The paper considers the historical and geographical aspects of Behcet’s disease (BD). As is known, the geographical distribution of this disease is associated with the ancient caravan route called the Silk Road: it was in these areas along which the latter once ran there have been predominantly cases of BD so far. There are discrepancies in the literature regarding whether the Silk Road was across the North Caucasus, along the coast of the Caspian Sea in particular. In support of this conjecture, there is interesting evidence: stone-cutting images that have been retained on the houses of the Dagestani settlement of Kubachi. All give an answer why the natives of the North Caucasus constitute one-fourth of the total number of BD patients followed up at the V.A. Nasonova Research Institute of Rheumatology 

The start of the new millennium is marked by a substantial progress in the development of rheumatology: pathogenesis of many rheumatic diseases (RDs) was more deeply studied; their diagnostic criteria validated; disease activity indices worked out; the concepts of remission and exacerbation introduced; much attention has been given to the investigations of quality of life in patients. The possibility of pharmacotherapy for immunoinflammatory RDs was extended by the advent of biological agents (BA). The treatment strategy for RDs was also changed. The treat-to-target concept was put forth for rheumatoid arthritis in 2010 and for ankylosing spondylitis later. The project of treat-to-target concept in systemic lupus erythematous (SLE) was launched on the initiative of the world’s leading rheumatologists in January 2013. The result of their work is the treat-to-target-in-SLE recommendations published in 2014 and formulated as 4 basic principles and 11 general recommendations. The purpose of this publication is to provide general characteristics of the basic provisions of the principles and recommendations with commentaries of leading experts discussing characteristics of SLE in the Russian Federation and some debatable and unsolved problems. 

Objective: to assess trends in disease activity, functional status, and radiographic changes, and their relationships in patients with early rheumatoid arthritis (RA).
Subjects and methods. The investigation enrolled 200 patients with early RA included in the RADIKAL (Early arthritis: diagnosis, outcomes, criteria, active treatment) program in the period 2003 to 2007. The duration of the disease at inclusion was <2 years. RA diagnosis fulfilled the 1987 American College of Rheumatology (ACR) criteria. Rheumatoid factor was found in 67.5% of the patients and anti-cyclic citrullinated peptide antibodies were detected in 57%. 86.5% of patients were female; median age was 49 [40; 58] years. The patients received traditional disease-modifying antirheumatic drugs and biological agents (24%). Monitoring was made according to the tight control principle. Determination of main clinical and laboratory parameters, DAS28, HAQ disability index (DI) and functional class, as well as hands and feet X-ray were done every year.
Results. There was stabilization of RA activity and functional status over 5 years. Median DAS28 at inclusion was 5.1 [4.49; 5.85], that after 1, 2, 3, 4, and 5 years was 3.05 [2.25; 4.43], 3.04 [2.07; 4.23], 2.55 [1.86; 3.74], 2.48 [1.78; 3.77], and 3.12 [1.86; 4.32], respectively. Median HAQ DI was 1.125 [0.625; 1.75], 0.5 [0.125; 1.0], 0.5 [0; 1.0], 0.5 [0; 1.0], 0.5 [0; 1.0], and 0.75 [0.125; 1.125], respectively. During the entire follow-up period, there was a stable positive correlation between DAS28 and HAQ DI (r = 0.61–0.77). Despite reductions in DAS28 and HAQ DI, destruction progressed. Joint erosions were seen in 16% of the patients at inclusion; and in 27.5, 38.5, 49.5, 58, and 73% at 1-, 2-, 3-, 4-, and 5-year of follow-up, respectively.
Conclusion. The found positive correlation between DAS28 and HAQ DI suggests that lower RA activity has a favorable impact on the functional status of patients. However, irreversible structural joint changes continue to develop in the presence of persistent RA course, which can cause a higher HAQ score that may be noted after 5 years of follow-up. 

Most patients with early rheumatoid arthritis (RA) have a high or very high cardiovascular risk (CVR) before therapy with disease-modifying antirheumatic drugs (DMARDs).
Objective: to evaluate the impact of antirheumatic therapy performed in accordance with the Treat-to-Target strategy on the progression of atherosclerosis and CVR in patients with early RA. 
Subjects and methods. This investigation enrolled 74 patients (72% women; median age, 56 years) with early RA having moderate to high activity (median DAS28, 5.6) who had not previously received DMARDs and glucocorticoids (GCs). All patients were anticyclic citrullinated peptide antibody-positive and 87% of the patients were rheumatoid factor-positive. All patients received methotrexate (MT) subcutaneously with dose escalation up to 25–30 mg/week, in case of its inefficiency at 3 months a biological agent (BA) was added. After 6 months, 39% of the patients achieved remission; 19% had low; 35 and 7% had moderate and high disease activity, respectively. The majority (n = 20 (69%)) who achieved remission received MT monotherapy; 9 (31%) – MT + BA whereas among the patients who did not achieve remission 15 (33%) and 30 (67%) respectively. At baseline and after 6 months of treatment, traditional CVR factors were assessed in all patients, by determining the total coronary risk by the SCORE scale, including that modified by EULAR (mSCORE), carotid artery atherosclerosis (CAA) by duplex scanning data, coronary calcification (CC) by multislice spiral computed tomography and by estimating the degree of CVR.
Results and discussion. The rates of hypertension, overweight, abdominal obesity, low activity, smoking, and type 2 diabetes mellitus did not change significantly after 6 months. There were increases in the levels of total cholesterol by 7% (p < 0.05), low-density lipoprotein cholesterol by 9% (p<0.01), high-density lipoprotein cholesterol by 26% (p < 0.005), and body mass index (BMI) by 1% (p < 0.01) and a decrease in the atherogenic index (p<0.005). The change in blood lipid spectrum concentrations was correlated positively with trends in BMI (p < 0.05) and negatively with those in the levels of inflammatory markers (C-reactive protein, erythrocyte sedimentation rate; p < 0.05). Following 6 months, there was a rise in the total CVR according to the SCORE and mSCORE scales (p < 0.005). The elevations in the rates of CAA from 59 to 72% and CC from 42 to 47% resulted in an increase in the proportion of persons with very high CVR from 67 to 76%; however, the differences failed to attain statistical significance. There was a similar increase in the rates of CAA and CC in the groups of patients receiving monotherapy with MT and MT + BA. In the patients who failed to achieve remission in RA, the rise in the rate of CAA was 18% higher than in those who did (3%) (p = 0.05). A significant progression in CAA was noted in the persons who failed to achieve remission and received no statins (p = 0.05) while the rate of CAA remained unchanged among those who took statins and achieved remission in RA.
Thus, the preliminary data of the REMARCA study have shown that the progression of atherosclerosis can be delayed in patients with early RA if they achieve remission during antirheumatic therapy and simultaneously use statins regularly, which may be further associated with a reduction in CVR.

Objective: to investigate the impact of specific features of the course of ankylosing spondylitis (AS), sociodemographic factors, and therapy on quality of life (QL) in patients with this disease.
Subjects and methods. The results of studying QL (with the SF-36 questionnaire) in 90 adult patients with AS versus
45 healthy individuals (a control group) were presented. Within 6 months before study inclusion, 30 patients with AS received only nonsteroidal anti-inflammatory drugs (NSAIDs); 27 – NSAIDs + sulfasalazine (SULF), 15 – NSAIDs + infliximab (INF); 18 (20%) patients were not systematically treated and were excluded from the study. A control group comprised 45 apparently healthy volunteers (32 men and 13 women); both groups were matched for gender and age.
Results and discussion. The patients with AS were found to have lower physical and psychological QL scores than the controls (p < 0.001). In those with AS, QL worsened as the inflammatory disease activity, functional limitations, articular manifestations and enthesitis increased. Coxitis detected in 76.7% of the patients had a negative effect on rolephysical functioning. The sociodemographic factors were not found to have a statistically significant influence on QL in the patients with AS. The QL scores were higher in the patients taking INF in combination with NSAIDs. Evaluation of the impact of performed drug therapy on QL in the patients receiving SULF versus the controls revealed statistically significant worse scores in all the scales of the SF-36 questionnaire (p < 0.001). In the patients who had NSAIDs only, the QL scores were also worse than those in the control group (p < 0.001). According to the data of the SF-36 questionnaire, a number of QL scores in the patients receiving INF + NSAIDs proved to be similar in the apparently healthy individuals. 

Thus, the patients with AS have considerably lower physical and psychological QL scores than the healthy people. QL worsens as the inflammatory activity of AS and functional limitations increase. No influence of sociodemographic factors on QL was found in the patients with AS. Therapy with INF in combination with NSAIDs ensured higher QL in these patients than did other treatments. 

Objective: to study the actual intake of vitamins and calcium and their provision in rheumatoid arthritis (RA) in the Middle Urals.
Subjects and methods. The case-control method was used to form 150 pairs of RA patients aged 55.31±11.3 years. Their actual nutrition was studied from the frequency of food intake for a month, by applying a questionnaire. Based on the obtained food consumption data, the authors calculated the daily intake of vitamins A, B2, C, E, β-carotene, and calcium. The plasma levels of these factors were measured in 40% of the random patient sample and in 68 (45%) control persons. A complete clinical examination included the evaluation of patients' general health and articular status, inflammatory activity assessment with DAS28, laboratory tests (general blood and urine analyses, estimation of the levels of transaminases, creatinine, electrolytes, C-reactive protein, and rheumatoid factor), and instrumental examination, involving electrocardiography and joint X-ray. 
Results and discussion. The study demonstrated that actual nutrition was depleted of vitamins A, C, and B2 in the patients with RA as compared to the controls. Inadequate provision of vitamin C, β-carotene, riboflavin, and calcium was found in RA. The inconsistency between the consumption of vitamins C, B2, and β-carotene and their plasma levels could suggest increased demands for these nutrients in RA. The findings should undergo detailed studies; first of all, this concerns the comparison of intake of the nutrients and their provision with the most important clinical characteristics of RA, such as duration, progression, activity, X-ray stage, and the presence of rheumatoid factor. The knowledge of these matters could, in our opinion, improve the results of therapy and prognosis in RA.

Objective: to identify factors associated with low quality of life (QL) in patients with gout.
Subjects and methods. The investigation enrolled 175 patients (153 men and 22 women) with a definite diagnosis of gout. Their mean age was 48.0±12.3 years; median disease duration – 5.7 [3.0; 12.3] years; the annual number of arthritis attacks – 3 [1; 5]; and the mean serum level of uric acid (UA) – 510±120 μmol/l. 31.4% of the patients received allopurinol; 40.5% had chronic arthritis; 36.5% – subcutaneous tophi, 23% – coronary heart disease (CHD); 76% – hypertension; 15.4% – type 2 diabetes mellitus (DM); 10.2% – chronic kidney disease (CKD) at a glomerular filtration rate of <60 ml/min; 56% – obesity; 5.1% – chronic heart failure (СHF); 9.1% – history of vascular catastrophes. Pearson’s and Spearman’s correlation analyses were made to reveal correlations between QL measures according to the EQ-5D and SF-36v1 questionnaires, HAQ functional status (FS), and the clinical characteristics of the disease, as well as comorbidities. Multiple regression analysis was used to identify factors worsening QL.
Results and discussion. Negative correlations were found between SF-36 QL measures and age, disease duration, serum UA level, presence of chronic arthritis and tophi, use of allopurinol, diuretics, alcohol, as well as hypertension, CHD, obesity, vascular catastrophes, CKD, and CHF. The multiple regression analysis established a direct association between HAQ FS worsening and female gender, elderly age, number of inflamed joints and frequency of arthritis attacks; the coefficient of multiple determination (R2) was 0.41. EQ QL correlated inversely with age, number of inflamed joints, frequency of arthritis attacks, intake of diuretics and obesity (R2 = 0.33). The reduction in the SF-36 physical health component correlated with increases in age, number of inflamed joints, and frequency of arthritis attacks, presence of CKD (R2 = 0.3); a weak association was noted between worsening mental health component and female gender, increased number of inflamed joints, and vascular catastrophes (R2 = 0.1).
Conclusion. Decreased QL in gout is independently associated with higher number of inflamed joints, frequency of arthritis attacks, elderly age, female gender, and comorbidities (CKD, obesity, vascular catastrophes).

Objective: to assess the significance of noninvasive estimation of pulmonary artery pressure (PAP) using Doppler echocardiography (echoCG) as compared to invasive measurements of this parameter in patients with systemic connective tissue diseases (SCTD).
Subjects and methods. The invasively measured hemodynamic parameters versus those estimated at echoCG were analyzed. The analysis included 156 paired studies of 61 patients with pulmonary hypertension (PH) in the presence of SCTD and 26 patients, in whom PH was not verified by catheterization. Forty-five patients were found to have PH; PH was caused by left heart involvement in 7 patients and by hypoxemia in 9. 
Results and discussion. Systolic PAP (SPAP) measured by echoCG averaged 72.4±33.7 mm Hg and that by right heart catheterization did 63.3±25.1 mm Hg. The correlation of the values of this measure, which were obtained by the two methods, was highly significant (r = 0.83; p < 0.00001). Right atrial pressure (RAP) measured by echoCG and catheterization was 8.4±4.1 and 6.7±5.2 mm Hg, respectively. The echoCG and catheterization RAP correlation was highly significant (r = 0.57; p < 0.0001). 

Despite the high correlation coefficients, echoCG failed to detect higher SPAP in 7 patients with PH verified by catheterization; EchoCG could not detect higher SPAP; false-positive results were absent. EchoCG demonstrated good sensitivity (94%) and specificity (100%) for a threshold SPAP of 40.1 mm Hg (the area under the curve was 0.99 (p < 0.0001) with 95% CI 0.98–1.01. The echoCG determination of RAP by the existing methods showed good sensitivity (79%) and specificity (69%) for its threshold of 5 mm Hg (the area under the curve was 0.79 (p < 0.0001) with 95% CI 0.70–0.95. 

The patients with low level of mean PAP (PAPmean) measured by catheterization showed a difference of > 10 mm Hg as compared with the echoCG levels in 5% of the cases; > 20 mm Hg discrepancy was not noted. In patients with high PAPmean, the differences of > 10 and > 20 mm Hg were observed in 28.9 and 34.2% of the cases, respectively.
Analysis of the Bland–Altman agreement showed deviations of +8.22 mm Hg for SPAP (95% CI 6.6–12.8) and +1.56 mm Hg for RAP (95% CI 0.85–2.27). The standard deviation of differences was 18.4 for SPAP and 4.5 for RAP. There was a relationship between the differences from their mean value, which is more significant for SPAP. The correlation coefficient for SPAP was 0.43 (p < 0.001) and that for RAP was 0.31 (p < 0.05). Thus, the Bland–Altman analysis revealed a systematic disparity, suggesting a weak agreement of the results of the two methods determining SPAP and RAP. 

Conclusion. Our investigation demonstrated that echoCG proved to be a valid and reliable screening method for PH in patients with SCTD. More accurate estimation of SPAP and RAP measurement requires the application of invasive diagnostic methods.

The role of chemokines in the immunopathogenesis of rheumatoid arthritis (RA) has been actively investigated in recent years. Angiogenic and angiostatic chemokines are important mediators of angiogenesis in the development and extent of pannus. Peripheral blood and synovial fluid (SF) is a major biomaterial in clinical and immunological studies. At the same time, it is the SF test that may yield the most informative results since that gives an idea of the processes that occur locally within a joint.
Objective: to perform a comparative analysis of the levels of a number of CXC, CC, and CX3C chemokines in the SF of patients with RA, osteoarthritis (OA), and joint injuries.
Subjects and methods. The multiplex analysis using xMAP technology (Luminex, USA) was used to analyze levels of CXC, CC, and CX3C chemokines in SF and serum of patients with RA (n = 20), OA (n = 9) and controls (n = 9).
Results and discussion. The SF levels of CCL24/eotaxin-2, as well as those of the angiostatic chemokines CXCL9/MIG, CXCL10/IP10, CXCL11/ITAC, and CXCL13/BCA-1 were higher in the RA group than in the control and OA groups. There was a direct correlation between SF levels of CCL5/RANTES and DAS28, as well as patient global disease activity assessment on visual analogue scale, and that between the level of CCL2/MCP-1 in the SF and that of anticyclic citrullinated peptide (anti-CCP) antibodies in the serum. The SF concentrations of CXCL5/ENA78 and CXCL7/NAP-2 were shown to depend on the presence of serum anti-CCP. Serum CXCL13/BCA-1 levels were higher in RA than those in OA, as that of CXCL7/NAP-2 than in the control group.

Objective: to study the specific features of the symptomatic effect and tolerability of acetaminophen, glucosamine sulfate (GS), chondroitin sulfate (CS), and meloxicam in patents with knee osteoarthritis (OA).
Subjects and methods. An 18-month open-label randomized prospective parallel-group trial enrolled 80 patients with knee OA who fulfilled the American College of Rheumatology criteria and signed the informed consent. They had Kellgren and Lawrence grades O-III OA with visual analogue scale pain intensity of ≥ 40 mm in the target knee, a body mass index of ≤ 35 kg/m2, and no clinical dysfunctions of vital organs and systems. The patients were randomized into 4 groups: 1) acetaminophen 2 g daily; 2) a standard GS regimen; 3) a standard CS regimen; 4) meloxicam 15 mg daily. The patients were followed up for 18 months. The effectiveness was evaluated by the WOMAC questionnaire, Leguesne index, and OMERACT-OARSI (D scenario) during 8 visits. Laboratory and clinical examination as well as electrocardiography were performed. Adverse events were recorded during each visit.
Results. After 4 weeks of treatment, symptomatic improvement was noted in all groups; however, the best effect was achieved by the use of meloxicam that ensured an obvious improvement in all patients. According to the OMERACT-OARSI criteria and changes in the WOMAC and Leguesne indices, the total efficacy of meloxicam was also highest. 20, 10, and 15% of the patients failed to respond to treatment in the acetaminophen, GS, and CS groups, respectively. 
Conclusion. The results of this trial suggest that it is expedient to use GS, CS, and meloxicam long, support the recent guidelines of the European Society for Clinical and Economic Aspects of Osteoporosis and OA (ESCEO), and can give proofs of the efficiency and safety of GS, CS, and meloxicam used in the treatment of knee OA.

The lecture considers the problem of one of the rare manifestations of systemic diseases (pulmonary arterial hypertension) and shows the need for early diagnosis, careful differential diagnosis, and verification of diagnosis, by applying invasive procedures to evaluate central hemodynamics. It gives a model for screening patients with systemic sclerosis, which simplifies the determination of indications for the use of diagnostic verification methods. Current approaches to drug therapy are described and the issues of better survival of patients with poor prognosis of this disorder are discussed. 

The paper considers the mechanisms of action of biological agents and their effect on peripheral blood B-lymphocyte subpopulations in patients with systemic lupus erythematosus and rheumatoid arthritis.

Systemic juvenile arthritis (sJA) is one of the severest childhood somatic diseases. The relevance of the problem associated with sJA is determined by difficulties in early diagnosis, by the rapid development of disability, and by poor prognosis with a high risk for life-threatening conditions. It still persists despite the fact that a notable advance has been made in pharmacotherapy, which could substantially change the prognosis of sJA. The use of disease-modifying anti-rheumatic drugs (DMARDs) and then the advent of biological agents (BAs) have fundamentally changed the drug regimen for the treatment of sJA. The paper considers the aspects of using different DMARDs and BAs in sJA in the context of evidence-based medicine, by analyzing the data available in the literature. 

The paper describes basic steps in the establishment (1964) and development of orthopedic rheumatology and discusses its present-day status. The 50th anniversary of this discipline that is a component of modern rheumatology was celebrated in 2014. In connection with such a remarkable date the author sums up some results of the scientific and practical activities of the orthopedic rheumatologists of the V.A. Nasonova Research Institute of Rheumatology and considers the prospects for further research developments, the possible evolution of minimally invasive surgery (arthroscopic technology for the treatment of large and small joints), and the issues of rehabilitation in a wide range of rheumatic diseases, by applying high technology. 

The paper presents a brief review of the proceedings of the 15th Mediterranean Rheumatology Congress that was held in Istanbul, Turkey, in August 2014. This congress unites the scientists and physicians of Mediterranean countries and focuses the attention of rheumatologists and allied health professionals on the geographical and ethnical features of the pattern of human diseases caused by the inflammatory and metabolic involvement of the locomotor apparatus, as well as the peculiarity of the course of rheumatic diseases and treatment response. The goal of the congress is not only to present information on the latest advances in rheumatology, but also to create conditions for the academic exchange of knowledge at an international level and for the promotion of new investigations.