There are virtually no diagnostic tests that can diagnose diseases of the musculoskeletal system and connective tissue with 100% sensitivity and 100% specificity, which was the reason for making both diagnostic and classification criteria to help practitioners and investigators. The application of these criteria is discussed in the article.

In early 2016, the international group of expert members of the European League Against Rheumatism (EULAR), the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA), and the European Vasculitis Society (EUVAS) published new guidelines for the diagnosis and management of antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis (SV). These guidelines are an important step in the development of the concept of ANCA-SV and have resulted from the systematic generalization of current scientific achievements and clinical experience. Fifteen recommendations proposed by the EULAR/ERA-EDTA highlight a wide range of problems of ANCA-SV and should contribute to the improvement of the diagnosis, efficiency of therapy and prognosis of these diseases. The aim of the publication is to provide the general characteristics of the main provisions of the guidelines.

The article summarizes the data of two randomized controlled trials (RCTs) Phase III MEASURE 1 and MEASURE 2 investigating the efficacy and safety of secukinumab (SEC) in treating ankylosing spondylitis (AS) and compares the data with the results obtained from Russian patients with active AS, who were enrolled in these RCTs.

Subjects and methods. Among 590 patients included in the MEASURE 1 and MEASURE 2 trials, the Russian group totaled 107 patients: 44 and 29 patients took SEC in the MEASURE 1 and MEASURE 2 trials, respectively; 34 patients had placebo in the two trials.

Results and discussion. A retrospective analysis of the results for the Russian patient group showed that the efficacy of SEC in treating AS was fully similar to that demonstrated in the entire MEASURE 1 and MEASURE 2 group cohort. At 1 to 16 weeks of SEC therapy, the MEASURE 1 trial Russian patients displayed a rapid clinical improvement in 52.6% (p = 0.043); and in the SEC 150- and 75-mg groups, ASAS20 improvement was achieved by 64% (p = 0.0015), respectively. The SEC 150-mg group in the MEASURE 2 trial exhibited an ASAS20 response in 66.7% of cases (p = 0.0063). The clinical response at 16 weeks in the patients randomized at baseline into SEC treatment groups was sustained for 52 weeks. The proportion of patients achieving ASAS20 response at 52 weeks was 63.2 and 68% in the MEASURE 1 trial (in the SEC 150- and 75-mg groups, respectively) and 73.3% in the MEASURE 2 trial (the SEC 150-mg group). At 52 weeks, ASAS40 reponse was achieved by 52.6% of the patients in the MEASURE 1 trial and by 60% of those in the MEASURE 2 trial (the SEC 150-mg group). In the MEASURE 1 trial, ASAS 5/6 response rates at 16 weeks were 42.1 and 52.0% in the SEC 150- and 75-mg groups (p = 0.0249 and p = 0.0013, respectively). In the MEASURE 2 trial, the proportion of the SEC 150-mg group patients achieving ASAS 5/6 response was 53.3% (p=0.0135). After 52 weeks, these rates were 57.9, 52, and 73.3%, respectively. The adverse reactions observed in both the placebo-controlled and later follow-up periods and in the Russian patient cohort suggest that SEC has an acceptable safety profile and good tolerability in patients with AC.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that most commonly occurs in women. Improved treatments for SLE have led to a substantial increase in the life expectancy of patients, so the problems of complications of both the disease itself and its therapy have come to be top priority. The most common complications of SLE among the musculoskeletal system lesions are osteoporosis and related vertebral compression fractures (VCFs). However, only one third of these fractures has clinical manifestations and causes the patient to seek medical advice. More VCFs remain undetected because they have no or scarce symptoms. The question of the influence of various factors (gender, age, menopause, etc.) on the incidence of VCFs in patients with SLE remains open. It should be expected that in postmenopausal women with SLE, the incidence of VCFs may be considerably higher than that in the population.

Objective: to determine the frequency of and to evaluate the role of various factors in the development of asymptomatic vertebral fractures in postmenopausal women with SLE (a retrospective study).

Subjects and methods. A total of 86 postmenopausal women (mean age, 59±7.9 years) with a diagnosis of SLE, which met the 2012 Systemic Lupus Collaborating Clinics (SLICC) criteria, were examined. The mean duration of the disease and menopause was 15±8.3 and 12.8±7 years, respectively. All the patients with SLE were treated with glucocorticoids (GC) at a dose of 15±5 mg/day calculated with reference to prednisolone for more than 12 months (mean, 159.7±90.9 months) and had a low disease activity (the mean SLEDAI-2K score was 5.1±3.9). The ACR damage index for SLE averaged 5.5±2.6. All the patients underwent vertebral fracture assessment (VFA) using a Hologic Explorer bone densitometer to identify VCFs in the thoracic and lumbar spine. The anterior, middle, and posterior heights of ТhIV–LV, and the height of each vertebra as well as the underlying vertebra were calculated and compared. If the differences in the anterior, middle, or posterior vertebral heights were >20–25%, this deformation was regarded as VCFs. Bone mineral density (BMD) in the hip and spine was measured with an X-ray bone densitometer.

Results. VFA revealed VCFs in 40 (46.5%) patients with SLE; these were detected for the first time in 22 (55%) patients since they had no significant clinical manifestations. VCFs happened most commonly in the mid-thoracic spine (ThVI–IX). All the patients with asymptomatic VCFs had a fracture of only one vertebra. The patients with VCFs had a longer duration of SLE and menopause, more frequently received cytostatic therapy, and had a higher cumulative dose and a longer duration of GC therapy. They also had a higher damage index and lower BMD values in LI–IV than patients without VCFs (p < 0.05). Neither SLE activity nor hip BMD was associated with VCFs (p > 0.05).

Conclusion. The detection rate for VCFs is nearly 50% in postmenopausal women with SLE, and about every two VCFs remain undetected. The long duration of SLE, menopause, and GC treatment, a high cumulative dose, a high damage index and low BMD values in LI–IV were associated with VCFs. VFA is an effective screening method to detect asymptomatic VCFs.

Objective: to estimate heart rate variability (HRV) in patients with systemic sclerosis (SS) and to investigate their relationship to echocardiographic structural and functional changes in the heart.

Subjects and methods. The investigation enrolled 125 patients with SS and 50 gender- and age-matched apparently healthy individuals who made up a control group. In addition to clinical examinations, 73 patients underwent HRV assessment from 24-hour Holter electrocardiogram (ECG) monitoring results and 121 patients had echocardiography (EchoCG). 24-hour Holter ECG monitoring was carried out in all control individuals.

Results and discussion. Examination of the main parameters of time-domain HRV in patients with SS revealed a significant decline in all temporal and spectral indices, except for the mean R–R interval duration (meanNN), as compared with the control group. EchoCG detected a variety of changes, primarily the induration and calcification of aortic and mitral valves in most patients. Left ventricular diastolic dysfunction was encountered in almost half of the patients with SS. Eight patients had a lower left ventricular ejection fraction (LVEF), which was <55%. Studying the association of HRV values with separate EchoCG parameters revealed significant inverse correlations of the mean standard deviation of R–R intervals in 5-minute recording segments during 24 hours with the thickness of the interventricular septum (r = -0.18; p < 0.05) and with the induration of the aortic valve (r = -0.18; p < 0.05); the square root mean squared of successive differences (RMSSD, ms) for R–R intervals and the percentage of adjacent R–R intervals that varied by more than 50 ms (pNN50) correlated with the induration of the aortic valve (r = -0.23; p<0.05 and r = -0.25; p < 0.05, respectively), with the presence of pericarditis (r = -0.24; p < 0.05 and r = -0,27; p < 0.05, respectively), and with the level of pulmonary artery systolic pressure (r = -0.23; p < 0.05 and r = -0.27; p < 0.05, respectively). There was also a direct correlation of rMSSD and pNN50 with LVEF (r = 0.27; p < 0.05 and r = 0.29, respectively; p < 0.05). A significant decrease in rMSSD and pNN50 was ascertained in hypertensive patients as compared to non-hypertensive patients (18.1±4.8 and 24.9±13.3; 2.3±1.8 and 5.7±6.5, respectively; p < 0.05).

Conclusion. Comprehensive examination using EchoCG and 24-hour Holter ECG monitoring revealed the high frequency and severity of significant cardiac changes in SS. The temporal spectrum analysis of HRV could confirm a significant reduction in the function of both the sympathetic and parasympathetic parts of the autonomic nervous system. Decreased HRV was associated with SS severity and activity, traditional cardiovascular risk factors, and cardiac structural changes.

The FAS antigen (Apo-1/CD95) is a key molecule of apoptosis in most cell types, including activated immune cells and fibroblasts. The FAS gene promoter region contains a single-nucleotide polymorphism (-670A/G) associated with a substitution of the nucleotide arginine for guanine, which is associated with the predisposition to systemic lupus erythematosus, multiple sclerosis, sarcoidosis, and autoimmune hepatitis.

Objective: to test the hypothesis that the FAS -670А/G polymorphism may predispose to systemic sclerosis (SS), its clinical and autoimmune phenotypes in a Russian patient sample.

Subjects and methods. The instigation enrolled 90 SS patients who were classified according to clinical and autoimmune phenotypes. A control group consisted of 152 apparently healthy unrelated individuals matched for sex and age. The FAS -670А/G polymorphism was studied by polymerase chain reaction, followed by restriction fragment length polymorphism analysis.

Results and discussion. A relatively small sample of Russian patients showed no statistically significant association of the studied FAS -670 A/G polymorphism with the predisposition to SS as a whole and the majority of its clinical and immunological phenotypes. There was a statistically significant positive association of the G allele (the FAS -670 GG+GA genotype) with the presence of digital ulcers and the chronic course of the disease. The G allele (the FAS -670 GG+ GA) was detected less frequently in patients with interstitial lung disease (ILD) than in those without ILD.

Conclusion. The findings show that the FAS -670A>G polymorphism plays a role in the predisposition to some clinical phenotypes of SS in Russian patients.

Objective: to evaluate the safety and efficiency of monotherapy with methotrexate (MTX) solution for subcutaneous injection (SC MTX), by using the estimated dosing, in patients with rheumatoid arthritis (RA).

Subjects and methods. A 12-month prospective controlled study enrolled 106 patients with early RA who were given SC MTX was conducted at the V.A. Nasonova Research Institute of Rheumatology in the framework of the REMARCA (Russian invEstigation of MethotrexAte and biologicals for eaRly aCtive Arthritis) program.

Results and discussion. 12-month SC MTX monotherapy could achieve the treatment goal (remission or low disease activity) in 68% of the patients with active RA who did not need biological agents (BAs). In 36% of the patients, the treatment caused adverse reactions (ARs) that were the basis for its complete discontinuation in 8%. The therapeutic effect of SC MTX depended on body mass index (BMI) and was more pronounced in patients with its normal values (≤25 kg/m2) than in those with overweight or obesity. The incidence of ARs did not depend on the duration of the disease and the weight of a patient receiving SC MTX. Addition of BAs to SC MTX monotherapy did not lead to an increase in the frequency of ARs. In early RA, the effect was better when SC MTX was used in combination with lowdose oral glucocorticoids. The findings showed the expediency of intensively using SC MTX at the doses calculated per 1 m2 of the body surface, the dependence of therapeutic action and the independence of the frequency and severity of ARs from the patient’s BMI.

Objective: to study the molecular mechanisms underlying the suppression of collagenase activity in the presence of deferoxamine (DFO) in articular cartilage explants from patients with osteoarthritis (OA).

Subjects and methods. The knee joint cartilage obtained during arthroplasty from 33 patients (mean age, 61.8±10.3 years) with OA, and that derived at autopsy from 25 people (mean age 40±6.1 years) without this disease were investigated. The cartilage was cultured in the presence of 10 μm DFO. The gene expression in the cartilage explants was determined by real-time reverse transcriptase and polymerase chain reaction.

Results and discussion. The reduced collagenase activity in the presence of DFO in the articular cartilage explants from patients with OA, which had been shown earlier, was accompanied by the significantly inhibited expression of matrix metalloproteinases 1 and 13 and cathepsin K, which had collagenase activity, as well as the marker of hypertrophic chondrocytes, such as X type collagen, and the proinflammatory cytokines interleukin-1β and tumor necrosis factor-α. DFO did not change the expression levels of the phosphoglucomutase and pyruvate kinase genes responsible for the production of adenosine triphosphate (ATP) during glycolysis and the glucose transporter Glut 1. On the contrary, the expression of the genes associated with ATP generation in the tricarboxylic acid cycle: isocitrate dehydrogenase, succinate dehydrogenase, α-ketoglutarate dehydrogenase, malate dehydrogenase, and adenosine monophosphate- activated protein kinase (AMPK) significantly increased. The expression of AMPK in the articular cartilage of patients with OA was significantly lower than that in healthy individuals.

Conclusion. Inhibition of collagen cleavage in the presence of DFO in the articular cartilage explants from OA patients, which was accompanied by a considerable decrease in the expression of the proteases responsible for degradation of the extracellular matrix, proinflammatory cytokines and chondrocytes hypertrophy, was due to the enhanced activity of mitochondrial oxidative phosphorylation in the chondrocytes.

Objective: to study the rates of primary disability due to musculoskeletal and connective tissue diseases (MSCTD) in the Irkutsk Region in 2013–2015 (in relation to age, gender, and urban or rural residence) and its nosological pattern.

Material and methods. A continuous method was used to analyze the database on the newly recognized as disabled due to MSCTD in the Irkutsk Region in 2013–2015. The rates were calculated per 10,000 adult population; the pattern was estimated as a percent.

Results and discussion. The rates of primary disability due to MSCTD in the Irkutsk Region were higher than those in the Russian Federation as a whole. Its reduction from 10.4 per 10,000 population in 2013 to 10.3 in 2014 and to 5.9 in 2015 was noted in the adults. Osteoarthritis headed the list of the causes of primary disability in the adults (45.5% in 2015) whereas dorsopathies did in the able-bodied (45.9% in 2015, 47.1% in 2014, and 48.2% in 2013). Osteoarthritis ranked first in the retirement-aged (61.5% in 2015, 75.1% in 2014, and 72% in 2013); it occupied the second place in the able-bodied (31.6% in 2015, 36.3% in 2014, and 38.2% in 2013). Rheumatoid arthritis was third among both the able-bodied and the retirement-aged. Higher disability rates were observed in the urban residents over all the years. The women became disabled more frequently than the men. In 2015, the primary disability rates among the men were 5.2, those among the women were 6.4 per 10,000 population; these were 9.2 and 19.4 and 8.4 and 12.1 in 2014 and 2013, respectively. The lower rates of disability due to MSCTD may be attributable to both the greater availability of high-quality and high-tech medical care for patients and the changes in normative documents on disability criteria.

An inflammatory response and the development of pain are interdependent processes. Inflammation accompanied by the overproduction of proinflammatory cytokines and mediators not only causes pain, but is also the main cause of its chronicity. Therefore, the use of anti-inflammatory drugs should be considered to be the mainstay of analgesic therapy. Part 2 of the review discusses the analgesic potential of various pharmacological groups that have an anti-inflammatory effect: nonsteroidal anti-inflammatory drugs, glucocorticoids, biological agents, methotrexate, slow-acting antiinflammatory drugs (chondroprotectors), as well as a number of promising and experimental agents, such as nerve growth factor inhibitors. It provides data from major clinical trials that have evaluated the analgesic effect of these drugs in various diseases and pathological conditions.

In recent years, more attention has been focused on Th17 cells that synthesize interleukin-17 (IL-17) in contrast to Th1 and Th2 cells, the marker cytokines of which are interferon-γ (IFN-γ) and IL-4, respectively. It is precisely these pathological activation and expansion of Th17 cells that are supposed to play a key role in the development of a wide spectrum of human immunoinflammatory diseases (IIDs), including rheumatoid arthritis (RA), psoriasis, ankylosing spondylitis (AS), psoriatic arthritis (PsA), inflammatory bowel disease, and systemic lupus erythematosus, which were previously considered as Th1-dependent diseases associated primarily with the hyperproduction of IL-2 and IFN-γ. This has served as a powerful stimulus to design new biological agents, the mechanism of action of which is based on blocking the pathological effects of IL-17, others associated with the activation of Th17 cells of cytokines, or small molecules interfering with transcription factors that regulate the synthesis of these cytokines. This review discusses current studies of the mechanisms regulating the formation and functional activity of IL-17 family cytokines, as well as evidence of the importance of these cytokines in the pathogenesis of IIDs. Special attention is paid to the clinical efficacy and safety of anti-IL-17A monoclonal antibody secukinumab used to treat psoriasis, PsA, AS, and RA.

The basis for the pathogenesis of systemic sclerosis (SS) is immune disorders that initiate inflammation, as well as vasculopathy with obvious microcirculatory disturbances, and generalized fibrosis. In SS, lung injury is due to an arterial lesion and/or a fibrotic process in the lung parenchyma and occurs as two major syndromes that are rarely concurrent in one patient; these are pulmonary arterial hypertension and interstitial lung disease (ILD). In SS, lung injury negatively affects the prognosis and ranks first among the causes of death. The review focuses on ILD, the most common injury of the respiratory tract in SS, which is detectable in 80% of patients, as evidenced by multislice spiral computed tomography (MSCT) of the chest. The histological manifestations are similar to those of idiopathic ILDs, but the histological type does not determine the prognosis. The course of ILD in SS is relatively benign, often subclinical. A severe progressive lesion develops only in 10–15% of cases. Clinically significant changes in the lung parenchyma develop early, within the first 3–5 years of the disease. Pulmonary functional tests show that relatively preserved and stable forced vital capacity is long recorded in the majority of patients, but the diffusing capacity of the lung is reduced in 70–80% of the patients. The values of pulmonary tests during the first examination are of prognostic value; the lower than normal they are, the worse the prognosis. Chest MSCT should be carried out in all patients with newly diagnosed SS, as the quantitative (prevalence) and qualitative (frosted glass, honeycomb lung) indicators affect the determination of therapy policy. ILD treatment is performed only in patients with obvious signs of progression, which are determined from the time course of changes in the decrease of values of pulmonary functional tests. Immunosuppressants, cyclophosphamide being the drug of choice, are used to treat ILD; biological agents, tocilizumab in particular, are currently being tested.

Ankylosing spondylitis (AS) is a chronic inflammatory disease from a group of spondyloarthritis (SpA), which is characterized by lesions of the sacroiliac joints and spine with the common involvement of entheses and peripheral joints in the pathological process. Advances in modern laboratory medicine have contributed to a substantial expansion of the range of pathogenetic, diagnostic, and prognostic biomarkers of AS. As of now, there are key pathogenetic biomarkers of AS (therapeutic targets), which include tumor necrosis factor-α (TNF-α), interleukin 17 (IL-17), and IL-23. Among the laboratory diagnostic and prognostic biomarkers, HLA-B27 and C-reactive protein are of the greatest value in clinical practice; the former for the early diagnosis of the disease and the latter for the assessment of disease activity, the risk of radiographic progression and the efficiency of therapy. Anti-CD74 antibodies are a new biomarker that has high sensitivity and specificity values in diagnosing axial SpA at an early stage. A number of laboratory biomarkers, including calprotectin, matrix metalloproteinase-3 (MMP-3), vascular endothelial growth factor, Dickkopf-1 (Dkk-1), and C-terminal telopeptide of type II collagen (CTX II) do not well reflect disease activity, but may predict progressive structural changes in the spine and sacroiliac joints in AS. Blood calprotectin level monitoring allows the effective prediction of a response to therapy with TNF inhibitors and anti-IL-17А monoclonal antibodies. The prospects for the laboratory diagnosis of AS are associated with the clinical validation of candidate biomarkers during large-scale prospective cohort studies and with a search for new proteomic, transcriptomic and genomic markers, by using innovative molecular and cellular technologies.

Systemic vasculitis (SV) associated with antineutrophil cytoplasmic antibodies (ANCA) is characterized by severe multiple organ lesions with a poor prognosis. The successful introduction of standard therapy with cyclophosphamide (CP) and innovative anti-B-cell therapy with rituximab (RTM) for the treatment of ANCA SV gives no grounds to stop further searching for effective and safe therapy since about 10–15% of patients with ANCA SV are refractory to standard therapy with CP; after the latter, approximately 40% of patients develop recurrences, and granulomatous inflammation in the respiratory organs in granulomatosis with polyangiitis (GPA) can be resistant to RTM treatment, especially following its single cycle. There is increasing evidence that the efficiency of anti-B-cell therapy can be enhanced by adding belimumab (BLM). The paper describes a clinical case of effective sequential combined anti-B-cell therapy with BLM and RTM for remission induction in a female patient who has GPA with severe granulomatous lung injury refractory to previous therapy with CP (a total dose of 6.2 g) and a single cycle of therapy with RTM (a total dose of 2.6 g). BLM was used 12 months after RTM administration because there were no positive changes in lung injury. At 12 months after initiations of treatment with BLM (800 mg twice at a weekly interval, then 800 mg monthly), there was a substantial reduction in the lung parenchymal foci, as evidenced by multislice spiral computed tomography (MSCT); and the treatment was continued for another 6 months, thereafter discontinued due to the occurrence of ulcerative stomatitis. After its relief, RTM was again given at reduced dose cycles of 500 mg every 6 months; lung MSCT showed further improvement and remission achieved. BLM may be effective in treating the GPA patients who are refractory to CP and have an insufficient response to RMT treatment. Combined anti-B-cell therapy aimed at depleting SD20+ B-cells and at blocking BAFF may be a promising area for the treatment of patients with ANCA SV.

The paper discusses the use of the recommended methotrexate doses for the treatment of rheumatoid arthritis in the randomized clinical comparative trials with biological agents.