According to modern views, chronic low-grade inflammation, the development of which is associated with the uncontrolled activation of both innate and acquired immunity, plays a fundamental role at all stages of the atherosclerotic process. The contribution of inflammation to the development of an atherosclerotic vascular lesion drew attention to the similarity of the mechanisms in the immunopathogenesis of atherosclerosis and the classic immunoinflammatory disease (IID) – rheumatoid arthritis (RA). Interleukin 1β (IL-1β), which plays an important role in the development of many acute and chronic IIDs, is of particular interest with regard to its implication in the pathogenesis of an atherosclerotic vascular lesion and as a promising therapeutic target. The atherosclerosis development mechanisms related to IL-1β determine the ability of cholesterol crystals and other proatherogenic factors to induce IL-1β synthesis due to NLRP3 inflammasome activation. There is strong evidence that inflammation plays a role in the development of atherosclerosis as a whole and that anti-inflammatory therapy has good prospects particularly in the randomized placebo-controlled trial (RPCT) CANTOS (Canakinumab ANti-inflammatory Thrombosis Outcomes Study) investigating the efficiency of treatment with canakinumab (Novartis International AG), an anti-IL-1β monoclonal antibodies, in patients with severe atherosclerotic vascular lesions as a new approach to secondary prevention of cardiovascular events. Methotrexate (MTX) has now been convincingly shown to be an effective drug (a gold standard) in not only controlling the inflammatory activity of RA, but also in significantly reducing the risks of cardiovascular catastrophes. This has served as a basis for planning the RPCT CIRT (The Cardiovascular Inflammation Reduction Trial) to evaluate the antiatherogenic effect of MTX in the general population of patients with coronary heart disease. The CANTOS results and the experience gained in rheumatology to determine the cardiovascular effects of innovative anti-inflammatory drugs are of great importance in improving the secondary prevention of atherosclerosis-related cardiovascular events.

The paper gives recommendations for the drug therapy of axial spondyloarthritides, which have been developed by the Spondyloarthritis Study Group of Experts. The recommendations describe the patient management tactic in the most common clinical situations, which is aimed at maximizing the efficacy and safety of treatment.

To enhance the efficacy and safety of nonsteroidal anti-inflammatory drugs (NSAIDs), a class of essential medications used to treat acute and chronic pain, is an important and urgent task. For its solution, in 2015 Russian experts provided an NSAID selection algorithm based on the assessment of risk factors (RFs) for drug-induced complications and on the prescription of drugs with the least negative effect on the gastrointestinal tract and cardiovascular system. The PRINCIPLE project was implemented to test the effectiveness of this algorithm.

Subjects and methods. A study group consisted of 439 patients (65% were women and 35% – men; their mean age was 51.3±14.4 years) with severe musculoskeletal pain, who were prescribed NSAIDs by using the above algorithm. The majority of patients were noted to have RFs: gastrointestinal and cardiovascular ones in 62 and 88% of the patients, respectively. Given the RF, eight NSAIDs were used; these were aceclofenac, diclofenac, ibuprofen, ketoprofen, meloxicam, naproxen, nimesulide, and celecoxib, the latter being prescribed most commonly (in 57.4% of cases). NSAID was used in combination with proton pump inhibitors in 30.2% of the patients. The follow-up period was 28 days. The investigators evaluated the efficacy of therapy (pain changes on a 10-point numeric rating scale (NRS)) and the development of adverse events (AE).

Results and discussion. Pain was completely relieved in the overwhelming majority (94.9%) of patients. There were no significant differences in the efficacy of different NSAIDs according to NRS scores. The number of AE was minimal and did not differ between different NSAIDs, with the exception of a higher frequency of dyspepsia caused by diclofenac (15.7%). There were no serious complications or therapy discontinuation because of AE.

Conclusion. The use of the NSAID selection algorithm allows for effective and relatively safe therapy with these drugs in real clinical practice.

Psoriasis (Ps) and psoriatic arthritis (PsA) are, in addition to skin and osteoarticular lesions, accompanied by a variety of comorbidities, primarily cardiovascular diseases (CVDs), which contributes to shorter life expectancy by on an average of 5–7 years. There are scarce data on the prevalence and pattern of CVDs in a Russian cohort of patients with severe forms of Ps and PsA. Obtaining such information can contribute to the elaboration of programs for screening and prevention of CVDs in this patient group.

Objective: to study the prevalence and pattern of CVDs in a hospital cohort of patients with severe forms of Ps and PsA.

Subjects and methods. Medical records were retrospectively analyzed in 890 patients with severe forms of Ps (mean age, 51.9±11.6 years; mean Ps duration, 11.6±0.6 years); who had been treated at the Branch of the V.G. Korolenko Clinic, Moscow Research and Practical Center of Dermatovenereology and Cosmetology, in 2010 to 2015. The Psoriasis Area and Severity Index (PASI) averaged 49.4±0.5. The frequency of PsA was assessed by the code L40.5; that of SVDs was determined by the registered diagnoses in accordance with the codes of the International Classification of Diseases, 10th edition (ICD-10): hypertension (ICD-10 code I10–I15), coronary heart disease (CHD) (I20–I25), atherosclerosis (I70), and cerebrovascular disorders (I65–I66).

Results and discussion. PsA was identified in 303 (34%) patients. There were a total of 516 (59%) patients with CVDs. Hypertension, CHD, atherosclerosis, and cerebrovascular disorders were more frequently recorded in patients with PsA than in those with PsA without arthritis.

Conclusion. CVDs are recorded in more than half of the hospital cohort patients with severe forms of Ps. CVDs are more frequently recorded in PsA than in Ps without arthritis. Hypertension among the SVDs is a leader in its frequency in both groups; more than half of the patients were found to have CHD and atherosclerosis; cerebrovascular disorders were less common.

The authors have previously conducted studies that demonstrate the increased level of cytogenetic disturbances in patients with Ixodes tick-borne borreliosis (ITB). The severity of arthritis associated with ITB (AITB) is also ascertained to depend on whether the patient has certain HLA-DRB1 alleles.

Objective: to assess the association between HLA-DRB1 gene polymorphism and cytogenetic changes in the peripheral blood T lymphocytes of patients with AITB.

Subjects and methods. 146 patients with AITB, 100 clinically healthy convalescents with ITB (CITB), and a control group of 98 healthy blood donors (HBDs) without a history of tick-borne infections were examined using cytogenetic (micronucleus analysis of cytokinesis-blocked peripheral blood T lymphocytes) and molecular genetic (PCR analysis of HLA-DRB1 gene polymorphism) methods.

Results and discussion. The frequency of cytokinesis-blocked lymphocytes with micronuclei in the AITB group was significantly higher than that in the CITB and HBD groups (p<0.01) with the exception of the results obtained in the subgroup of patients with AITB who had the DRB1*10 allele (p>0.05). The highest levels of lymphocytes with micronuclei were observed in AITB patients with the DRB1*17(03), *01, and *04 alleles as compared to those in the CITB and HBD groups (p<0.001). The CITB group showed the most significant increase in the detection rate of lymphocytes with micronuclei in people with the DRB1*01, DRB1*04, or *17(03) alleles. At the same time, there were no significant differences in the number of lymphocytes with micronuclei in the HBD group, depending on the HLA-DRB1 gene alleles (p>0.05). Thus, the patients with AITB had the highest frequency of cytogenetic disorders with the exception of individuals with the DRB1*10 allele.

Objective: to investigate the prevalence of traditional risk factors (RFs) and to determine a 10-year risk for type 2 (T2) diabetes mellitus (DM), by using the Finnish Diabetes Risk Score (FINDRISC) in patients with rheumatoid arthritis (RA).

Subjects and methods. The investigation enrolled 418 RA patients without a history of DM. The median age of the participants was 54 [41; 63] years; the median disease duration was 6 [2; 12] years. Most of the patients were positive for rheumatoid factor (75.6%) and anti-cyclic citrullinated peptide antibodies (77.3%) and had moderate and high RA activity (81.8%). Glucocorticoids (GCs), disease-modifying anti-rheumatic drugs, and biological agents were used in 42.1, 66.7, and 23.9% of the patients, respectively. FINDRISC was used to assess the risk of T2DM. A control group consisted of 100 gender- and age-matched individuals without inflammatory joint diseases or DM.

Results and discussion. The most common modifiable traditional RFs in RA were abdominal obesity (AO) (63.6%), overweight (50.7%), and lack of physical activity (70.3%); the non-modifiable RF was age older than 45 years (69.1%). The RA and control groups showed the similar prevalence of RFs, except for AO that was more common in the absence of inflammatory joint diseases (75.0%) (p = 0.03). The number of RFs did not differ in RA patients (median RFs, 4 [2; 5]) and control individuals (4 [3; 5]) (p = 0.23). The moderate risk of developing T2DM in the ensuing ten years was 20.1 and 18.0% in RA patients and control individuals, respectively; the high risk was in 19.6 and 24.0% and the very high risk was in 2.7 and 2.0%, respectively (p > 0.05 in all cases). In RA, there was a weak correlation between the number of RFs and DAS28 (r = 0.10; p = 0.05), RFs and HAQ (r = 0.19; p < 0.01). Examinations detected fasting hyperglycemia (glucose ≥6.1 mmol/l) in 3.8% of the RA patients with a low/slightly increased risk for T2DM and in 16.1% of those with its moderate, high, and very high risks (p < 0.01). The use of GCs did not affect the number of RFs, the distribution of groups at risk for DM, and the frequency of hyperglycemia. These findings can lead to the conclusion that the risk of developing T2DM in RA is associated with a high frequency of modifiable traditional RFs, such as obesity and lack of physical activity. FINDRISC is a simple method to identify RA patients who need lifestyle monitoring and modification, as well as an additional examination to rule out latent T2DM.

Involvement of the aorta and heart valves in ankylosing spondylitis (AS) is a manifestation of the systemic inflammatory process. Data on the frequency, clinical significance, and evolution of these manifestations are controversial.

Objective: to estimate the time course of echocardiographic (EchoCG) changes in the aorta and heart valves from the results of a prospective follow-up study of patients with AS.

Subjects and methods. In 2008 to 2015, the V.A. Nasonova Research Institute of Rheumatology followed up 45 patients (35 men and 10 women) with documented AS that was consistent with the modified New York criteria and the original EchoCG changes in the aorta and heart valves. All the patients underwent transthoracic echocardiography at baseline and after 1–5 years. At baseline, there was aortic root dilatation (>37 mm) in 15 patients, thickening of the aortic walls and aortic valve (AV) cusps in 21 and 32 patients, respectively, as well as thickening of the mitral valve (MV) cusps in 15, and valve prostheses in 5 patients (2 had AV and MV prostheses). Aortic regurgitation (AR) was recorded in 19 patients (grades 1–2 AR in 15 patients and grades 3–4 in 4 patients); grades 1–2 mitral regurgitation (MR) was seen in 20 patients. Ten patients had subaortic pectinate thickening (SPT) in the aortomitral junction area. Of the 45 patients, 16 took biological agents (BA); 29 received traditional therapy, including 14 patients who used nonsteroidal anti-inflammatory drugs, 11 and 4 patients had sulfasalazine and methotrexate, respectively.

Results and discussion.Repeated examinations revealed negative changes in 27 (60%) of the 45 patients. Progressive aortic dilatation (1 to 6 mm) was found in 12 (80%) of the 15 patients; dilatation appeared during follow-up in 2 patients. Fourteen patients were noted to have negative valve changes: the emergence of cusp thickening in the valves (that in AV and MV in 9 and 4 patients, respectively; both in 1 patient). Four patients underwent valve replacement: 3 and 1 patients underwent AV and MV replacements, respectively. Ten of the 19 patients were observed to have AR progression by 2 grades in 2 (10.5%) patients and by one grade in 8 (42.0%) patients. MR progression by one grade was noted in 6 (30.0%) of the 20 people. A negative correlation was found between BA therapy and aortic dilation progression (r = -0.329; p = 0.03). SPT appeared in 3 patients. Of the 10 patients who had a baseline SPT, its reduction (8 to 3.5 mm) was seen in one patient; complete regression was identified in two patients; all received BAs. Thus, pathological changes in the aorta and heart valves in AS are progressive in most patients. SPT may regress, which reflects apparently a reduction in the severity of active inflammation of the aortic root. Active anti-inflammatory treatment may play a protective role in the progression of aortic dilatation.

Objective: to assess the psychometric properties (reliability, sensitivity, and validity) of a Russian-language version of the VEINES-QOL/Sym questionnaire in patients with rheumatic diseases and lower extremity chronic venous diseases.

Subjects and methods. The investigation enrolled 89 patients (66 (74%) women and 23 (26%) men) (their mean age was 46.3±13.4 years) with rheumatic diseases. The majority (n=62 (70%)) of patients were recorded to have a history of one case of venous thrombosis of the lower extremity; the others (n=27 (30%)) had more than one case of thrombosis. To calculate the scores the VEINES-QOL/Sym questionnaire, a standard method proposed by its authors was used. The patients filled out the VEINES-QOL/Sym questionnaire thrice: on inclusion, at 2 weeks, and at 6 months.

Results and discussion. The internal consistency (Cronbach’s α coefficient) of VEINES-QOL and VEINES-Sym was equal to 0.973 and 0.975, respectively, which reflects the high level of reliability. The coefficient κ varied from 0.825 to 1, which indicates good reproducibility (p < 0.001). The correlation coefficients of VEINES-QOL and VEINES-Sym with the physical component of SF36 were 0.59 and 0.42, and those with its psychological component were 0.42 and 0.35, respectively (p<0.05). The correlation coefficients of VEINES-QOL and VEINES-Sym with general health assessment on the visual analogue scale were -0.41 and -0.36, with a pain intensity of -0.56 and -0.46, respectively (p<0.05). The moderate relationships of VEINES-QOL and VEINES-Sym to the above parameters, as well as to the SF36 physical and psychological components suggest that the questionnaire is able to display quality of life in patients with rheumatic diseases and lower extremity venous diseases. The sensitivity of the VEINES-QOL/Sym questionnaire was assessed after its completion, at baseline, and at 6 months. According to the presence or absence of positive postthrombotic changes, as evidenced by duplex ultrasound scanning (DUSS), all the patients were divided into two groups. Calculation of a 6-month change in VEINES-QOL scores revealed that Group 1 with positive DUSS changes showed better quality of life (ΔVEINES-QOL=0.95 [-2.8; 6.7]); at the same time, Group 2 with no or negative DUSS changes displayed worse quality of life (ΔVEINES-QOL=-1.71 [5.7; 3.27]; p = 0.06); this suggests that the questionnaire can be used for assessing the quality of life in patients with lower extremity venous diseases over time. Thus, the VEINES/Qol-Sym questionnaire is a reliable and valid tool. It can be used to assess quality of life over time in patients with rheumatic diseases and lower extremity chronic venous diseases. The investigation confirmed the good psychometric properties of the VEINES/Qol-Sym questionnaire.

Objective: to investigate the incidence of acute rheumatic fever (ARF), chronic rheumatic heart disease (CRHD), musculoskeletal diseases (MSD), and connective tissue diseases in the pediatric and adult populations of the Arkhangelsk Region (AR) in comparison with the data on Russia and the North-Western Federal District (NWFD) in 2010–2015.

Subjects and methods. The total and primary incidence rates of ARF, CRHD, and MSD were analyzed in the pediatric and adult populations of these regions in 2010–2015.

Results and discussion. Among the adult population of AR, the total incidence of ARF was low (7 cases in 2010 and none in 2015), which is comparable with the data in the whole of Russia. No recurrences of ARF were registered in the AR. Among the adult population of AR, the total incidence of CRHD fell by 28% in 2010 to 2015. The similar trend was also observed in the whole of Russia. Patients newly diagnosed with CRHD decreased by 65% in the AR. There was a 14% increase in the total incidence of MSD among the adult population of AR and an 11% decrease in its primary incidence. Since 2010, the total incidence of rheumatoid arthritis (RA), osteoarthritis, spondylopathies (SP), osteoporosis (OP), and systemic connective tissue diseases rose in the AR. There were 22 and 140% increases in the incidence of RA and SP, respectively; the number of reactive arthritis cases decreased by 17.2% in the adults and increased by 7% in the children. This trend in the adults is seen of the whole of Russia (an 8% decrease), although the latter in the AR is not comparable to the All-Russian measures. In the AR, the incidence of OP remains low (50 and 73 per 100,000 population in 2010 and 2015, respectively); this is noted to increase by 46% in the past 5 years; the similar trend was observed in both the whole of Russia and NWFD (7.8 and 8.3%, respectively).

Systemic lupus erythematosus (SLE) is an autoimmune disease with various organs and systems involved in the pathological process, with an unpredictable course, a risk for life-threatening conditions, and an onset from childhood through adolescence in 10–20% of cases. The onset of SLE prior to adult age affects its clinical manifestations, course, and prognosis. Based on the data available in the literature, the paper analyzes the features of the onset and clinical presentations of SLE in children and adolescents and discusses the aspects of verifying its diagnosis, by taking into account the need to use early effective personalized therapy and to improve prognosis.

The need for further improvement of treatments for Takayasu’s arteritis (TA), the progress in understanding the mechanisms of the disease, and the introduction of biological agents (BA) in rheumatology practice have created preconditions for developing a new TA pharmacotherapy using BA associated with interleukin 6 (IL-6) inhibition. The authors describe their two own cases of tocilizumab (TCZ) use for complicated TA. They analyze the results of TCZ treatment by the data of preliminary trials in 115 patients with TA, which have been published in 30 literature sources, as well as the results of Phase III double-blind, randomized placebo-controlled trials (RPCTs) of the safety and efficacy of TCZ in 18 patients with refractory TA. In one case with a long history of complicated TA, the control of TA activity and the reduction in the dose of glucocorticoids due to TCZ use contributed to the favorable course of pregnancy and labor. In the other case with the onset of TA and focal pulmonary tuberculosis (TB) treated with anti-TB drugs during TCZ monotherapy for 6 months could control TA and achieve TB cure. Preliminary trials showed that TCZ treatment-induced remission or improvement was observed in 85% of patients with TA, including that with a refractory course. RPCTs indicated that the relapse-free survival after 6-month maintenance treatment with TCZ was higher than that in the placebo group (51 and 23%, respectively); but the differences failed to reach statistical significance (p = 0.0596). Due to the fact that a recurrence of TA can occur in patients treated with TCZ, it is appropriate to combine this drug with cytostatic drugs, methotrexate in particular. The use of IL-6 inhibitors should be considered as a potentially effective and relatively safe innovative (off-label) treatment for refractory TA in patients with intolerance or contraindications to standard therapy, which requires further larger randomized clinical trials. Since now there is no universal imaging method that could provide comprehensive information on the status of vessels in TA; the standardization of future clinical trials of BAs requires the improvement of methods for evaluating the efficiency of treatment for TA; moreover, monitoring of disease activity should include a comprehensive assessment of clinical data, current laboratory biomarkers, and instrumental imaging techniques, primarily non-invasive ones.

Total joint replacement (TJR) in the presence of severe joint degradation and arthralgias in patients with rheumatic diseases (RDs) is one of the effective ways to improve the functional status of patients and their quality of life. In recent years, there has been an increase in the number of such knee and hip replacements worldwide. Despite advances in medicine in the 21st century, up to 5% of TJRs culminate in early complications, in which there are irreversible joint changes that cause joint functional loss and persistent pain and, in 2–3% of cases, require early re-revision surgery.

Subjects and methods. The investigation included 2142 patients with rheumatoid arthritis (RA) and osteoarthritis (OA) who underwent knee or hip joint replacement (KJR or HJR) at the V.A. Nasonova Research Institute of Rheumatology during the period 1998 to 2016: HJR in 1177 patients and KJR in 965. The patients with RA had 467 HJRs and 651 KJRs (a total of 1118 operations). A comparison group consisted of patients with OA who underwent
710 HJRs and 314 KJRs (a total of 1024 operations). Postoperative surgical complications, such as superficial or deep suppuration, joint dislocation, periprosthetic fractures, sciatic and/or peroneal neuropathies, aseptic instability of endoprosthesis components, and complications of wound and ligamentous apparatus, were considered within 2 years after surgery

Results and discussion. Overall, the frequency of local complications after HJR and KJR was comparable and amounted to 7.22 and 7.25%, respectively (p=0.83), but their pattern greatly differed: there were a larger number of periprosthetic fractures after HJR than after KJR (3.48% and 0.93%; p <0.001). After KJR as compared to HJR, there were a greater number of infectious complications (1.66 and 0.27%; p <0.001) and a longer postoperative wound healing (1.87 and 0.42%; p <0.001). Comparison of the frequency of local complications revealed that there is a significant increase in patients with RA (29%) compared with those with OA (5.21%; p=0.001). The pattern of local complications was characterized by significant differences only in the frequency of periprosthetic fractures (p=0.028) and poor postoperative wound healing (p=0.019), which was higher than that in patients with RA. There was no statistically significant difference in the frequency of local complications after KJR in patients with RA and those with OA. Thus, surgical treatment of patients with RA requires a special approach that includes the competent perioperative medical management of a patient and the careful handling of the bone and surrounding tissues during surgery.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are an important component of a multimodal pain management program in patients with rheumatic diseases in the perioperative period. NSAIDs have comprehensive analgesic, antiinflammatory, and antipyretic effects associated with blockade of the enzyme cyclooxygenase-2 and suppression of the synthesis of prostaglandins, one of the main mediators of pain and inflammation, which are synthesized in response to surgical tissue injury. NSAIDs can ease the suffering of patients in the pre- and postoperative periods and reduce the need for opioid analgesics and the frequency of adverse events (AE) caused by the latter. The choice of NSAIDs is largely determined by the risk of AE: gastrointestinal, cardiovascular and postoperative bleeding. The paper considers whether different NSAIDs can be chosen for patients with joint diseases during surgical treatment in terms of their efficacy and safety.

The current ideas of gout include both the traditional metabolic theory of disorders of purine metabolism and environmental exposure and the involvement of immunoinflammatory factors in the pathological process. Inflammation is a hallmark of an acute tissue reaction to monosodium urate the crystals in gout and to calcium pyrophosphate crystals in pseudogout. The crystals interact with the membranes of plasma cells, with the activation of NLRP3, the proteolytic cleavage of pro-interleukin 1β, and the secretion of mature interleukin-1β that modulates a sequence of events leading to the activation of endothelial cells and neutrophils, which is also preceded by fatty degeneration of the liver. This review details recent data on the pathogenetic mechanisms that serve as predictors of metabolic changes and nonalcoholic fatty liver disease in patients with gout.

The review deals with the problem of generalized osteoporosis (OP) in psoriatic arthritis (PsA). Works published in the past 15 years were sought in the Medline using the keywords «psoriatic arthritis», «osteoporosis», and «osteoporosisassociated fractures» (fragility fractures, low-energy fractures, and osteoporotic fractures). The paper includes the data of studies on the frequency of OP and fractures, the risk factors of OP, and the impact of drug therapy on bone status in patients with PsA.

The paper considers discussion ideas about the possible causes of medicine uncertainty that arose in the era of digital technologies and information flooding.