A sonographic sign, such as linear hyperechoic inclusions or uric acid deposits in the hyaline cartilage, has been recently introduced into the system of gout classification criteria. At the same time, the differential diagnostic value of this sign in early gouty arthritis (GA) has not been adequately explored.

Objective: to evaluate specificity and sensitivity for detecting linear hyperechoic inclusions in the differential diagnosis of early GA in comparison with the increased level of uric acid, the presence of subcutaneous tophi, and the identification of intraosseous cysts at radiography.

Subjects and methods. The investigators analyzed the data of examining 119 patients with arthritis with its symptom duration within 6 months at the stage of differential diagnosis. The following diagnoses were further established: GA in 32 patients, osteoarthritis (OA) in 28, rheumatoid arthritis (RA) in 28, and psoriatic arthritis (PsA) in 16. Along with clinical, laboratory, and radiological examinations, all the patients underwent ultrasonography (USG) of inflamed joints with an 18-MHz linear transducer to identify linear hyperechoic inclusions (urate deposits) in the hyaline cartilage.

Results and discussion. Joint USG revealed urate deposits in 28 (87.5%) patients with GA, in 3 (10.7%) with OA, and in 1 (6.3%) with PsA. The sensitivity of the other signs of gout in early GA was 21.7% for intraosseous cysts, 25.0% for subcutaneous tophi, and 81.3% for hyperuricemia. The specificity of USG for urate deposits in GA was 94.4% and was comparable with that for the other signs of gout (86.1–98.6%). Conclusion. USG detection of urate deposits in patients with gout is characterized by high sensitivity and specificity for diagnosing GA within the first 6 months after the initial symptoms appear. 

Exudative or proliferative processes accompanied by joint destruction may predominate in the synovial membrane (SM) in different stages of rheumatoid arthritis (RA). The features of SM changes should be considered in the early diagnosis of RA and in the development of combination treatment for this disease.

Objective: to study arthroscopic SM changes in patients with different RA durations and different blood anti-cyclic citrullinated peptide (anti-CCP) antibody levels.

Subjects and methods. 37 patients with RA underwent arthroscopy with an arthroscope of a 2.4-mm diameter and 30° angle (Karl Storz GmbH, Germany). RA duration was <2 years in 17 patients and ranged from 2 to 8 years in 20; the blood level of anti-CCP antibodies did not exceed 60 IU/ml in 15 patients and it was higher in 22. SM changes were assessed by a semiquantitative method.

Results and discussion. Arthroscopy revealed a preponderance of SM hyperemia with an increased vascular pattern (p<0.01) and fibrin deposits (p<0.05) in patients with a RA duration of < 2 years and that of villous hyperplasia with the formation of club-shaped villi (p<0.05) in those with a RA duration of >2 years. The increase in anti-CCP by >60 U/ml was associated with a predominance of inflammatory hyperplasia (p < 0.01), SM hyperemia with a pronounced vascular pattern (p<0.05), as well as with the presence of pannus (pp<0.01).

Objective: to analyze the relationship of the count of FoxP3+ T regulatory cells (Tregs) to the clinical and laboratory parameters of disease activity and the levels of antibodies in a group of patients with early rheumatoid arthritis (RA).

Subjects and methods. The investigation enrolled 45 patients with early RA (2010 ACR/EULAR criteria) who had not previously received treatment with methotrexate, including 39 women; median age was 52.0 [32.5; 57.5] years; disease duration, 5 [4; 6] months, DAS28 5.01 [4.18; 5.8]; 71.1% of the patients were rheumatoid factor (RF) positive and 88.9% were anti-cyclic citrullinated peptide positive. The relative and absolute counts of Treg (FoxP3+CD25+; CD152+surface; CD152+intracellular; FoxP3+CD127-; CD25+CD127-; FoxP3+ICOS+; FoxP3+CD154+; FoxP3+CD274+) were measured by immunofluorescence staining and multicolor flow cytometry. A control group consisted of 20 healthy donors who were matched for sex and age with the examined patients.

Results and discussion. DАS28 was high, moderate, and low in 22 (48.9%), 20 (44.4%), and 3 (6.7%) patients, respectively. As compared with the healthy donors, the patients with early RA were observed to have lower values in the percentage of FoxP3+CD25+ cells, in the percentage and absolute count of FoxP3+ICOS+ cells, in the percentage and absolute count of FoxP3+CD154+ and FoxP3+ CD274+ T cells; p<0.05 in all cases. Negative correlation was recorded between the percentage of FoxP3+CD25+ and C-reactive protein (CRP) (r=-0.4); that of CD152+intracellular and DAS28 (r=-0.35), ESR (r=-0.46), CRP (r=-0.54); that of FoxP3+CD127 and CRP (r=-0.42); that of CD25+CD127 and DAS28 (r=-0.38), SDAI (r=-0.41), CDAI (r=-0.36), ESR (r=-0.39), CRP (r=-0.47); p<0.05 in all cases.

The patients who were seronegative for RF were found to have higher values in the percentage of CD25+CD127, in the percentage and absolute count of Foxp3+CD154+ and Foxp3+CD274+ T lymphocytes.

Objective: to study the baseline level and time course of changes in peripheral blood B cell subpopulations in patients with systemic lupus erythematosus (SLE) versus the clinical manifestations of the disease during therapy with rituximab (RTM) and belimumab (BLM).

Subjects and methods. 49 patients with a documented diagnosis of SLE and high and moderate SLEDAI-2K values were divided into three groups: 1) 40 patients received RTM, 2) 5 patients took BLM; 3) 4 patients had combination therapy (dual anti-B-cell therapy) with RTM + BLM. Peripheral blood B lymphocyte subpopulations were measured by multicolor flow cytometry using a panel of monoclonal antibodies against surface membrane markers of B lymphocytes; the patients underwent clinical immunological examination before therapy with biological agents and every 3 months during a year.

Results and discussion. Patients with high SLE activity (SLEDAI-2K 18±5) and involvement of vital organs had generally higher levels of double negative memory cells (r = 0.52; p < 0.001) with relatively low counts of naive B cells (r=-0.54; p < 0.0007) than those without severe organ pathology (SLEDAI-2K 8±2). RTM therapy at 3 month of follow-up resulted in a noticeable decrease in the number of naive and double negative memory B cells and to a lesser extent in that of non-switched and switched memory B cell. A rapid recovery of the count of memory B cells and plasmablasts after a RTM cycle at 6 months after therapy initiation should be evaluated as a predictor of early exacerbation of SLE. There was a reduction in the clinical and laboratory signs of SLE activity, as well as inhibition of naive B cells, plasma cells, and plasmablasts in all the 5 patients receiving BLM at various stages of follow-up. Dual anti-B cell therapy most effectively reduced disease activity at 3 months, prolonged the achieved remission, contributed to the achievement and maintenance of a low B lymphocyte level at later stages of control, to the further decline in the number of plasmablasts and plasma cells, and prevented the synthesis of autoantibodies.

Conclusion. Assessment of the time course of changes in peripheral blood B lymphocyte subpopulations provides new opportunities to identify impaired function and regulation of cellular immunity in patients with SLE, it may be a useful diagnostic parameter to monitor an autoimmune disease and a valuable tool to assess and predict a response. 

Objective: to evaluate the efficacy and tolerability of denosumab and adherence to treatment with this drug in women with postmenopausal osteoporosis (OP) during a three-year prospective study under the conditions of routine clinical practice

Subjects and methods. The investigation included 48 women (mean age 65.2±9.1 years) with postmenopausal OP; the patients were recruited in April 2013 to March 2014. All the patients underwent densitometry of three regions and determination of the levels of calcium, creatinine, and alkaline phosphatase over time and vitamin D at inclusion into the study. Adverse events were recorded every 6 months.

Results and discussion. 92% of the patients received denosumab during a year, 81.25 and 66.7% – for two and three years, respectively. In 5 (10.4%) women with a low fracture risk according to the FRAX®, during the treatment their bone mineral density (BMD) reached the level seen with osteopenia or normal levels; and the patients were switched to use only calcium and vitamin D. After 3 years, there were significant BMD increases in the lumbar spine by 8.54%, in the femoral neck by 4.77%, in the entire proximal femur by 5.65%, and in the distal forearm by 1.99%. The prior use of other antiosteoporotic drugs did not reduce the efficiency of denosumab treatment. There was no clinical fractures during a 3-year follow-up. Compliance with dosage regimen was observed in 90.6% of the women who completed the three-year follow-up. Age, marital status, education level, time taken to reach a clinic, parental hip fractures, a history of fractures, duration of OP, and previous treatment did not influence treatment adherence.

Conclusion. The three-year prospective follow-up in real clinical practice has shown that denosumab is an effective and safe agent to treat patients with postmenopausal OP. 

Objective: to investigate the impact of VDR and MCP-1 gene polymorphisms on the efficiency of 12-month therapy with strontium ranelate (SR) in women with postmenopausal osteoporosis (OP).

Subjects and methods. The investigation enrolled 34 postmenopausal women (mean age 65±8 years), who was diagnosed with OP by lumbar spine and/or proximal femur examinations using a Hologic QDR 4500W X-ray bone densitometer. The gene polymorphisms of VDR (BsmI) and MCP-1 (-2518A/G) were genotyped by polymerase chain reaction, followed by restriction fragment length polymorphism analysis.

Results and discussion. The carriers of the BB and Вb genotypes of the VDR gene had a statistically significantly lower increase in the bone mineral density (BMD) of the lumbar spine than those of the homozygous recessive bb genotype (p = 0.024 and p = 0.022, respectively) and the bb genotype and the BB+Bb genotype (p = 0.004), and the carriers of the GА genotype of MCP-1 gene had a statistically significantly lower increase in the BMD of the entire proximal femur than those of the homozygous AA genotype (0.2±2.5% and 4.4±4.4%, respectively; p = 0.004) at 12 months after SR treatment.

Conclusion. The findings may suggest that the BB and Bb genotypes of the VDR gene and the GA genotype of the MCP-1 gene may negatively affect the efficacy of SR in patients with OP. However, additional studies on a larger sample of patients, including those with other forms of OP, are required to confirm this assumption. 

The lecture gives an update on adult-onset Still's disease, including that on the specific features of the clinical picture and treatment of this disease. 

The review considers new data on the immunopathology of rheumatoid arthritis (RA), with emphasis on the early stage of the disease. The evolution of RA includes several successive (or discrete) stages that culminate in the development of a symptom complex characteristic of RA. However, the nature of the interaction of environmental factors, genetic predisposition, and immune mechanisms that determine the transition from stage to stage, the types of progression, the nature and severity of extra-articular (systemic) manifestations, and the risk of comorbid diseases is not entirely clear and is currently the subject of intensive studies. Hyperproduction of autoantibodies, such as rheumatoid factors and antibodies to proteins subject to posttranslational modification, citrullination, carbamylation, acetylation, etc., occupies an important place among the pathogenetic mechanisms of RA development. Immune response against posttranslationally modified (primarily citrullinated) proteins is a key pathogenetic mechanism for the development of RA in all stages of the disease. New data on the role of anti-citrillinated protein antibodies (anti-CPA) in the development of pain and bone resorption in the absence of inflammation pathogenetically substantiate the existence of a preclinical disease phase characterized by arthralgia and autoantibody hyperproduction. In conclusion, the paper considers the new possibilities of preventing RA in high-risk groups (anti-CRA-positive clinically suspect arthralgia), by using methotrexate, the anti-B cell drug rituximab, the T-lymphocyte costimulation blocker abatacept, etc. 

Rheumatoid arthritis (RA) is the most common and severe chronic joint inflammatory disease leading to early disability and shorter lifespan in patients. A number of studies have demonstrated that short-term and long-term prognosis of the disease is much more favorable in achieving remission in the early stages of the disease; however, the efficacy of drugs varies widely from patient to patient, which is due to the heterogeneity of the disease itself and to a number of other causes. In this connection, the problem of searching for biomarkers that allow the personalized choice of a treatment regimen in each specific case remains relevant as before.

Rituximab (RTM) that is a chimeric monoclonal antibodies against CD20 membrane antigen of B cells causing the depletion of various B lymphocyte subpopulations is one of the effective and safe drugs used to treat RA. Compared to other biological agents, RTM has a long-term efficacy of one treatment cycle, which persists for 6 months or more. The current literature presents a large amount of data on the role of cellular and molecular biomarkers in predicting the efficiency of RTM therapy for RA, some of which are considered in this review. 

Atherosclerosis and its complications are the major cause of late mortality among patients with systemic lupus erythematosus (SLE). SLE and coronary heart disease share common pathophysiological mechanisms associated with systemic and chronic inflammation. At the same time, traditional risk factors, such as hypertension, elderly age, smoking, hypercholesterolemia, obesity, and male sex, cannot fully explain the mechanism for the accelerated development of atherosclerosis in patients with SLE. Specific risk factors, such as its duration, glucocorticoid use, anti-doublestranded (native) DNA autoantibodies and antiphospholipid antibodies, create conditions for the accelerated development of atherosclerosis in this group of patients.

The available facts indicate that a rheumatologist can reduce the risk of cardiovascular disease (CVD), by controlling the activity of SLE. Traditional CVD risk factors should be also modified with smoking cessation, weight loss, and blood pressure control. It is necessary to keep in mind the role of anti-inflammatory therapy, in particular the positive effect of drugs, such as anti-malarial drugs and mycophenolate mofetil, and the adverse prognostic effect of prolonged glucocorticoid use. Further studies should assist in elaborating effective risk scales and specific therapeutic programs for the prevention and treatment of CVD in patients with SLE. 

Abnormalities in the blood cholesterol transport system play a leading role in the development of atherosclerotic vascular lesions in rheumatoid arthritis (RA). The article analyzes the lipid profile in patients with untreated RA. It gives data on the impact of inflammation on proatherogenic lipid and lipoprotein metabolic disturbances and defines the need to explore high-density lipoprotein subfractions and their functions, namely, reverse cholesterol transport in patients with RA as a more promising method for assessing cardiovascular risk. 

The paper discusses the specific features of using nonsteroidal anti-inflammatory drugs in patients with high cardiovascular risk. 

The paper discusses the results of the long-term PRECISION study specially designed for the prospective comparative evaluation primarily of the cardiovascular safety of celecoxib, ibuprofen, and naproxen, which are long used for the treatment of pain in patients with arthritis. 

Vladimir Iosifovich Konenkov.