Aim – to study the clinical manifestations of rheumatoid arthritis (RA) and the spectrum of concomitant diseases, depending on the level of hepcidin in patients with high inflammatory activity. Material and methods. The analysis included 78 patients (48.9±15.5 years) with RA, disease duration of 108 [48; 204] months. All patients were diagnosed with high or medium inflammatory activity of the disease (DAS28-ESR (Disease Activity Score 28 with erythrocyte sedimentation rate detection – 5.2). Indicators of iron metabolism, levels of hepcidin and interleukin 6 were determined. Three subgroups of patients were identified: subgroup I – with serum hepcidin levels below the reference values (less than 40 pg/ml); subgroup II – with hepcidin levels within the reference values (40–120 pg/ml); subgroup III – patients with high hepcidin levels (more than 120 pg/ml). Results. It was found that in RA with high inflammatory activity, regardless of the hemoglobin level, disorders in iron metabolism were noted in 83% of cases. Reduced serum hepcidin levels were diagnosed in 40% of cases (subgroup I), on average, very high hepcidin values were detected in every second (n=34; subgroup III). The main clinical manifestations of RA, DAS28 activity and duration of the disease were comparable in all three subgroups. The largest number of concomitant diseases were diagnosed in RA patients with high levels of hepcidin. Chronic obstructive pulmonary disease (26%), endocrine pathology – 22% (diabetes mellitus, thyroid diseases, obesity), chronic kidney disease (21%) and cardiovascular disease (60%) were significantly more common (p<0.05). With iron deficiency, the most common pathology was gastrointestinal tract damage – 35% (erosive gastritis, peptic ulcer of the stomach and duodenum, etc.), the second most common was pathology of the cardiovascular system (32%). In the same subgroup, one in ten had a change of two classes of bDMARDs/tsDMARDs by the time of the study. Conclusion. The results of this study illustrate the need for further study of the pathogenetic pathways of iron metabolism disorders in order to form scientifically sound approaches to personalized treatment of a wide range of immunoinflammatory rheumatic diseases, including RA.

Anemia is still one of the most common comorbidities that affects the prognosis of the underlying disease and the quality of life of patients. Objective : to evaluate the value of serum hepcidin level determination for the differential diagnosis of anemia of chronic disease/inflammation (ACD) in patients with active rheumatoid arthritis (RA). Material and methods . The study included 47 patients with RA with anemia consecutively admitted to V.A. Nasonova Research Institute of Rheumatology for inpatient treatment. According to WHO recommendations, the criterion for anemia was a decrease in hemoglobin level ˂ 120 g/l in women and ˂ 130 g/l in men. The control group consisted of 29 patients without anemia. In all patients, the DAS28 index was determined, and clinical and biochemical blood parameters were examined: serum iron, total iron-binding capacity of serum, hepcidin, cytokines, including interleukin (IL) 6 and tumor necrosis factor α (TNFα). Results and discussion . Of 47 patients with active RA and anemia, only 13 (28%) were diagnosed with isolated ACD. Iron deficiency anemia (IDA) was found in 17 (36%), the remaining 17 patients had a mixed genesis of anemia (ACD + IDA). Patients with isolated ACD had a statistically significant higher level of hepcidin(120.3±56.1 pg/ml) compared to the control group (90.3±37.9 pg/ml) and to patients with RA + IDA. In isolated ACD, the levels of IL6, TNFα, rheumatoid factor and antibodies to cyclic citrullinated peptide were 2 times higher (p<0.05) than in RA with iron deficiency (both in IDA and in mixed genesis of anemia). Only in isolated ACD did the hepcidin level correlate with the IL6 concentrations (r=0.8); no such correlation was found in patients with IDA and anemia of mixed origin or in patients without anemia. No correlation with TNFα levels was found in any subgroup. Conclusion. Hepcidin levels are an informative indicator for the differential diagnosis of the type of anemia during active inflammation. In RA patients with ACD, the maximum hepcidin concentration in blood serum was determined, and in IDA it was found to be lower than the reference values. The importance of the hepcidin – IL6 axis and the lack of influence of the proinflammatory cytokine TNFα on iron metabolism were demonstrated. Keywords: hepcidin; anemia; difficult-to-treat patient; rheumatoid arthritis> ˂ 0.05) than in RA with iron deficiency (both in IDA and in mixed genesis of anemia). Only in isolated ACD did the hepcidin level correlate with the IL6 concentrations (r=0.8); no such correlation was found in patients with IDA and anemia of mixed origin or in patients without anemia. No correlation with TNFα levels was found in any subgroup. Conclusion . Hepcidin levels are an informative indicator for the differential diagnosis of the type of anemia during active inflammation. In RA patients with ACD, the maximum hepcidin concentration in blood serum was determined, and in IDA it was found to be lower than the reference values. The importance of the hepcidin – IL6 axis and the lack of influence of the proinflammatory cytokine TNFα on iron metabolism were demonstrated.

Gout is a chronic inflammatory arthropathy, caused by articular and periarticular sodium monourate (MUN) crystals deposition on the background of chronic hyperuricemia. Gout belongs to the group of autoinflammatory diseases characterized by activation of the innate immune system. In some cases, especially in women, with a long course of the disease and absence of adequate therapy, chronic arthritis is detected, which has little difference from that in rheumatoid arthritis (RA). At the same time, until recently, the combination of RA and gout was considered casuistry due to the inhibition of crystal formation by specific factors associated with RA, what is more mechanisms of inflammation development characteristic of these diseases are completely different. However, according to the latest data, the coexistence of these two diseases in one patient is possible, and the therapy of both, gout and RA (in some patients) can be successful when prescribing biological disease modifying antirheumatic drugs, in particular inhibitors of the interleukin 1 receptor (IL1r). The article presents a rare clinical case of chronic tophi gout in an elderly patient who was followed up for a long time with a diagnosis of RA, a significant improvement was achieved on therapy with the IL1r antagonist anakinra.

One of the main tasks of modern complex therapy of rheumatoid arthritis (RA) is to improve the quality of life of patients. To do this, it is necessary not only to achieve remission or low activity, but also to successfully control the main, most painful, manifestations of the disease. Therefore, when evaluating the results of RA treatment, the dynamics of not only standard indices (DAS28 (Disease Activity Score 28), CDAI (Clinical Disease Activity Index), SDAI (Simplified Disease Activity Index)), but also the so-called “patient reported outcomes” (PRO) – a patient’s global assessment of disease activity (PGA), pain, functional disorders and fatigue.This review examines the effect of one of the main classes of anti–rheumatic drugs - biological disease-modifying antirheumatic drugs (bDMARDs) on the PROs. The results of a series of randomized controlled trials are presented, in which changes in PROs were studied using various tumor necrosis factor α (TNF-α) inhibitors, abatacept T-lymphocyte co-stimulation inhibitor, rituximab CD20 inhibitor and interleukin (IL) 6 inhibitors.The use of bDMARDs in combination with methotrexate (MTX) provides a reduction in PGA and pain by 50-60%, functional disorders according to HAQ (Health Assessment Questionnaire) and fatigue according to FACIT-F (Functional Assessment of Chronic Illness Therapy – Fatigue) – by 15-30%. B DMARDs monotherapy (with the exception of the effect of tocilizumab on HAQ) does not exceed MTX monotherapy in its effect on PROs. Monotherapy with tocilizumab provides more favorable dynamics of PGA and pain than monotherapy with TNF-α inhibitors. An important advantage of IL-6 inhibitors is the rapid achievement of a clinical effect, which is noted already in the first 2 weeks after the first administration of the drug.

Несмотря на прогресс в изучении метаболизма железа, анемия хронического воспаления (АХВ) и дефицит железа по-прежнему остаются серьезными глобальными проблемами здравоохранения. При иммуновоспалительных ревматических заболеваниях (РЗ) наиболее частыми их вариантами являются железодефицитная анемия (ЖДА) как наиболее распространенный тип анемии, и АХВ, которая сама по себе может утяжелять течение основного заболевания за счет перегрузки железом тканей, дополнительной активации и поддержания активности воспаления. В течение последних лет широко обсуждается диагностическая и терапевтическая роль гепсидина как ключевого регулятора метаболизма железа. Изучение путей регуляции и синтеза гепсидина при иммуновоспалительных РЗ может иметь немаловажное значение для выявления патогенетических механизмов, лежащих в основе формирования резистентности к проводимой терапии, а также к появлению у пациентов тяжелой сопутствующей патологии, затрудняющей назначение адекватной терапии. Наиболее интересными с точки зрения перспективы дальнейшего изучения являются ось интерлейкин 6 – JAK2 – STAT3 и хроническая гипоксия, которая встречается при таких хронических состояниях, как сердечно-сосудистая патология, хроническая болезнь почек, интерстициальное поражение легких и др.

Increasing attention in rheumatology is today paid to the detection of diseases at the earliest possible (preclinical) stages, which can contribute to a more favorable response to therapy. The preclinical period of a systemic autoimmune reaction is assumed to be related to dysregulation of immune interactions with the synanthropic microflora. A sequencing method was used to study deviations in the diversity of the gut microflora in patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. However, a number of unresolved issues remain, since the emphasis has been on the cataloguing of the microorganisms present and on the identification of correlations between microbial species and diseases. The main difference in future microbiome research in patients with immune-mediated inflammatory diseases should be a closer examination of the functions of microbiota components, and not just their description. Long-term studies with the collection of intestinal microbiome samples are required at several time intervals: before disease-modifying antirheumatic drug therapy and during ineffective therapy. Such studies will contribute to the development of new diagnostic and therapeutic interventions. Until they are completed, it is untimely to recommend microbiome analysis as a diagnostic or prognostic tool for the management of rheumatic diseases in clinical practice.

Objective: to evaluate changes in T- and B-lymphocyte subpopulations at different stages of rheumatoid arthritis (RA).Patients and methods. The study included 53 patients with a definite RA diagnosis according to the 2010 ACR/EULAR criteria (mean age 54.2 [47; 62] years). Group 1 included 27 patients (25 women and 2 men) without history of synthetic disease modifying anti-rheumatic drugs (sDMARDs) intake, group 2 included 26 patients (22 women and 4 men) receiving sDMARDs (methotrexate or leflunomide). The control group consisted of 29 healthy volunteers (23 women and 6 men), the median age was 58.5 [53; 62] years. In all participants flow cytofluorometry according to the standard technique with immunophenotyping of T- and B-lymphocytes was performed.Results and discussion. Compared to controls, patients in group 1 who had not previously received sDMARDs showed a transient increase in "switched" memory B-cells, transient B-cells, and plasmablasts, which was not observed in patients of group 2 (on sDMARDs therapy). Patients with advanced RA showed a statistically significant decrease in the absolute and relative number of memory B-cells, the absolute and relative number of "switched" B-lymphocytes, as well as the number of plasmablasts and transient cells. In RA patients, a statistically significant rela tionship was established between the number of swollen joints and the level of plasmablasts (r=0.51), memory cells (r=0.54), and "switched" B-cells (r=0.41), p< 0,05 in all cases. There were no statistically significant changes in other subpopulations of B-lymphocytes and the profile of T-lymphocytes.Conclusion. Changes in the B-lymphocyte profile are characteristic of different stages of RA. At an early stage, there is an increase in the number of transient B-lymphocytes, plasmablasts and plasmocytes, and in the advanced stage, a decrease in the level of certain populations of B-lymphocytes, such as memory B-cells and "switched" B-lymphocytes. It can be assumed that the ineffectiveness of sDMARDs is associated with a change in the population composition of B-lymphocytes, which requires further study.

Objective : to evaluate changes in T- and B-lymphocyte subpopulations at different stages of rheumatoid arthritis (RA). Patients and methods . The study included 53 patients with a definite RA diagnosis according to the 2010 ACR/EULAR criteria (mean age 54.2 [47; 62] years). Group 1 included 27 patients (25 women and 2 men) without history of synthetic disease modifying anti-rheumatic drugs (sDMARDs) intake, group 2 included 26 patients (22 women and 4 men) receiving sDMARDs (methotrexate or leflunomide). The control group consisted of 29 healthy volunteers (23 women and 6 men), the median age was 58.5 [53; 62] years. In all participants flow cytofluorometry according to the standard technique with immunophenotyping of T- and B-lymphocytes was performed. Results and discussion . Compared to controls, patients in group 1 who had not previously received sDMARDs showed a transient increase in "switched" memory B-cells, transient B-cells, and plasmablasts, which was not observed in patients of group 2 (on sDMARDs therapy). Patients with advanced RA showed a statistically significant decrease in the absolute and relative number of memory B-cells, the absolute and relative number of "switched" B-lymphocytes, as well as the number of plasmablasts and transient cells. In RA patients, a statistically significant rela tionship was established between the number of swollen joints and the level of plasmablasts (r=0.51), memory cells (r=0.54), and "switched" B-cells (r=0.41), p< 0,05 in all cases. There were no statistically significant changes in other subpopulations of B-lymphocytes and the profile of T-lymphocytes. Conclusion . Changes in the B-lymphocyte profile are characteristic of different stages of RA. At an early stage, there is an increase in the number of transient B-lymphocytes, plasmablasts and plasmocytes, and in the advanced stage, a decrease in the level of certain populations of B-lymphocytes, such as memory B-cells and "switched" B-lymphocytes. It can be assumed that the ineffectiveness of sDMARDs is associated with a change in the population composition of B-lymphocytes, which requires further study.

The article discusses the difficulties of differential diagnosis of early arthritis and inflammatory bowel diseases with a predominant clinical picture of extraintestinal manifestations, in particular, articular syndrome. The clinical observation demonstrates features of the course of such conditions, a long diagnostic search and a wide list of diseases included in differential diagnostics range.

The effect of an inhibitor of interleukin-6 (IL-6) receptors on the state of the cardiovascular system in patients with rheumatoid arthritis remains poorly understood. Objective: to study the effect of therapy with an inhibitor of IL-6 receptors, tocilizumab (TCZ), on the dynamics of modifiable risk factors, total cardiovascular risk, and structural changes in the carotid arteries in patients with rheumatoid arthritis during a 12-month follow-up period. Material and methods . The study included 40 patients with active rheumatoid arthritis (33 women and 7 men) with ineffectiveness and/or intolerance to basic anti-inflammatory drugs (DMARDs); the median age was 55 (49; 64) years, the duration of the disease – 102 (48; 162) months; DAS28 – 6.2 (5.5; 6.7) points; all patients were seropositive for rheumatoid factor, 80% – for antibodies to cyclic citrullinated peptide. Patients received TCZ 8 mg/kg therapy every 4 weeks: 52% received TCZ monotherapy, 48% received combined TCZ therapy with DMARDs. All patients underwent an assessment of traditional risk factors, the total cardiovascular risk was calculated using the mSCORE, and atherosclerotic vascular damage was assessed by the detection of atherosclerotic plaques. Results. After 12 months of TCZ therapy, a decrease in disease activity was noted: remission was observed in 25 patients (64%) with rheumatoid arthritis, low disease activity – in 12 (31%); DAS28, HAQ, CRP and ESR concentrations decreased significantly. А high frequency of traditional risk factors was found in rheumatoid arthritis patients: dyslipidemia – 67%, arterial hypertension – 65%, overweight – 55%, burdened heredity for cardiovascular diseases (CVD) – 35%, smoking – 15%. Every third patient had a combination of three or more traditional risk factors. After 12 months of TCZ therapy, the frequency of traditional risk factors did not significantly change, there was an increase in BMI by 2%, an increase in the concentration of HDL-C in serum by 27%, a decrease in the atherogenic index by 28% (p<0.01). Moreover, an increase in the level of HDL-C by the finish was found in patients regardless of statin therapy. Changes in the concentration of other lipids during the observation, including during therapy with statins, were not observed. A negative correlation the dynamics of the levels of ∆HS and ∆CRP (R=−0.37; p<0.05), ∆HS of LDL and ∆CRP (R=−0.42; p<0.01) was found. A very high cardiovascular risk according to the SCORE scale was determined in 78% of patients, moderate – in 2%, and low – in 20% of patients. The distribution of patients by mSCORE value and level of cardiovascular risk were not documented after 12 months of TCZ therapy. No significant structural changes in carotid arteries in rheumatoid arthritis patients were revealed by the end of 12 months of TCZ therapy. Conclusion. After 12 months of TCZ therapy resulted in decreased rheumatoid arthritis activity, increased the level of HDL-C, atherogenic index, BMI; the frequency of traditional risk factors and the total cardiovascular risk did not change. Despite the very high risk of developing CVD associated with the inflammatory activity of rheumatoid arthritis, the accumulation of traditional risk factors and their combination, subclinical atherosclerotic vascular lesions, no significant structural changes in the carotid arteries were found in rheumatoid arthritis patients on TCZ therapy. Insufficient effectiveness of statin therapy was revealed.