the early or advanced stage of the disease) show a decrease in both the counts and functional activity of Treg. The patients with advanced RA compared with those with early RA showed an increase in CD4+ lymphocyte counts and a decrease in CD25+CD127- cell levels, which suggests that there are more pronounced impairments in Treg homeostasis in advanced RA. Keywords: early rheumatoid arthritis; T lymphocytes; B lymphocytes; regulatory T cells><0.05 in all cases). The patients with advanced RA compared to those with early RA had a higher content of CD4+ lymphocytes (50.7 [44.4; 53.1] and 45.0 [38.0; 49.2]) and lower percentages of CD25+CD127- T lymphocytes (5.0 [4.0; 5.7] and 6.5 [5.1; 7.9] respectively; p<0.05 in all cases). Conclusion. Patients with RA (with the early or advanced stage of the disease) show a decrease in both the counts and functional activity of Treg. The patients with advanced RA compared with those with early RA showed an increase in CD4+ lymphocyte counts and a decrease in CD25+CD127- cell levels, which suggests that there are more pronounced impairments in Treg homeostasis in advanced RA. Keywords: early rheumatoid arthritis; T lymphocytes; B lymphocytes; regulatory T cells><0.05 in all cases). Conclusion. Patients with RA (with the early or advanced stage of the disease) show a decrease in both the counts and functional activity of T_reg. The patients with advanced RA compared with those with early RA showed an increase in CD4+ lymphocyte counts and a decrease in CD25+CD127- cell levels, which suggests that there are more pronounced impairments in T_reg homeostasis in advanced RA.

 

Strontium ranelate (SR) that has a proven efficacy in reducing the risk of fractures and in increasing bone mineral density is currently recommended as a second choice drug for the treatment of severe osteoporosis (OP) in postmenopausal women and elderly men. Subjects and methods. In 2014–2015, a survey within the framework of the MARC program (The Use of Antiosteoporotic Drugs in Real Clinical Practice) was conducted in 1799 OP patients aged 25 to 92 years, who had been treated for this disease for at least one year. Among the respondents, there were 1696 people aged 50 years and older (mean age, 64±7 years; disease duration, 2.7±2.4 years) (86% women and 14% men) who were the subjects of this survey. Adherence to performed antiosteoporotic therapy was evaluated within the last 12 months before the survey by the following parameters: which drug had been taken; the number of packages used, treatment gaps and compliance with the treatment regimen. Results and discussion. The survey of the patients included in the study showed that 19% of them had received SR at any time over the course of the disease, and 8% had taken the drug within the year preceding the survey. Thus, SR remains a popular drug in real clinical practice for the treatment of severe OP in patients with no history of coronary heart disease, uncontrolled hypertension, cerebrovascular diseases, peripheral artery disease, and a predisposition to thrombosis and thromboembolism.

Objective: to investigate the safety and immunogenicity of 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with systemic lupus erythematosus (SLE). Subjects and methods. The investigation enrolled 30 patients with a reliable diagnosis of SLE; of them there were 27 women and 3 men at the age of 19 to 62 years. The disease duration ranged from 9 months to 20 years. At the time of inclusion in the investigation, the disease activity was high in 2 patients, moderate in 3, and low in 20; five patients were in remission. During a year before vaccination, pneumonia was detected in 5 (16.7%) of the 30 patients; there were a total of 18 episodes of various respiratory and ENT infections. The patients were examined at baseline and at 1, 3 and 12 months after vaccination. Standard clinical and laboratory studies and a detailed blood immunological analysis were carried out at visits. The levels of IgG antibodies to capsular polysaccharide pneumococcus were determined during each visit. Twenty-nine patients received glucocorticoids (GCs) at a dose of 5–30 mg/day; 24 – hydroxychloroquine; 14 – cytostatics (CS); 10 – biological agents (BAs) (5 – rituximab, 5 – belimumab). A single dose of 0.5 ml of PPV-23 (Pneumo 23, Aventis) was subcutaneously injected into the upper outer arm. Vaccination was done during the ongoing therapy with GC/CS and belimumab, as well as at least 1 month before the first (next) administration and/or 4.5–5 months after the last rituximab infusion. Results and discussion. 60% of patients were observed to have mild and moderate standard local vaccine reactions; 1 (3.3%) patient had a local hyperergic reaction eliminated within 7 days of the local application of antihistamines and GCs. During the follow-up, there was no SLE exacerbation significantly associated with the vaccination performed. No new autoimmune phenomena were found in any of the cases. A year after vaccination, a significant (2-fold or more) increase in anti-pneumococcal antibody levels remained in 19 (63.3%) patients (respondents); 36.7% of patients were nonrespondents. Among the patients who received a BA, the non-responders were significantly more than among those who did not take the drug (7 (70%) and 4 (20%), respectively) (p = 0.01). When treated with rituximab and belimumab, the number of non-respondents was comparable (4 and 3, respectively). The immunogenicity of PPV-23 was independent of the degree of SLE activity: the vaccine response was absent in 1 out of the 5 patients with high (n = 2) and medium (n = 3) SLE activities, as well as in 10 out of the 25 patients with low disease activity and remission. There was no development of considerable adverse reactions after vaccination in patients with high and medium SLE activity. The overall clinical efficiency of vaccination was 93.3%. Conclusion. Thus, PPV-23 shows a good tolerability and a sufficient immunogenicity in patients with SLE. There is a need for further investigations conducted in large samples of patients during long-term follow-ups in order to more fully evaluate the clinical efficacy, tolerability, and immunogenicity of PPV-23.

The response rate to therapy for rheumatoid arthritis (RA) rarely exceeds 60%. Mental disorders (MDs) of the anxiety-depressive spectrum (ADS) and cognitive impairment (CI) substantially affect the evaluation of the efficiency of RA therapy. Adequate psychopharmacotherapy is one of the possible approaches to optimizing the treatment of RA. The factors influencing the efficiency of RA therapy with standard disease-modifying antirheumatic drugs (DMARDs) and biological agents (BAs) in combination with adequate psychopharmacotherapy have not been previously identified. Objective: to determine the predictors of response to therapy in patients with RA receiving DMARDs and BAs with or without adequate psychopharmacotherapy for ADS disorders. Subjects and methods. The investigation included 128 patients (13% men and 87% women) with a reliable diagnosis of RA. At baseline, 75.1% of patients received DMARDs; 7.8% – BAs. ADS disorders were detected in 123 (96.1%) patients. Psychopharmacotherapy was offered to all the patients with MDs; 52 patients agreed to treatment and 71 refused. The following therapeutic groups were identified according to the performed therapy: 1) DMARDs (n = 39); 2) DMARDs + psychopharmacotherapy (n = 43); 3) DMARDs + BAs (n = 32); 4) DMARDs + BAs + psychopharmacotherapy (n = 9). The changes of MDs symptoms and the outcomes of RA were assessed in 83 (67.5%) patients at five-year follow-up. The efficiency of RA therapy was evaluated with DAS28 (EULAR criteria). Predictors of response to therapy were determined using linear regression modeling. Results and discussion. At 5 years, 22 (26.5%) and 37 (44.6%) patients were recorded to show good and moderate responses to therapy, respectively; 24 (28.9%) patients were non-respondents. The linear regression model included 14 factors (p<0.001). The high values of DAS28 (β=0.258) at the inclusion; belonging to therapeutic groups 2 (β=0.267), 3 (β=0.235), and 4 (β=0.210), the absence of diabetes mellitus (β=-0.230), and experience in using glucocorticoids (β=-0.230) were associated with a high likelihood of response to therapy; high body mass index (β=-0.200) and long RA duration (β=-0,181), a high level of rheumatoid factor (β=-0.176), a history of myocardial infarction (β=-0.153), schizotypic disorder (β=-0.132), and extra-articular manifestations of RA (β=-0.106), and older age (β=-0.102) were related to a low probability of response. The area under the ROC curve for the model was 0.99 (p><0.001). Conclusion. BA therapy and psychopharmacotherapy, along with younger age, shorter duration and high activity of RA, a low level of rheumatoid factor, lower body mass index, the absence of diabetes mellitus, myocardial infarction, and extra-articular manifestations of RA in the history, schizotypic disorder, and experience in using glucocorticoids are associated with a greater likelihood of a good and moderate treatment response. Keywords: rheumatoid arthritis; mental disorders; disease-modifying antirheumatic drugs; biological agents; efficiency of therapy; predictors; psychopharmacotherapy; therapy adherence><0.001). The high values of DAS28 (β=0.258) at the inclusion; belonging to therapeutic groups 2 (β=0.267), 3 (β=0.235), and 4 (β=0.210), the absence of diabetes mellitus (β=-0.230), and experience in using glucocorticoids (β=-0.230) were associated with a high likelihood of response to therapy; high body mass index (β=-0.200) and long RA duration (β=-0,181), a high level of rheumatoid factor (β=-0.176), a history of myocardial infarction (β=-0.153), schizotypic disorder (β=-0.132), and extra-articular manifestations of RA (β=-0.106), and older age (β=-0.102) were related to a low probability of response. The area under the ROC curve for the model was 0.99 (p<0.001). Conclusion. BA therapy and psychopharmacotherapy, along with younger age, shorter duration and high activity of RA, a low level of rheumatoid factor, lower body mass index, the absence of diabetes mellitus, myocardial infarction, and extra-articular manifestations of RA in the history, schizotypic disorder, and experience in using glucocorticoids are associated with a greater likelihood of a good and moderate treatment response. Keywords: rheumatoid arthritis; mental disorders; disease-modifying antirheumatic drugs; biological agents; efficiency of therapy; predictors; psychopharmacotherapy; therapy adherence><0.001). Conclusion. BA therapy and psychopharmacotherapy, along with younger age, shorter duration and high activity of RA, a low level of rheumatoid factor, lower body mass index, the absence of diabetes mellitus, myocardial infarction, and extra-articular manifestations of RA in the history, schizotypic disorder, and experience in using glucocorticoids are associated with a greater likelihood of a good and moderate treatment response.

Rheumatoid arthritis (RA) is a disease with a high cardiovascular risk. The results of works on the impact of antirheumatic therapy on carotid artery (CA) intima-media thickness (IMT) are contradictory. Objective: to assess the time course of changes in CA IMT and CA atherosclerosis (CAA) in patients with early RA during treatment to target at a 18-month follow-up. Subjects and methods. The investigation enrolled patients with early RA (disease duration of less than 12 months), who had not previously taken disease-modifying antirheumatic drugs and glucocorticoids. Duplex scanning (DS) of the CA was performed with IMT measurement at baseline and at 18 months after treatment. Vascular atherosclerotic lesion was recorded when atherosclerotic plaque (ASP) was detected. Starting methotrexate (MTX) monotherapy was prescribed to all the patients, when it showed an insufficient effect at 3 months, a biological agent (BA), such as a tumor necrosis factor-α inhibitor or abatacept, was added. RA remission was noted in 31 (42%) patients at 18 months of treatment. Results and discussion. The investigation included 74 patients with early RA; whose median (Me) age was 56 years, all the patients had moderate or high disease activity (Me DAS28-ESR, 5.4). At baseline, there was increased CA IMT in 51.4% of cases and CAA in 55.4%. At 18 months of treatment, there were no significant IMT changes. New CA ASPs were recorded in 8 (24.2%) patients who had no CAA at the time of inclusion in the investigation (p < 0.05). Nineteen (46.3%) patients were recorded to have the progression that had been identified when including CAA as a considerable increase in the number of ASPs (p < 0.05). The risk of CAA progression was correlated inversely with the mean 18-month level of high-density lipoprotein cholesterol (HDL-Cmean) and directly with the mean concentration of C-reactive protein (CRPmean). There was no significant correlation between HDL-Cmean and CRPmean. The changes of CAA were unassociated with the value of DAS28-ESR, the achievement of RA remission, and antirheumatic therapy (MTX monotherapy, MTX + BA). Conclusion. CAA shows progress in patients with early RA despite they are treated to target. DAS28-ESR remission in RA and ongoing RA treatment option had no substantial impact on the course of CAA. HDL-Cmean and CRPmean are independent risk factors for progression of CAA.

The absence of a current emergency care system for rheumatic patients makes the solution of this problem relevant. Objective: to create and test a health care system for patients with acute articular syndrome (AAS) and to analyze the distribution of patients according to the profile of hospitalization. Subjects and methods. The practice of providing medical care to patients with AAS was studied using the materials of the I.I. Dzhanelidze Research Institute of Emergency Care (RI of EC) in 2008 to 2015. The causes of hospital admissions were analyzed by taking into account the verified nosological diagnosis. Results and discussion. The incidence of AAS in the general flow of patients referred for hospitalization was analyzed; the most frequent causes of AAS were determined. Trends in the referral of rheumatic patients to inpatient and outpatient treatment were analyzed separately. The decrease in the proportion of rheumatic patients in need of inpatient treatment from 76.7 to 50.8% during the study allows optimization of the costs of the health care system. Conclusion. The presented concept of providing medical care to patients with AAS has proven its effectiveness as a result of its testing at the RI of EC from 2008 to the present time. This concept can be recommended for its introduction in other subjects of the Russian Federation.

The currently used methods for evaluating the progression of structural damages in early axial spondyloarthritis (axSpA) are little suitable to real practice since they require specially trained radiologists and increase a patient's exposure to radiation due to the need for radiography of three regions of the axial skeleton. In addition, the first radiological bone changes in the sacroiliac joints (SIJ) appear only many years after the onset of the disease, the overlying spine areas are involved in the pathological process. Objective: to develop a method for evaluating the radiographic progression of sacroiliitis (SI) in early axSpA for real clinical practice. Subjects and methods. The investigation enrolled patients from the early spondyloarthritis cohort (ESAC) formed at the V.A. Nasonova Research Institute of Rheumatology. The current ESAC comprised 164 patients; the analysis included 68 patients who had been followed up for at least 2 years and had plain pelvic bone films at the inclusion in the cohort and at 2-year follow-up. To evaluate disease progression, the investigators used the sum of radiographic SI stages in the left and right SIJs (the summary stage of radiographic SI (ssrSI), which was calculated at baseline and at 2-year follow-up. A formula for determining the rate of radiographic progression was derived. Results and discussion. At baseline and at 2-year follow-up, the median ssrSI difference (ΔssrSI) in 68 patients was 0 [0; 1.0]. During the study period, almost 60% of the patients had no progression of ssrSI, i.e. ΔssrSI was 0 in these patients, 1 and 2 scores in 12 (18%) and 13 (19%) patients, respectively, and there were singly cases, in which this figure was equal to 3, 4 and 7. The mean value of ssrSI was 3.5±1.6 at baseline and increased by 0.8, reaching 4.3±1.5 at 2 years (p = 0.006). Before included into the investigation, the patients had a progression rate of 1.75 during 1 year, which decreased to 0.4 per year in the active follow-up period. At the time of inclusion in the study, 40 (58.8%) of the 68 patients had ankylosing spondylitis (AS), and at 2 years their number increased to 51 (75.0%); i.e. 11 (39%) patients were observed to have progression of non-radiographic axSpA to AS. Conclusion. The proposed procedure to calculate ssrSI is easily feasible in real practice; it fails to lead to additional radiation exposure, is economically feasible, and allows one to monitor the rate of progression of axSpA in the early stage of the disease.

In accordance with international and Russian guidelines for the management of patients with rheumatoid arthritis (RA), after its diagnosis, a synthetic disease-modifying antirheumatic drug is prescribed, among these drugs, methotrexate is anchor and, when the latter is impossible to use, leflunomide is commonly administered. Objective: to evaluate the efficacy and safety of a leflunomide generic (Elafra) during a multicenter follow-up. Subjects and methods. The investigation enrolled 347 patients aged over 18 years who met the 2010 ACR/EULAR criteria for RA, had its duration of less and more than 2 years, signed informed consent, and followed up in 29 centers of Russia. Elafra was prescribed at a saturating dose of 100 mg for the first 3 days, then 20 mg/day. There might be a temporary two-fold reduction in the dose when adverse events (AE) occurred. The patients were examined before and 4, 12 and 24 weeks after beginning leflunomide treatment. The treatment efficiency was evaluated with DAS28 and CDAI and by the physician global assessment. Results and discussion. The patients were divided into two groups: 1) 125 patients with RA of less than 2 years’ duration and 2) 222 patients with RA of more than 2 years’ duration. The mean age of patients in Group 1 was 48.7±12.9 years; that in Group 2 was 52.5±11.95 years; the mean disease duration was 11.9±7.8 and 90.99±54.28 months, respectively. During 24-week treatment, there was a highly significant decrease in all assessed clinical, laboratory parameters and indices of RA activity in both groups. At 4 weeks of treatment, the effect was observed in 91.8% of the patients in Group 1 and in 84.6% in Group 2, whereas at 12 weeks the effect was noted in almost all patients (99.1% and 96.9% in Groups 1 and 2, respectively). The highest rate of AE during Elafra therapy was recorded in the early periods: at 4 weeks, AE were noted in 6.5% of the patients in Group 1 and in 9.9% in Group 2, without needing to discontinue the drug. Treatment continuation decreased the rate of AE. Because of its intolerance, Elafra was discontinued due to in one case in Group 1 (diarrhea at 24 weeks of treatment) and in 6 cases in Group 2 (at 12 and 24 weeks of treatment). Conclusion. Treatment with leflunomide (Elafra) leads to the rapid development of its effect in early and late RA in most patients and is characterized by a good tolerability.

Pulmonary arterial hypertension (PAH) is a complex, multidisciplinary problem of modern medicine. The basis for the disease is a microcirculatory lesion in the vessels, which leads to a decrease in their blood flow, to increased pulmonary vascular resistance and, as an outcome, right ventricular failure, and death. PAH may also be associated with systemic connective tissue diseases (SCTDs), in particular with systemic sclerosis (SS), as one of the manifestations of the disease. As well as idiopathic pulmonary hypertension, PAH-SCTDs is an orphan disease: according to the data of the V.A. Nasonova Research Institute of Rheumatology, the incidence of PAH is 5.2% in SS, 0.3% in systemic lupus erythematosus, and 7.4% in mixed connective tissue disease. Low prevalence is responsible for late diagnosis, which is always associated with a poor therapy response and poor prognosis. The purpose of the lecture is to acquaint rheumatologists with the possibilities of diagnosis and treatment of this rare, but prognostic severe manifestation of SCTDs.

Одна из актуальных и развивающихся проблем современной медицинской науки – поражение сердечно-сосудистой системы, обусловленное атеросклеротическим поражением сосудов, у больных с иммуновоспалительными ревматическими заболеваниями (РЗ). Ревматоидный артрит (РА) – заболевание с известно высоким кардиоваскулярным риском. Установлено, что основная причина высокой преждевременной смертности при РА связана с сердечно-сосудистыми осложнениями, обусловленными ускоренным прогрессированием атеросклероза. Распространенность субклинических и клинических проявлений атеросклероза при РА составляет 35–59%. Наиболее часто ССО развиваются у больных РА с низким или умеренным кардиоваскулярным риском, но с высокой клинико-иммунологической активностью болезни. Привлекает внимание схожесть механизмов иммунопатогенеза классических РЗ и хронического low-grade воспаления при атеросклерозе. По современным представлениям, хроническое воспаление, развитие которого связывают с неконтролируемой активацией как врожденного, так и приобретенного иммунитета, играет фундаментальную роль на всех стадиях аутоиммунных РЗ и атеросклеротического процесса. Среди многочисленных «иммунных» клеток и медиаторов, участвующих в иммунопатогенезе как РА, так и атеросклероза, важное место занимают моноциты-макрофаги и цитокины, продуцируемые ими. Дисбаланс между M1- и M2-фенотипами макрофагов рассматривается в качестве одной из причин развития РА. Определена важная роль М1-макрофагов, продуцирующих два основных «провоспалительных» цитокина – интерлейкин 6 (ИЛ6) и ИЛ23, – в поддержании ревматоидного воспаления. Проводятся поиски возможных механизмов возникновения дизрегуляции М1/М2-макрофагов при воспалении. Изучение ключевого патогенетического фактора в развитии аутоиммунного и атеросклеротического воспаления – активированных моноцитов-макрофагов – не только углубит знания о патогенезе хронического воспаления, но и позволит расширить представления о патогенетическом и предиктивном значении «клеточных» маркеров и перевести на качественно новый уровень раннюю диагностику атеросклеротического поражения при РА.

Calprotectin (CP) belongs to the S100 leukocyte protein family, consists of two calcium-binding protein molecules, S100A8 and S100A9 (MRP8/14, calgranulin A/B). MRP8/14 is the main intracellular protein of neutrophil granulocytes and monocytes, which exerts a proinflammatory effect on phagocytes, endothelial cells in vitro and favors the development of the inflammatory process in vivo; it is an important mediator of many regulatory functions, such as chemotaxis; activation of neutrophil degranulation and phagocytosis; inhibition of immunoglobulin synthesis, cell proliferation and differentiation. CP is currently considered as a potential acute-phase marker in many inflammatory and autoimmune diseases. In rheumatoid arthritis (RA), CP maintains chronic inflammation, by activating the endothelium and increasing the migration of neutrophils into the inflamed synovial fluid. A number of studies have demonstrated the role of CP in monitoring RA activity, detecting subclinical inflammation, and predicting disease exacerbations. CP is of great importance in monitoring the efficiency of RA therapy with disease-modifying antirheumatic drugs and biological agents. The value of CP in spondyloarthritis (SpA) is ambiguous: on the one hand, this marker is highly expressed in the synovial tissue of patients with SpA and correlates with the level of acute-phase reactants; on the other hand, its correlation with disease activity indices is very contradictory and requires further clarification. By and large, CP is a promising laboratory marker of great clinical significance.

The review analyzes the foreign and Russian literature published in the past 30 years and devoted to the diagnosis and treatment of coxitis in ankylosing spondylitis (AS). The results of previous works have revealed the high rate of hip joint injury (HJI) in AS, but it is still unclear which diagnostic technique is the most sensitive for the early detection of coxitis. The latter has been shown to serve as one of the predictors of early disability in patients. The most studied treatment for coxitis is now HJI endoprosthesis, for which indications and contraindications have been clearly developed, while the question of drug therapy remains open.

The review gives an update on adult-onset Still’s disease: on its causes, the specific features of its pathogenesis, diagnosis, clinical presentations (with identification of subtypes), and treatment with consideration for the nature of the course of the disease and life-threatening complications.

The paper describes a case of a 36-year-old man with finger joint and bone damage that occurred a year and a half after severe frostbite.

When rheumatoid arthritis (RA) is treated with rituximab (RTM), there may be various adverse events, among which progressive multifocal leukoencephalopathy (PML) occupies a special place. The disease is caused by activation of opportunistic viral (JC-virus) infection in the presence of weakened cellular immunity, which leads to massive demyelination of brain structures. The paper describes a clinical case of using RTM in a female patient with RA with systemic manifestations. This treatment was effective during two years, but multifocal brain damage characteristic of PML developed after the last (fourth) cycle of infusions. Differential diagnosis with other diseases accompanied by similar brain changes allowed the authors to regard PML as the most likely diagnosis in this patient despite the negative result of determining JC virus DNA in blood and spinal fluid. The chosen therapy policy (a reduced dose of glucocorticoids, the use of a serotonin reuptake inhibitor, the antidepressant mirtazapine, and therapeutic plasmapheresis) with regard for presumed PML the patient has been proven to be effective and provided a modest positive trend. 

The symptoms similar to those detected in rheumatic diseases in patients infected with human immunodeficiency virus (HIV) are due to various pathogenetic mechanisms (immune cell imbalance, antibody production, etc.). The occurrence of rheumatic symptoms and syndromes in HIV infection can lead to diagnostic errors and wrong treatment policy (use of immunosuppressive therapy instead of high-dose antiretroviral therapy). The paper describes two clinical cases of HIV infection in the stage of acquired immunodeficiency syndrome (AIDS) in young and middle-aged women, who were misdiagnosed rheumatic diseases at baseline. In the first case, a 34-year-old woman was suspected to have systemic lupus erythematosus before HIV infection diagnosis, whereas the leading clinical syndrome was nephropathy (nephrotic syndrome, hypertension). In the other case, in a 62-year-old woman, the manifestations of the advanced stage of HIV infection at baseline were regarded as mixed connective tissue disease, while the greatest similarity was found in the concurrence of Sjö gren’s syndrome. The paper discusses the reasons for diagnostic difficulties in each case and the specific features of organ damages in comparison with the data available in the literature.

 

The paper discusses the appearance of unusual – paradoxical – adverse reactions that occur as a result of treatment of rheumatic diseases with biological agents.