The use of the current standards for laboratory diagnosis of rheumatic diseases (RD) in clinical practice was analyzed on the basis of the data obtained at the Laboratory for the Immunology and Molecular Biology of Rheumatic Diseases, V.A. Nasonova Research Institute of Rheumatology, Russian Academy of Medical Sciences, in 2012. A total of 19,900 patients with RD were examined; 90,364 tests (mean 4.5 tests per patient), 57,338 (63.6%) autoantibody tests, 11,661 (12.9%) acute-phase inflammatory protein tests, and 21,365 (25.5%) tests for other biomarkers were carried out. There were also 27,026 (30%) tests for antinuclear antibodies; 7,027 (7.8%) for rheumatoid arthritis, 8,194 (9.1%) for cyclic citrullinated peptide antibodies, 8,353 (9.2%) for antiphospholipid antibodies, and 2,550 (2.8%) tests for antineutrophil cytoplasmic antibodies. C-reactive protein was measured in 10,845 (12.0%) tests; IgG, IgG4, IgM, and IgA in 7,178 (7.9%); complement in 4,978 (5.5%); cryoglobulins in 2,578 (2.9%); lymphocyte subpopulations in 950 (1.1%); and antistreptolysin O in 1,156 (1.3%). Autoantibodies and acute-phase indicators were shown to be of the greatest clinical value among the laboratory biomarkers of RD. In real clinical practice, the diagnostic sensitivity and specificity of and positive and negative likelihood ratios for laboratory tests can differ from those when examining specially selected groups of patients and healthy individuals. In this connection, the use of laboratory tests and the assessment of their results require strict compliance with presumptive diagnosis and the data of a thorough clinical examination of patients.

Objective: to study the association of polymorphic variants of the genes playing a pivotal role in the processes of inflammation with the efficiency of tocilizumab (TCZ) therapy in patients with active rheumatoid arthritis (RA). Subjects and methods. The investigation enrolled 43 patients with active RA resistant to standard therapy with disease-modifying antirheumatic drugs who had previously received no genetically engineered biological agents. The patients received 6 intravenous infusions of TCZ in a dose of 8 mg/kg at 4-week intervals. DAS28 was used to evaluate the efficiency of TCZ therapy. Polymorphisms in the genes of interleukin 6 (IL-6) (-174G/C), IL-6 receptor (IL-6R) (+358A/C), tumor necrosis factor-а (TNF-а) (-308A/G), IL-10(-592A/C, -1082A/G), TNF^-Induced protein 3 - TNF-αIP3 T/C (rs675520), TNF-αIP3A/G (rs6920220), monocyte chemoattractant protein 1 - МСР1 (+2581A/G) were detected by a real-time polymerase chain reaction assay using fluorescently-labeled specific hybridization primers, followed by melting curve estimation by means of a DT-96 detecting amplifier (ZAO «Scientific Production Firm DNA-Technology», Russia). Results. Logistic regression analysis revealed that a therapeutic response to the first TCZ infusion was associated with the polymorphism of the TNF-а (-308A/G) gene; the odds ratio (OR) was 8.0 [95% confidence interval (CI) 1.2-52.8] (p = 0.03). The carriers of the GG genotype demonstrated a less marked response than those of the AG genotype (the AA genotype was not found). After the sixth TCZ infusion, there was an obvious trend towards a statistically significant correlation of the clinical response with the polymorphism of the TNF- аIP3 A/G (rs6920220) gene (OR = 5.5; 95% CI 0.9-32.6; p = 0.06). A good response was more frequently observed in the carriers of the homozygous GG genotype than in those of the AA/AG genotypes (68.6 and 31.4%, respectively) and, conversely, a moderate response was more common in the carriers of the AA/AG genotypes than in those with the GG genotype (71.4 and 28.6%, respectively; p = 0.06). The same polymorphism in the logistic regression analysis was identified as a prognostic marker for clinical remission (OR = 4. 2; 95% CI 1.1-16.7; p = 0.04). Conclusion. The therapeutic response to the first and sixth TCZ infusions was associated with the TNF-а and TNF-αIP3 genes playing a significant role in the activation and regulation of the nuclear factor kB (NF-kB) signaling pathway.

Objective: to estimate the value of simplified ultrasound (US) indices of synovitis in the most commonly involved joints of the dominant hand, which are studied using the grey scale mode while monitoring the efficiency of tocilizumab (TCZ) therapy in patients with rheumatoid arthritis (RA). Subjects and methods. Forty-six patients with RA confirmed by the 1987 American College of Rheumatology (ACR) criteria who had been ineffectively treated received TCZ infusions for 6 months. The patients were stratified into two groups: 1) 11 patients with early (<2-year) RA (ERA); 2) 35 patients with protracted (>2-year) RA (PRA). Disease activity and therapy efficiency were determined by DAS28-CRP, SDAI, and US study of the dominant hand joints most commonly involved in the pathological process. Results. The evaluation of TCZ therapy from the simplified US indices reflected synovitis regression in the dominant hand joints of patients with ERA. The highly significant correlations between the changes in US parameters and RA activity the indices ^US-wrist/iDAS28-CRP: r = 0.75; p = 0.01; ΔUS-S8/ΔDAS28-CRP and ΔUS-S5/ΔSDAI: r = 0.65; p < 0.05) confirm the validity of the above changes. No reduction in the joint indices was observed in the patients with PRA. Conclusion. The simplified grey-scale US indices of synovitis in the joints of the dominant hand (including one wrist joint) is an accessible noninvasive method for evaluating the efficiency of the therapy performed in patients with ERA.

Objective: to study the impact of pain intensity on the progression of knee osteoarthrosis (OA). Subjects and methods. One hundred and ten patients with knee OA were examined at a 5-year interval. All the patients underwent a questionnaire survey and knee joint pain assessment using a visual analog scale (VAS) and standard radiography. Results. After 5-year follow-up, radiographic OA progression was seen in 40 patients (Group 2); its stage remained the same in 70 patients (Group 1). In both groups, the patients were matched for age (59.2+9.5 and 59.0+8.1 years) and disease duration (11.1+10.6 and 13.7+9.9 years). During the first examination, pain on walking was more severe in Group 1 than in Group 2: 57.8+16.6 and 48.7+13.3 mm by VAS (р=0.002), as well as severe joint pain was predominant in these patients: 22.5 and 11.4%, respectively. Over the 5-year period, there was an increase in pain intensity. At the end of the follow-up, the patients with progressive OA rated their knee joint pain as severe in 35% of cases whereas in this index the non-progression group was only 12.9 (p = 0.012). Conclusion. In the OA progression group, pain intensity was initially statistically higher than that in the non-progression group. During 5-year follow-up, Group 1 showed an increase in knee joint pain intensity on walking, which can be considered as one of the predictors of gonarthrosis progression.

The clinical value of the disorders and diseases integrated within the metabolic syndrome (MS) is in the combination of traditional risk factors for cardiovascular diseases (CVD), which significantly accelerates the development of cardiovascular events (CVEs). The detection rate for MS in patients with rheumatoid arthritis (RA) is shown to be higher than in the controls regardless of the diagnostic criteria for MS. At present, there are confusing data on the role of adipokins in RA. Objective: to determine the rate of MS and its components in RA patients and the association of the level of adipokin (adiponectin) with the components of MS in relation to the duration of RA. Subjects and methods: The investigation enrolled 69 RA patients divided into two groups: 1) 34 patients with early-stage (<2-year) RA and 2) 35 patients with end-stage (>2-year) RA. Results. MS occurred in 12 (17.4%) of the 69 patients with RA. There was central (abdominal) obesity in 37 (53.6%) patients with RA, hypertension in 29 (42%), low high-density cholesterol levels in 20 (29%), hyperglycemia in 11 (15.9%), and hypertriglyceridemia in 10 (14.5%). According to the presence or absence of MS, the patients were divided into 2 groups: 1) 12 patients with MS; 2) 57 without MS. In the patients with RA and MS, the duration of the disease was shorter; DAS28 and CDAI were higher than in those without MS: 15.4 [7; 24] months versus 51.8 [6; 72] months; DAS28 was 5.8 [4.9; 6.7] scores versus 5.1 [4.5; 5.8] scores; CDAI: 34.8 [21.8; 41.4] scores versus 24.2 [18; 31] scores, respectively (p < 0.05 in all cases). The serum level of adiponectin was lower: 13.1 [5.7; 10.7] ng/ml versus 20.6 [6.9; 30.9] ng/ml in the patients with RA and MS as compared to those without MS; but there were no significant differences. In the patients with early-end RA, the rate of MS was twice higher than that in those with end-stage RA; however, the differences were statistically insignificant (p = 0.1). The components of MS were encountered with the same frequency in early- and end-stage RA. The early RA group showed a correlation between SDAI (r = -0.34), body mass index (r = -0.41), high-density lipoprotein cholesterol (r = 0.33), erythrocyte sedimentation rate (r =-0.35), and adiponectin. The >2-year RA group displayed no relationship between adipokins, activity markers, and metabolic disturbances. Conclusion. The preliminary results suggest the high rate of MS in patients with a high level of early RA disease activity untreated with disease-modifying antirheumatic drugs, thus determining the high risk of CVEs just at disease onset. The role of adiponectin in the development of MS, CVEs in rheumatic diseases remains to be solved, which is the subject of further investigations. It is possible that normalization of adiponectin concentrations may promote reductions in the incidence of CVD, mortality rates due to atherosclerosis-induced CVEs, and the prevalence of MS and insulin resistance.

Fibromyalgia is a disease accompanied by diffuse chronic pain for >3 months and tenderness on palpation in at least 11 of 18 anatomic points (American College of Rheumatology criteria). Gnathalgia was also included in the revised fibromyalgia criteria in 2010. Some patients have facial pain spots, symptoms and signs of temporomandibular dysfunction in combination with chronic fatigue and sleep disorder. The paper presents the results of an anonymous questionnaire survey in patients with a valid diagnosis of fibromyalgia. The patients with this disease require a follow-up by a family physician, a rheumatologist, and a dentist.

Objective: to evaluate the efficiency of a comprehensive rehabilitation program (CRP) in patients with early rheumatoid arthritis (RA) for 6 months. Subjects and methods. Sixty patients with early RA were examined. During medical therapy, 6-month CRP was implemented in 34 patients in the study group. The 2-week in-hospital stage involved ten sessions of 15-min local air cryotherapy (-60 °C) of the hands, knee or ankle joints; ten classes of 45-min therapeutic exercises (TE) under the supervision of a trainer; ten sessions of 45-min ergotherapy (training people how to therapeutically position their joints, to apply their protective methods, to lift and move things, to use assistive devices, and to do hand exercises); orthotics (working wrist orthoses, knee ones, or individual orthopedic insoles); and four 90-min educational program classes. The outpatient and domiciliary stages included 45-min TE thrice weekly; creation of a correct functional stereotype; and orthotics. Twenty-six patients received medical therapy only (a control group). The authors estimated tender joint count (TJC), swollen joint count (SJC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), joint pain on 100-mm visual analog scale (VAS), DAS28, HAQ, RAPID3, hand grip strength, average maximum knee extension and ankle flexion by the EN-TreeM movement analysis, and compliance with drug and non-drug treatments. Results. The study group showed a stably high compliance with therapy with disease-modifying antirheumatic drugs, less need for symptomatic agents, higher adherence to the methods of creating a correct functional stereotype, orthotics, and regular TE. Twenty-two patients completed 6-month CRP; 12 patents did not complete the treatment because of non-compliance with nondrug methods, primarily TE. Upon completion of the in-hospital stage of CRP, the study group exhibited significant positive changes in pain and functional status and no significant impact on global inflammatory activity indicators (SJC, ESR, CRP, and DAS28). After 6 months of CRP, there were reductions in TJC by 6.0+1.8 or 72.3% (p <0.01), SJC 4.0+1.2 or 74.1% (p <0.01), ESR by 58.2% (p < 0.01), CRP by 67.2% (p < 0.01), VAS pain by 70.4% (p < 0.01), DAS28 by 1.38+0.21 scores or 31.9% (p < 0.05), HAQ by 0.97+0.56 scores or 75.8% (p < 0.01), and RAPID3 by 5.98+0.92 scores or 60.1% (p < 0.01). The grip strength of a more and less affected hand increased by 44.9% (p < 0.05) and 31.3% (p < 0.05), respectively. The average maximum extension of a weaker and stronger knee joint increased by 88.7% (p < 0.01), and 67.7% (p < 0.01), respectively. The average maximum flexion of a more and less affected ankle joint rose by 81.6% (p < 0.01) and 70.2% (p < 0.01), respectively. Following 6 months, the changes in the control group were less significant, which determined significant differences between the groups in most indicators. Conclusion. Six-month CRP enhances compliance with drug and non-drug treatments, assists in controlling disease activity, and improves functional abilities, motor activity, and quality of life in patients with early RA. The main reason for CRP interruption is inadequate patient adherence to non-drug treatments.

In pediatrics, rheumatic diseases (RD) are characterized by particularly severe social consequences. This investigation was undertaken to clarify the prevalence of RD from the 2009—2010 statistical data of the Ministry of Health and Social Development of the Russian Federation. Analysis of these data has led to the conclusion that the acute rheumatic fever situation is relatively favorable in Russia. As for musculoskeletal system diseases, patients with inflammatory RD are a small percentage among those with this pathology; however, they are critically ill and become disabled early and frequently despite the fact that the majority of novel highly effective drugs have not approved for use in children, which makes their timely use difficult. Most children with locomotor diseases suffer from non-inflammatory diseases. This shows the importance of measures for the prevention, early detection, and correction of acquired or inherited pathology of the joints and vertebral column.