Reactive arthritis (ReA) is one of the types of spondyloarthritis. According to the statistics reports by the Ministry of Health of Russia, the prevalence of ReA in 2013 was 42.8 per 100,000 adult population, 99, and 172.4 per 100,000 children aged 0–14 and 15–17 years, respectively. There is a wide scatter of ReA detection rates in both the federal districts and subjects of the Russian Federation, which may be associated with both the spread of sexually transmitted infections, asymptomatic trigger Chlamydia infection, and overdiagnosis of ReA.

The paper considers the new gout classification criteria approved by the Board of Directors of the American College of Rheumatology (ACR) and the Executive Committee of the European League Against Rheumatism (EULAR). The criteria have been elaborated on the basis of quantitative assessment of the data obtained during the examinations of patients and have high sensitivity (92%) and specificity (89%). These classification criteria will be able to standardize an approach to making up relatively homogeneous groups of patients having the clinical signs of gout to be enrolled into the investigation.

Objective: to investigate the immunogenicity and safety of 23-valent polysaccharide pneumococcal vaccine in patients with rheumatic diseases (RD).

Subjects and methods. The prospective open-label comparative study enrolled 133 people (102 (76.7%) women and 31 (23.3%) men) aged 23 to 76 years, including 79 patients with rheumatoid arthritis (RA), 16 with systemic sclerosis, and 7 with dermatomyositis/polymyositis, as well as 31 subjects without systemic inflammatory RD (a control group), who had a recent history of at least two cases of lower respiratory tract infections (bronchitis, pneumonia). At their inclusion, all the patients with RD were receiving ant-inflammatory therapy, including 52 taking methotrexate (MT), 14 – leflunomide (LEF), and 13 – MT + tumor necrosis factor-α (TNF-α) inhibitors. The 23-valent polysaccharide pneumococcal vaccine Pneumo-23 (Sanofi Pasteur, France) was administered in a single dose of 0.5 ml subcutaneously during continuous MT or LEF therapy for the underlying disease or 3–4 weeks before the use of TNF-α inhibitors. Clinical examinations of the patients and conventional laboratory studies were performed during control visits (1, 3, and 12 months after vaccination). The serum levels of anti-pneumococcal capsular polysaccharide antibodies were measured in 102 patients by enzyme immunoassay using commercial VaccZymeTM Anti-PCP IgG Enzyme Immunoassay kits (The Binding Site Group Ltd, United Kingdom).

Results and discussion. No clinical and radiological symptoms of pneumonia were recorded in any case during the follow-up period of 12 months. The patients with RD and the control group showed a significant, more than double increase in anti-pneumococcal antibodies 12 months following vaccination. Vaccination was well tolerated: 90 (68%) patients displayed no adverse events; 37 (28%) had pain, cutaneous swelling and hyperemia up to 2 cm in diameter at the site of injection for vaccination;6 (4%) had low-grade fever. There were no episodes of a RD exacerbation or any new autoimmune disorders during the follow-up period.

Conclusion. The findings were suggestive of the sufficient immunogenicity and good tolerability of 23-valent pneumococcal vaccine in patients with RD.

The key component in the management of patients with rheumatoid arthritis (RA) is regular control of RA activity. The quantitative assessment of a patient’s status allows the development of standardized indications for anti-rheumatic therapy.

Objective: to identify the laboratory biomarkers able to reflect RA activity.

Subjects and methods. Fifty-eight patients with RA and 30 age- and sex-matched healthy donors were examined. The patients were divided into high/moderate and mild disease activity groups according to DAS28. The serum concentrations of 30 biomarkers were measured using immunonephelometric assay, enzyme immunoassay, and xMAP technology.

Results and discussion. Multivariate analysis could identify the factors mostly related to high/moderate RA activity according to DAS28, such as fibroblast growth factor-2, monocyte chemoattractant protein-1, interleukins (IL) 1α, 6, and 15, and tumor necrosis factor-α and could create a prognostic model for RA activity assessment. ROC analysis has shown that this model has excellent diagnostic efficiency in differentiating high/moderate versus low RA activity.

Conclusion. To create a subjective assessment-independent immunological multiparameter index of greater diagnostic accuracy than the laboratory parameters routinely used in clinical practice may be a qualitatively new step in assessing and monitoring RA activity.

Rheumatoid arthritis (RA) is a systemic autoimmune rheumatic disease characterized by chronic inflammation of the synovial membrane and a wide range of extra-articular (systemic) manifestations. The main goal of RA therapy is to achieve low disease activity or clinical remission. Power Doppler (PD) ultrasonography (USG) can significantly distinguish between active synovitis (hypervascularization of the synovial membrane) and inactive synovial proliferation.

Objective: to investigate the association between the ultrasonic signs of active inflammation and the clinical and laboratory parameters of disease activity in patients with RA.

Subjects and methods. The investigation included RA patients followed up at the V.A. Nasonova Research Institute of Rheumatology within the first Russian strategic study of pharmacotherapy for RA – REMARCA (Russian invEstigation of MethotrexAte and biologicals for eaRly aCtive Arthritis). A total of 105 RA patients (mean age 51 years), among whom 80% were rheumatoid factor (RF)-positive and 75% were anti-cyclic citrullinated peptide (ACCP)-positive, were examined. In all the patients, methotrexate (metoject, MEDAC, Germany) as the first diseasemodifying anti-rheumatic drug was subcutaneously injected in an initial dose of 10 mg/week with its rapid escalation up to 20–25 mg/week. Then the therapy was added by biologicals as the need arose. The clinical and laboratory parameters were analyzed immediately before and then 12, 24, 36, and 48 weeks following treatment. Therapeutic efficacy was evaluated using the European League Against Rheumatism (EULAR) criteria and activity indices (DAS28, CDAI, and SDAI). USG of eight articular areas (the wrist, second and third metacarpophalangeal, second and third proximal interphalangeal, second and fifth metatarsophalangeal articulations) in the hand and foot of the clinically dominant side was carried out in all the patients prior to treatment and at 12, 24, 36, and 48 weeks after its initiation. Semiquantitative gray-scale (GS) assessment and PD USG were performed according to the OMERACT criteria.

Results and discussion. Weak correlations were found between USG parameters and DAS28, SDAI, and CDAI. After 48-week therapy, the signs of active synovitis were absent in 54 patients and persisted in 51, as evidenced by PD USG. The differences in clinical, laboratory, and ultrasonic parameters were analyzed in relation to USG evidence for active inflammation following 48 weeks of treatment. There were significant differences in GS and PD scores throughout the follow-up period; there were also differences in C-reactive protein levels at 12 and 48 weeks of therapy. No differences were found in clinical activity indices.

Conclusion. The investigation provides support for the important role of USG in assessing the activity of synovitis in RA.

The inflammatory process in the synovial membrane (SM), which may be a main cause of chronic pain in many patients, is one of the most significant components in the pathogenesis of osteoarthritis (OA).

Objective: to study the time course of clinical and sonographic changes in patients with knee OA who used different symptomatic slow-acting agents, such as chondroitin sulfate (CS), glucosamine sulfate (GS), and diacerein, during an 18-month follow-up period in general clinical practice.

Subjects and methods. The investigation enrolled 86 knee OA patients who took CS and/or GS in combination with nonsteroidal anti-inflammatory drugs (NSAIDs) and/or paracetamol in an outpatient setting for 12 months. Clinical and ultrasound (US) studies of the affected knee joints (KJ) were performed at the study inclusion and 12 and 18 months after follow-up initiation. The signs of active synovitis were considered to be increased synovial thickness of up to at least 3 mm and articular fluid accumulation, as evidenced by KJ US study. After 12 months, 36 patients in whom the clinical and sonographic signs of active synovitis persisted were divided into two groups: 1) 19 patients took diacerein instead of CS/GS for the following 6 months; 2) 17 patients in whom the treatment regimen remained unchanged.

Results and discussion. 60.4% of the patients with knee OA were observed to have the sonographic signs of active synovitis, which were weakly correlated with the sizes of osteophytes and the thickness of the hyaline cartilage (r < 0.37). The rate of synovitis decreased to 41.9% during 12-month CS/GS therapy. The patients with persistent sonographically active synovitis had higher visual analogue scale and WOMAC pain scores (p < 0.05), as well as high C-reactive protein levels. They needed the more frequent and longer intake of NSAIDs and paracetamol. During the following 6 months, there was a reduction in the signs of active synovitis, as evidenced by US study, in 78.9 and 6.7% of the patients in Groups 1 and 2, respectively.

Conclusion. Among those with knee OA, there was a subgroup of patients with persistent sonographically and clinically active synovitis, whose treatment demonstrated the efficacy of the interleukin-1 antagonist diacerein.

Pulmonary arterial hypertension (PAH) associated with systemic connective tissue diseases (SCTD) is a poor prognostic manifestation of the latter that result in death if untreated. The invasive determination of hemodynamic parameters is prominent in diagnosing the disease and determining its treatment policy and prognosis.

Objective: to analyze the results of catheterization in PAH-SCTD patients admitted to the V.A. Nasonova Research Institute of Rheumatology.

Subjects and methods. The investigation included 59 patients admitted to the V.A. Nasonova Research Institute of Rheumatology from September 2009 to September 2014. PAH was diagnosed in accordance with the conventional guidelines. All the patients underwent right heart and pulmonary artery (PA) catheterization at the diagnosis and over time during treatment.

Results and discussion. All the patients included in the trial met the pre-capillary pulmonary hypertension (PH) criteria: mean pulmonary artery pressure (MPAP) ≥25 mm Hg; and PA wedge pressure (PAWP) <15 mm Hg. The exclusion of other causes of PH (pulmonary fibrosis, left heart disease, and thromboembolism), as well as a high transpulmonary pressure gradient >15 mm Hg and pulmonary vascular resistance (PVR) >3 Wood units could diagnose PAH in all our patients. There was a statistically highly significant association between pathological hemodynamic changes and functional class (FC). FC was found to be most closely correlated with right atrial pressure (RAP), cardiac output (CO), PVR, and cardiac index (CI). Among the most common manifestations of heart failure, only the presence of peripheral edemas was associated with worse hemodynamic parameters in PAH. It should be noted that out of two biomarkers (N-terminal pro-brain natriuretic peptide and uric acid), the former is largely related to the magnitude of changes in hemodynamic factors. The critical values of hemodynamic parameters were due to extreme edema – anasarca (RAP >17 mm Hg, PVR >20 Wood units, CI <14 ml/m2). Analysis of clinical and instrumental parameters in relation to FC revealed a linear relationship of RAP, CO, and PVR between the level of these parameters and FC; moreover, the highest correlation coefficients were observed for the hemodynamic parameters characterizing right ventricular systolic function. It is remarkable that no MPAP changes were found; only patients with FC IV showed its slight increase (from 51±8 to 55±8 mm Hg; р = 0.087). PAWP remained unchanged regardless of FC.

Conclusion. Thus, the hemodynamic parameters determined in patients with PAH-SCTD during right heart and LA catheterization are closely related to the manifestations of respiratory and heart failure, the biomarkers, and FC of PAH.

Objective: to evaluate the efficacy and tolerability of diacerein in the therapy of primary knee osteoarthritis (OA) with secondary recurrent synovitis.

Subjects and methods. The 3-month open-label randomized controlled trial enrolled 133 patients with OA. Group 1 consisted of 68 subjects (42 women and 26 men; mean age 54.22±4.29 years) who took diacerein 100 mg/day for 3 months. Group 2 (a control group) included 65 subjects (45 women and 20 men; mean age 53.50±3.27 years) who received chondroitin sulfate 1000 mg/day + glucosamine sulfate 1000 mg/day and meloxicam 7.5 mg/day for 3 months too.

Results and discussion. After a therapy cycle, Group 1 patients displayed a statistically significant decrease in the Lequesne index from 13.92±2.16 to 5.95±0.92 (p=0.00005); in Group 2, this index significantly reduced from 16.72±1.78 to 10.76±1.54 (p=0.001). Pain intensity on the visual analogue scale decreased significantly from 70.88±7.06 to 22.05±6.36 mm (p<0.00001) in Group 1 and from 72.46±7.02 to 39.84±6.67 mm (p<0.0004) in Group 2. A persistent analgesic effect was achieved at weeks 6 and 7 in Groups 1 and 2, respectively. The therapeutic effect was estimated as very good and good by 48 and 52% of the patients, respectively, in Group 1 and as good and moderate by 43 and 57% in Group 2. Three months after a therapy cycle effusion in the affected knee substantially increased (from 21.70±6.29 to 29.16±3.63 ml; p<0.001) in Group 2 and slightly increased (from 5.86±3.10 to 6.12±1.09 ml; p>0.05) in Group 1, which confirms the steady-state effect of diacerein. The results of the performed open-label randomized clinical trial showed marked analgesic and anti-inflammatory effect of diacerein and allow to recommend it as the drug of choice to treat knee OA with secondary recurrent synovitis.

Osteoarthritis (OA) is one of the most common rheumatic diseases. Knee OA is particularly frequently encountered among all forms of OA, the prevalence of knee OA being about 25% in the general population. Despite multiple guidelines for the management of knee OA, which have been prepared by the European League Against Rheumatism (EULAR), the American College of Rheumatology (ACR), and the Osteoarthritis Research Society International (OARSI), many problems of its treatment policy remain to be solved. The same holds true for not only the symptomatic and disease-modifying effects of chondroprotectors, but also topical therapy options.

Objective: to evaluate the clinical efficacy and safety of Carmolis gel in patients with knee OA.

Subjects and methods.The trial included 280 patients with knee OA (a study group consisted of 190 patents; a control group comprised 90 patients). The mean age was 58.3±9.3 years in the study group and 59±10.5 years in the control group. The disease duration was 10.3±5.5 and 10.1±4.1 years, respectively. Carmolis gel was applied to the region of the most painful knee joint up to 4–5 times daily, followed by massage of this skin area. The treatment cycle lasted for 2 weeks. No therapy was performed in the control patients. The clinical efficacy was determined by the changes in joint pains at rest or on movement and palpation, according to a visual analogue scale (VAS), WOMAC questionnaire, the synovitis intensity (assessed by ultrasonography), patient and physician global assessments of disease activity (Likert scale), and the possibility of reducing the daily dosage of nonsteroidal anti-inflammatory drugs (NSAIDs). The onset the therapeutic effect of the gel and the duration of its action were recorded.

Results and discussion. The topical application of Carmolis gel caused a statistically significant reduction in joint pain at rest and on movement from 57.7±6.8 to 12±1.8 mm (р < 0.01) and from 52±5.3 to 17±2.7 mm, respectively (р<0.01). The WOMAC showed similar pain changes. In the study group, the WOMAC pain level averaged 210±20.5 mm at baseline and reduced to 101±12.8 mm after the treatment (p < 0.01).The control group also exhibited pain relief, but to a much lesser degree than did the study group. There were no statistically significant differences between the groups in motor and day-to-day activity changes. After treatment, the patients of both groups had reduction in the signs of synovitis; however, no differences were found between the groups. The dose of NSAIDs could be decreased in 99 (52.1%) of the 190 patients in the study group and only in 15 (16.6%) of the 90 patients in the control group (p<0.05). Carmolis gel was well tolerated. No adverse events were observed in 184 patients. Local cutaneous reactions and itch were noted in 6 (3.2%) patients; however, they were short-term and did not required drug discontinuation.

Conclusion. The findings suggest that the incorporation of Carmolis gel into the combination therapy of OA ensures a significant reduction in joint pain and allows the dose of NSAIDS to be decreased, making the treatment safer.

Coxitis is one of the characteristic clinical manifestations of ankylosing spondylitis (AS). Hip joint (HJ) damage in AS is regarded as a poor prognostic factor and the early detection of coxitis is of great importance, as timely adequate therapy may reduce the risk of irreversible HJ changes. Coxitis may be diagnosed clinically and using different imaging techniques, each of which can characterize different aspects of damage of these joints. The lecture considers the clinical and instrumental diagnosis of coxitis in AS.

Interleukin 6 (IL-6) is one of the key cytokines that are involved in inflammation and that has pleiotropic properties. Diverse effects of IL-6 result from the transmission of an intracellular signal in two ways: via direct binding to a membrane receptor having a molecular mass of 80 kDA (a classical way) or absorption of the IL-6 complex with its soluble receptor on another transmembrane receptor – gp-130 (trans-signaling). Different signaling pathways lead to various consequences. The classical way of signal transmission activates mainly protective and regenerative processes; trans-signaling has a proinflammatory potential. The review gives schemes of signal stimuli and shows that IL-6 and its receptors are a dynamic intricately organized regulatory system that can adapt to stress-induced homeostatic changes. It considers in detail evidence suggesting the effect of IL-6 on the development and maintenance of a number of systemic sclerosis (SS)-specific pathogenetic disorders, such as the activation of the endothelium, the development and maintenance of inflammation, and excessive deposition of extracellular matrix components in tissues. Endothelial cell activation during trans-signaling gives rise to an enhanced adhesion molecule expression, chemokine release, and further production of IL-6. Excessive secretion of the latter may initiate a fibrosing process and favor the further development of pathological
conditions. Autoimmune disorders theoretically associated with IL-6 overproduction occur in SS. Elevated blood IL-6 concentrations in SS are related to disease clinical parameters, such as activity, severity, worse prognosis, and reduced survival. Taken together, the data presented suggest that IL-6 blocking may have a therapeutic potential in SS. The first clinical data on successfully using the IL-6 receptor antagonist tocilizumab to treat SS are given.

The paper gives the results of the RAPID-axSpA study that has evaluated for the first time the efficacy of the tumor necrosis factor-α (TNF-α) inhibitor certolizumab pegol (CZP) in treatment of axial spondyloarthritis (axSpA) clinical forms: already developed ankylosing spondylitis and non-radiographic axSpA. CZP was shown to be effective in all forms of axSpA, whether radiographically detected sacroiliitis was present or absent. This study has also demonstrated for the first time the long-term efficacy of TNF-α inhibitors in patients with initially high C-reactive protein level and/or signs of active sacroiliitis by magnetic resonance imaging.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Coronary vascular catastrophes are one of the main causes of death in RA. Despite this, a cardiovascular risk assessment procedure that should take into account the clinical and pathogenetic features of RA has not been developed so far. The review considers whether cardiac autonomic neuropathy (CAN) and heart rhythm variability (HRV) are associated with cardiovascular diseases. Much attention is also given to the significance and prevalence of CAN among patients with RA. There is information on the impact of inflammation and RA therapy on the course of CAN and HRV values. The accumulated evidence provides a way of considering HRV as a promising additional method to evaluate the severity of target organ damage, cardiovascular risks, and therapeutic efficacy in patients with RA. However, further investigations are needed to elaborate 
guidelines for using HRV estimates in RA.

The paper describes a case of microscopic polyangiitis (MPA), the first clinical manifestation of which has been joint damage characterized chiefly by arthralgias. The overproduction of rheumatoid factor and anticyclic citrullinated peptide antibodies served as the basis for assuming rheumatoid arthritis (RA). Two years after disease onset, there were the first signs of glomerulonephritis (GN) that further progressed to severe kidney failure. MPA was diagnosed by a renal biopsy that revealed the morphological pattern of immunonegative GN with glomerular crescents. The diagnosis was verified by the presence of serum antineutrophil cytoplasmic antibodies (ANCA). There were no X-ray bone changes typical for RA at a 10-year follow-up. The paper discusses whether it is important to incorporate ANCA-associated systemic vasculitis into a diagnostic search in patients with early arthritis, particularly when the latter is concurrent with involvement of the kidney or other organs.

By the end of the first decade of the 21st century, spondyloarthritis studies have accumulated a certain number of terms that are obsolete, but used by physicians in their everyday speech, on the one hand, and a great variety of different definitions, on the other hand. In January 2014, the first organizational meeting of the Expert Group on Spondyloarthritis, Association of Rheumatologists of Russia, decided that its primary task should be to order the terminology used in this area. The authors primarily collected the terms, which had been already used in medical vocabulary, and then divided them into two categories: obsolete definitions and terms to be finalized and unified. This publication gives guidelines for using the medical terms relevant to spondyloarthritis and separately discusses how to correctly write the term sacroiliitis.

The 16th Annual European Congress of Rheumatology, which is indubitably the central event of international rheumatology, took place in Rome on 10–13 June 2015. It was attended by around 14,000 delegates (physicians, healthcare workers, patients) from more than 100 countries of the world. A total of 4,300 theses were considered; 82% of them were selected to be published. The program of the congress was extremely diverse; it included discussion of new data on the diagnosis and treatment of the most common rheumatic diseases, their etiology and pathogenesis, personified therapy, and many other problems. This communication presents in more detail materials reflecting current trends in the treatment of rheumatoid arthritis.