Objective: To review the effects of the biologic monoclonal anti-CD-20 antibody, rituximab, on renal and non-renal systemic lupus erythematosus in both uncontrolled and controlled studies. Summary: Uncontrolled studies have demonstrated potential for rituximab in treating lupus patients, but two controlled trials, one each in renal and non-renal lupus, did not confirm this. There remain reasons to believe that these controlled trials may have not been designed optimally and additional controlled trials are currently being planned to provide more data on this issue. In this review, we introduce rituximab and investigate both controlled and uncontrolled observations involving this drug. We also discuss possible reasons for the differences between their findings and provide suggestions for potential avenues of investigation, i.e. treatment dosages, concomitant treatment, and study length. Finally, we introduce three upcoming controlled trials that seek to address these important unsolved questions.

Objective: to study the distribution of the genotypes of the vascular endothelial growth factor (VEGF) gene and their combinations with those of other cytokines among patients with rheumatoid arthritis (RA) and healthy individuals. Subjects and methods. 509 Europeoid women from the eastern regions of Russia, including 374 healthy individuals aged 23-64 years and 135 RA patients aged 27-66 years, were examined. The single nucleotide polymorphism in the promoter region of the genes of VEGC -2578 C/A, tumor necrosis factor-а (TNF-а) -863 C/A, TNF-а -308 G/A, TNF-а -238 G/A, and interleukin (IL) 1β -31 С/T, IL4 -590 С/T, IL6-174 G/C, IL10-1082 G/A, and IL10-592А/С was studied by restriction fragment length polymorphism analysis. Results. Analysis of the frequency of the genotypes of VEGF in combination with other genotypes has revealed a number of highly significant genetic differences between the groups of healthy individuals and RA patients. Among the combined genetic signs (CGS), whose frequency is significantly increased in RA, there is a predominance of heterozygous CA genotypes at the polymorphic position of VEGF -2578 C/A. Among the CGS positively associated with RA, which include homozygous VEGF -2578 variants, there is a preponderance of AA genotypes whereas all 100% of the homozygous genotypes, whose frequency is significantly decreased in RA, correspond to the variant of СС. The CGS whose frequency is altered in RA along with VEGF genotypes most commonly include the genotypes of IL1ß, IL4, IL10, IL6, and TNF-а. Conclusion. The pathogenesis of RA calls for comprehensive investigation of the role of the angiogenesis and inflammation regulation genes.

Objective: to assess how the Russian version of the international «treat-to-target» (T2T) recommendations can be understood by patients with rheumatoid arthritis (RA) and the extent to which they consent to their content. Material and methods. At Stage 1, the principles and recommendations of the international T2T version for patients were translated into Russian and agreed upon by the Russian Federation's Working T2T Expert Group members and one patient. At stage 2, the project was discussed and edited at a one-day conference with the participation of 15 RA patients (11 women and 4 men at the age of 28 to 64 years) from 6 regions of Russia. Consensus on its final version was achieved. At stage 3, eighty-six RA patients (77 women and 9 men at the age of 20 to 72 years with a disease duration of 3 months to 18 years) from 7 Russian regions (including 75.6% from the Central Federal District) assessed the clarity of translation of each principle (A-D) and each recommendation (1-10) into an unprofessional language and the degree of consent to its content, by using the 10-point Likert scale (0 = strongly disagree; 10 = strongly agree). Results. The consent of the patients to the translation and content of the T2T principles and recommendations was more than 8.7 scores. The mean level of translation clarity into the unprofessional language was 9.41 scores (from 8.82 scores for Recommendation No. 6 to 9.88 scores for Recommendation No. 10), that of consent to the content was 9.34% scores (from 8.76 scores for Recommendation No. 4 to 9.79 scores for Recommendation No. 10). The minimum level of consent was observed for Recommendations No. 3 (low disease activity as an alternative to remission) and No. 4 (drug therapy reconsideration frequency) was 8.85 and 8.76 scores, respectively. The consent to the content of Recommendation No. 3 was lower in the very early and early stages of the disease (7.93 scores) and higher in the extended and late stages (9.6 scores). In young patients aged 20 to 40 years, the consent to Recommendation No. 4 was higher (9.54 scores) and in those aged 41 to 72 years, that was lower (8.31 scores). There were no differences in the perception of the recommendations, depending on the level of education. The maximum level of consent to General Principle No. 1 (joint decision with a patient about treatment) and Recommendation No. 10 (patient awareness of the treatment goal and its achievement strategy) was 9.73 and 9.79 scores, respectively. Conclusion. There is a high level of consent to the content of the principles and recommendations of the Russian T2T version for patients. The content to Recommendation No. 3 increases with longer disease duration and that to Recommendation No. 4 decreases with age. In the future, it is necessary to assess a relationship between the degree of consent and the T2T recommendations and geographical indications and to reveal associations and differences in the perception of the recommendations among physicians and patients. This approach is able to remove obstacles to introduce the T2T initiative in real clinical practice and to optimize the results of RA treatment.

Objective: to estimate the contribution of arthrosonography to the diagnosis of metatarsophalangeal joint (MTPJ) injury and to reveal predictors for functional impairments in patients with rheumatoid arthritis (RA). Subjects and methods. The investigation enrolled 50 patients with the RA diagnosis meeting to the American College of Rheumatology 1987 criteria. According to disease duration, the patients were divided into two groups: 1) 9 patients with an early RA history of less than 2 years (ERA); 2) 41 patients with a RA history of over 2 years (LRA). All the patients underwent clinical joint evaluation, laboratory and instrumental examination, including joint X-ray and ultrasonography (USG). Results. An inflammatory process in the foot joints is significantly more frequently detected on ultrasound than clinically (p < 0.0001). The detection rate of erosions, as evidenced by USG, was significantly higher than that by X-ray, in ERA in particular (p = 0.01). Comparison analysis of patients with low and high HAQ scores showed the relationship between functional status, age, pain degree, and inflammatory process in the fifth MTPJ, as shown by USG. There were no associations with disease duration, traditional clinical and laboratory parameters of RA activity, and erosive changes in the feet. Conclusion. Joint USG in daily clinical practice makes it possible to objectively evaluate pathological changes in the feet and the probability of work disability due to RA.

Objective: to specify the association between the levels of proinflammatory cytokines, such as tumor necrosis factor-а (TNF-а), interleukin-1 β (IL-1 β), and IL-6, and the presence and degree of depression and anxiety spectrum disorders (ADSDs) in patients with rheumatoid arthritis (RA). Subjects and methods. The investigation included 45 patients with a valid RA diagnosis. Their mean age was 45.5+3.09 years; the mean disease duration was 155.0+26.5 months. The authors determined RA activity with the DAS28 index; fatigue degree with the Fatigue Severity Scale (FSS), and pain magnitude with the Brief Pain Inventory (BPI). Mental disorders were diagnosed by a psychiatrist in accordance with the ICD-10 and DSM-IV, by applying a number of psychiatric and psychological scales and tests. The concentration of proinflammatory cytokines was measured using the xMAP (27-plex) technology on a BioPlex-200 analyzer (Bio-Rad, USA). Results. There were mental ADSDs in 82.2% of the patients and moderate cognitive impairments (CI) in 67.7%. 80% of the examinees reported clinical fatigue; 64.5% experienced severe and moderate pain. The levels of TNF-а and IL-1ß were slightly higher in patients with ADSDs and CI than in those without these disorders. The concentration of IL-6 was highest in the presence of anxiety disorders. However, these differences were statistically insignificant. The level of TNF-а was somewhat higher in patients with clinical fatigue and significantly higher in those who experienced intense pain. That of IL-1ß was significantly higher in patients with severe and moderate pain than in those with mild pain (p < 0.05). Conclusion. ADSDs and CI in patients with RA are associated with the elevated levels of proinflammatory cytokines (TNF-а, IL-1ß, and IL-6), which confirms the implication of chronic inflammation in the pathogenesis of these conditions in RA. High TNF-а and IL-1ß levels are typical of RA patients with clinical fatigue and marked pain.

Objective: to assess an association between the levels of anti-cyclic citrullinated peptide antibodies (anti-CCP), anti-modified citrullinated vimentin antibodies (anti-MCV), rheumatoid factor (RF), and X-ray signs of destructive changes in RAjoints. Subjects and methods. One hundred and fourteen patients with RA were examined. All the patients received therapy with disease-modifying antirheumatic drugs and 61.4% took glucocorticoids. The investigators determined erythrocyte sedimentation rate (ESR) by the Westergren method, serum anti-MCV concentrations (U/ml) by enzyme immunoassay (EIA), anti-CCP levels by electrochemiluminescence and EIA. The modified Sharp method was used to quantify X-ray changes. Results. The total Sharp score (TSS; Me [the 25th and 75th percentile]) was 89 [57; 117]; the number of erosions and stenoses was 9 [3; 27] and 76 [51; 99], respectively; anti-MCV levels were 470.2 [106.9; 1000] U/ml. According to the level of RF IgM-, anti-CCP-, and anti-MCV-positivity, all the patients were divided into groups. High anti-MCV positive patients (n = 80) were observed to have higher TSS (96.5 [66.0; 120.0]), a larger number of stenosis (82.0 [60.5; 105.5]), and greater inflammatory disease activity (ESR, 40 [30; 61]) than negative/low positive patients (n = 25) who had 57 [31; 88], 50 [29; 82], 30 [21; 48.5] respectively; p < 0.05). No significant differences in joint destruction were found in the patient groups according to RF IgMand anti-CCP-positivity. Conclusion. Anti-MCV shows a greater degree of bone destruction and is associated with higher inflammatory disease activity than anti-CCP.

Objective: to define the rate and nature of lower back pain (LBP) in outpatients seeking medical care at Republican Hospital One — National Center of Medicine in Yakutsk. Subjects and methods. A total of 1072 patients (343 (32%) males (mean age 44.9+14.9 years) and 729 (68%) females (mean age 49.8+12.2 years)) seeking medical assistance were asked using questionnaires. Results. Out of the 1072 respondents, 415 patients complained about LBP. Twenty-seven patients were found to have probable specific diseases and 47 had nerve root pains. LBP was chronic in 341 of the 415 patients. Conclusion. LBP is a common reason for patients seeking outpatient care. In the majority of cases, they sought medical assistance for chronic nonspecific pain.

Objective: to study the specific features of regulation of peripheral vascular tone and their association with the endothelial structure and function of large vessels in patients with scleroderma systematica (SDS). Subjects and methods. The investigation enrolled 25 patients with SDS (mean age, 47±2.6 years; mean disease duration, 8.3+1.7 years) and 15 apparently healthy individuals matched for age and gender. Comprehensive examination involved laboratory and instrumental studies, laser Doppler study to evaluate endothelium-dependent and endothelium-independent vasodilation, as well as applanation tonometry calculating the pulse wave velocity and augmentation index. Results. All the patients were found to have impaired peripheral vascular responsiveness as compared to the controls. The examination established a relationship between the magnitude of endothelium-dependent vasodilation and the stiffness index of large vessels. There was no association between endothelium-independent vasodilation and vascular elasticity parameters.

Objective: to estimate the informative value and reproducibility of ultrasound study (USS) in interstitial lung disease (ILD) in patients with scleroderma systematica (SDS) and to compare ultrasound lung comet (ULC) scores with the data of multislice spiral computed tomography (MSCT) of the lung and its function tests. Subjects and methods. Forty patients with SSD and ILD were examined. According to the extent of lung injury, the patients were divided into two groups: 1) 12 patients with significantly pronounced changes (>20% lung involvement, as evidenced by MSCT); 2) 28 patients with just noticeable changes (<20% lung involvement). ULC scoring was used to record the results of lung USS. Results. In the SDS patients from Group 1, the ULC scores were significantly higher than those in Group 2 (113.6+48.3 and 35.3+32.7, respectively; р < 0.0005). Those in the entire group were inversely correlated with forced vital capacity (r = -0.56; р < 0.05) and diffuse lung capacity (r = -0.57; р < 0.05). Assessment of the reproducibility of ULC scoring disclosed no significant differences in the data obtained by two investigators; the Kendall concordance coefficient turned out to be rather high (r = 0.81; p < 0.001). Conclusion. Lung USS may be used as a simple, well-reproducible additional study of ILD in SDS, which can identify lung fibrosis and estimate its extent.

The paper analyzes the incidence of acute rheumatic fever (ARF) and chronic rheumatic heart disease (CRHD) and theirs outcomes in the Tula Region in 1991 to 2011. In this period, the incidence of ARF decreased to 0.002, which was much lower than Russia's rates. That of CRHD in 2011 accounted for 1.6 per 1,000 adult population, which was comparable to the values in Russia. CRHD mortality rates showed a 2.5-fold decrease. The main causes of fatal outcomes were cardiovascular disorders.

The recent rise in survival rates and therefore in the degree of organ damages due to both disease itself and performed therapy increasingly gives a reason to think about health-related quality of life (QL) in patients with systemic lupus erythematosus (SLE). Numerous studies initiated in the 1980s to asses QL in patients with SLE have revealed considerable impairments in physical, emotional functioning in this category of patients. SLE leads to social dysadaptation, chronic stress, anxiety, and depression. Timely detection of worse QL in patients and correction of depressive disorders improve patient compliance. Six SLE questionnaires were validated to study health-related QL; these were Medical Outcomes Study 36-Item Short Form Health Survey (MOS SF-36) SLE Symptom checklist, SLE QL Questionnaire (SLEQol), Lupus QL Questionnaire (LupusQol), LQol, and Lupus Patient Reported Outcome Tool (LupusPRO). The general MOS SF-36 and specific Lupus Qol that has been developed for SLE patients are available in Russian. To study QL in the patients at the present stage of rheumatology development is an important component of SLE cura-tion both in real clinical practice and during international clinical trials as one of the components of therapy assessment.

Proton pump inhibitors (PPIs) are the most important class of drugs used for the therapy of acid-dependent diseases and states of the gastrointestinal tract (GIT). In rheumatologic practice, PPIs are an essential drug to treat and prevent upper GIT pathology occurring with the intake of antirheumatic (above all nonsteroidal anti-inflammatory) drugs. PPIs are noteworthy for ease of use, efficacy, and excellent tolerability. Nevertheless, they are able to cause a number of serious class-specific adverse reactions. Some of these complications, such as osteoporosis progression and metabolic effect of methotrexate, may be of great importance for rheumatologic practice. This review is a critical analysis of the data available in the literature on the safety of PPIs and a risk-benefit assessment when they are used