Recently, more attention has been given to Th17 cells, the pathological activation of which plays a leading role in the development of a wide spectrum of human immunoinflammatory diseases (IID), including rheumatoid arthritis, psoriasis, ankylosing spondylitis, psoriatic arthritis, inflammatory bowel diseases, etc. This has served as an incentive to design new biological agents and small molecules, the main mechanism of action of which is based on blocking the pathological effects of interleukin-17 (IL-17), others are associated with the activation of Th17 cells cytokines or signaling pathways that regulate the effects of these cytokines. The review discusses current ideas about the mechanisms regulating the formation and functional activity of IL-17 family cytokines, as well as evidence for the importance of these cytokines in the pathogenesis of IID.

The paper presents the design, general characteristics of and possibilities of data usage from the All-Russian register of patients with psoriatic arthritis (PsA).
The purpose of creating and introducing the register into Russian healthcare practice is to evaluate the effectiveness of the diagnosis and treatment of PsA. The All-Russian register of PsA patients was created for the period 2016–2018 within the framework of the All-Russian register of patients with arthritis «OREL» on the basis of the V.A. Nasonova Research Institute of Rheumatology and with the support of the All-Russian public organization «Association of Rheumatologists of Russia». This system is an all-Russian population-based register that allows for the recording and monitoring of patients with PsA throughout the follow-up period. This enables healthcare specialists and organizers to obtain reliable information on the state of care for this category of patients in the region.

The main purpose of the register is to provide necessary information support and automated technology for solving the problems of accounting, controlling, and monitoring of the status of PsA patients and to organize information interaction between specialists. The register is based on existing state regulatory legal acts. While developing and testing of the register, there were a number of tasks to be solved: to evaluate the efficiency of existing standard and promising targeted PsA therapies in real practice; to assess and improve the routing of patients with PsA. The use of the register allows an operational analysis of the following characteristics: demographic and socioeconomic parameters of patients with PsA; anamnestic data of patients with this condition; results of clinical examinations, instrumental and laboratory data.
The geography of the register covers 27 regions of the Russian Federation; the register includes information on 460 patients with PsA.
Creating a register permits one to track the dynamics of various parameters (social, demographic, and medical ones), to compare treatment options and the clinical and functional characteristics of patients with PsA, and to evaluate their performance, disability and changes in the social and labor status during the treatment performed. 
Thus, for the first time in the Russian Federation, the demographic, functional, and socioeconomic parameters of patients with PsA were comprehensively analyzed and the level of performance and impaired daily activities in PsA patients were studied using the WPAI questionnaire; moreover, the patients’ functional and psychological status was evaluated for the first time, by applying the PsAID-12, FACIT questionnaires (in the patients of the V.A. Nasonova Research Institute of Rheumatology).
An analysis of the information available in the register makes it possible to compare the efficiency of different PsA treatment regimens, by estimating the rates of remission and/or minimal disease activity in real practice.

Treatment adherence in patients with osteoporosis (OP) is rather low throughout the world, and 50 to 75% of patients stop taking anti-osteoporotic drugs within a year after therapy prescription.
Objective: to establish determinants that affect patient adherence to OP therapy.
Subjects and methods. The investigation enrolled 150 women older than 50 years (mean age, 68.8±9.4 years) with OP duration of ≥3 years who had made an outpatient visit to the V.A. Nasonova Research Institute of Rheumatology. Their examination consisted of a survey using a specially designed questionnaire. Treatment adherence was evaluated, by using the data on the duration of treatment for OP within 3 years prior to the study inclusion, as well as by calculating the drug use index.
Results and discussion. During 3 years, 94 (63%) female patients were adherent to OP treatment, including those who took zoledronic acid (78%), denosumab (75%), and alendronate or ibandronate (60%); therapy with antiosteoporotic drugs was changed in 53% of patients. The most common reason for missing or discontinuing treatment was poor drug tolerance (33%); and that for self-replacement of recommended drugs was their cost (75%). Age, education, marital status, income, duration of disease and length of treatment, a familial history of fractures or a hip fracture, the number of concomitant diseases, and the total number of drugs taken did not affect medication adherence. Patients who were more adherent to OP treatment were those who underwent determination of serum vitamin D levels (p=0.009), calculation of a 10-year absolute osteoporotic fracture risk according to the FRAX® algorithm (p=0.022), an annual bone densitometry examination (p=0.0158) and, more often than annually, biochemical blood tests (p=0.0043), as well as those who had visited their physician 3 times or more during the estimated period (p=0.003). There were more people adherent to OP treatment among the patients receiving the parenteral formulations of drugs than among those who took drugs as tablets (p=0.036). Educational materials, brochures, and lectures on OP and a follow-up in a specialized center did not ensure that treatment adherence could be significantly increased (p>0.05).
Conclusion. Patient adherence to OP therapy is positively influenced by determination of serum vitamin D levels, calculation of a 10-year absolute osteoporotic fracture risk (FRAX®), annual therapeutic monitoring using bone densitometry and results of biochemical blood tests, regular visits to a physician  who follows up the patient for OP, as well as simplification of a dosing regimen and administration of the parenteral formulations of drugs used to treat OP.

Objective: to assess changes in health-related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE) during performed therapy.
Subjects and methods. The investigation included 128 patients with reliable SLE who fulfilled the 2012 SLICC criteria. Sixty-eight patients received standard therapy; 60 used biological agents (BA). During the first visit and at 12 months, all the patients were assessed for disease activity using by SLEDAI-2K and for organ damage employing the SLICC damage index (DI). HRQoL was assessed by the LupusQoL questionnaire that was filled out by the patients independently.
Results and discussion. At Visit 1, the disease activity index averaged 8.0±7.3 in the standard therapy group and 15.4±7.6 in the BA group (p≤0.001); DI was 1.2±0.9 and 1.8±1.8, respectively (p=0.008). BA-treated patients had significantly lower HRQoL scores on all questionnaire scales, except «dependence on others» and «emotional health» ones Both the standard therapy and BA groups showed significantly lower disease activity during Visit 2 at 12 months. HRQoL assessment revealed significant improvements in the scales «pain», «planning», «intimate relationships», «emotional health», «body image», and «fatigue» in the BA group. The standard therapy group had a statistically significant improvement in the scale «dependence on others». All the other scales of the questionnaire displayed a positive change in HRQoL; however, it did not reach statistical significance.

Rheumatoid arthritis (RA) is the second most common rheumatic disease. In recent decades, there has been an active search for and study of biologically active substances involved in the pathogenesis of RA, which can serve as a starting point in designing new drugs for targeted therapy of this disease. The hepatokine fetuin-A (FA) is one of these substances.
Objective: to investigate serum FA levels in patients with RA.
Subjects and methods. The investigation enrolled 110 patients with RA. All the patients underwent the following set of studies: general blood test and determination of the serum levels of C-reactive protein (CRP), serum FA, rheumatoid factor, anti-cyclic citrullinated peptide (anti-CCP) antibodies, cartilage degradation products (CartiLaps), and urine creatinine. A control group consisted of 30 apparently healthy individuals whose serum FA level was determined in order to obtain reference values.
Results and discussion. The normal FA level varied from 653.55 to 972.19 μg/ml. All the patients with RA were divided into two groups: 1) 23 patients with a low FA level (<653.55 μg/ml) and 2) 87 patients with a normal FA levels (≥653.55 μg/ml). The groups differed significantly in anti-CCP antibody concentrations, disease activity, radiological stages, functional classes, and the presence of complications. Patients with lower FA levels were noted to have increased CRP concentrations, erythrocyte sedimentation rate, and CartiLaps/urine creatinine ratio. The mean FA concentration was considerably and significantly lower in patients with higher DAS28 scores. 
Conclusion. Our investigation has revealed that there is a relationship between the levels of FA and the individual clinical manifestations of RA. The lower FA level is associated with higher disease activity and the aggressive phenotype of RA (the presence of anti-CCP antibodies, radiological stages III and IV, extra-articular manifestations and complications).

Objective: to study the clinical and laboratory features of patients with anticentromere antibody (ACA) positive Sjö gren’s syndrome (SjS); to assess the spectrum of autoantibodies in patients of this group; to determine the frequency with which the SjS patients who are highly positive for ACA, meet the international classification criteria for SjS and systemic sclerosis (SS); to reveal the incidence of MALT lymphomas in this patient group; to estimate the incidence of primary biliary cirrhosis (PBC)/biliary lesions as part of autoimmune epithelitis in SjS in this patient group.

Material and methods. A total of 83 patients with ACA positive SjS were comprehensively examined at the V.A. Nasonova Research Institute of Rheumatology during the period 2012 to 2018. The inclusion criteria were con formity to the 2001 Russian SjS criteria and a high ACA level. MALT lymphomas were diagnosed on the basis of histological and immunohistochemical studies and polymerase chain reaction-based determination of B-cell clonality in the biopsy samples of affected organs according to the World Health Organization classification of Hematopoietic Tumors. The diagnosis of PBC/biliary lesions was made on the basis of histological and immunohistochemical studies of liver biopsy specimens.

Results and discussion. The investigation revealed low detection rates for anti-Ro antibodies (32.5%), anti-La antibodies (7.2%) and rheumatoid factor (RF) (21.7%), which were typical for the classical SjS immunophenotype), increased ESR (14%), leukopenia (7%), hypergammaglobulinemia (17.6%), elevated levels of IgG (9.5%) and IgA (18.7%), and hypocomplementemia (16.1%) in the ACA positive SjS patients. Despite the low detection rate of RF, 15 (18%) patients in this group developed MALT lymphomas: 14 patients had salivary gland MALT lymphoma and one patient had tonsil MALT lymphoma with peripheral lymph node involvement (generalized marginal zone lymphoma). Also, the patients of this group showed high detection rates for AMA antibodies (34.6%), increased IgM level (29.7%) and a higher risk for PBC/biliary lesions as a manifestation of autoimmune epithelitis in SjS (14.5%). AMA-antibodies were absent in only two patients who were diagnosed with liver disease according to biopsy specimens. Nervous system and renal lesions, antiphospholipid syndrome, rheumatoid arthritis, hypergammaglobulinemic purpura, and cryoglobulinemic vasculitis were much less common and sporadic. Also ACA-positive SjS patients often have Raynaud’s phenomenon (54.9%) with scleroderma-type capillaroscopic changes (68%) and a limited form of SS (24%) according to the 2013 ACR criteria.

Conclusion. ACA-positive SjS is a subtype of the disease, which is significantly different from the classic one in a number of clinical and laboratory signs and characterized by an increased risk for SS, MALT lymphomas, and PBC/biliary lesions as a manifestation of autoimmune epithelitis in SjS which in some cases leads to the underdiagnosis of SjS. ACA should be considered as pathogenetically related to SjS autoantibodies; and all patients who are seropositive for ACA should be examined for SjS and PBC/biliary lesions as a manifestation of autoimmune epithelitis in SjS regardless of whether they have SS or not, as well as complaints of dry mouth and eyes. Patients with significantly enlarged salivary glands should undergo biopsy to rule out or confirm MALT lymphoma before initiating hormonal, antilymphoproliferative, and anti-B-cell therapy.

Currently, there have been a small number of works on differences between males and females with axial spondyloarthritis (axSpA) and there have been no studies estimating a gender difference in radiographic sacroiliitis progression in axSpA.
Objective: to compare the main clinical manifestations of sacroiliitis and its radiological progression in axSpA in men and women over time during a 2-year follow-up period.
Subjects and methods. The investigation was conducted using the Moscow cohort from the early SpondyloArthritis (CoRSAr) study, which currently consisted of 175 patients. The analysis included 68 patients followed up for ≥2 years. Their mean age at the time of inclusion in the cohort was 28.5±5.8 years; the mean disease duration was 24.1±15.4 months. 92.6% of patients were HLA-B27-positive.
Results and discussion. Among the 68 patients followed up over 2 years, there were 33 (48.5%) men and 35 (51.5%) women. At baseline, the females were older than the males (p<0.01), while the disease duration was the same and averaged about 2 years. Among the males, there were more patients with ankylosing spondylitis (AS) than those among the females (75.5 and 42.8%, respectively; p<0.05), and the men had a higher total score of radiological sacroiliitis (tsrSI) than the women. The level of C-reactive protein (CRP) was also higher in the men than in the women (12.8 and 4.3 mg/l, respectively; p<0.05). Two years later, AS was present in 90.9% of the males and in 60.0% of the females (p<0.05).
Conclusion. Women fall ill with axSpA later than men, and the latter are more frequently observed to have HLA-B27, higher tsrSI and elevated CRP levels. Progression from non-radiological axSpa to AS was more common in men.

Objective: to investigate the effect of endothelial dysfunction, catecholamines, and renin on the diurnal blood pressure (BP) profile in patients with systemic sclerosis (SS).
Subjects and methods. Twenty-five patients with SS underwent determination of the blood count of desquamated endotheliocytes by the method described by J. Hladovec (1978), the plasma levels of endothelin-1 (ET-1), adrenaline, norepinephrine, and renin by enzyme immunoassay. All the patients underwent 24-hour BP monitoring with calculating the time index, daily index, the magnitude and rate of a morning rise in BP, as well as its daily variability.
Results and discussion. Hypertension was detected in 8 (32%) patients with SS. All the patients with SS showed signs of endothelial dysfunction, as evidenced by considerable differences in endothelial activation measures compared with the control group: the mean level of ET-1 was 5.8±2.3 and 0.48±0.21 fmol/ml (p<0.05); the number of desquamated endotheliocytes was 4.50 [3.00; 7.00] and 2.10 [1.00; 3.20] • 104/l, respectively (p<0.05). The levels of adrenaline and norepinephrine in SS were significantly higher than those in the control. There were positive correlations between endothelial dysfunction and the degree of an increase in BP. Endothelial dysfunction was found to have a negative impact on the diurnal BP profile in the presence of pathological types of night-peaker and non-dipper. 
Conclusion. Two mechanisms, such as endothelial dysfunction and sympathoadrenal activation, are responsible for the pathogenesis of clinical symptoms of SS, including hypertension.

Immunoinflammatory rheumatic diseases (IIRDs) are a large group of pathological conditions with impaired immunological tolerance to autogenous tissues, leading to inflammation and irreversible organ damage. The review discusses current ideas on the role of type I interferons in the immunopathogenesis of IIRDs, primarily systemic lupus erythematosus, and new possibilities for personalized therapy.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects any organs and systems and is characterized by a wide range of various clinical manifestations. According to the treat-to-target strategy for SLE, in addition to monitoring disease activity and irreversible organ damage, it is necessary to assess health-related quality of life (HRQOL), which enables one to obtain a complete and objective description of the patient. All the factors and problems that may worsen HRQOL should be also taken into account. Fatigue, pain, and depression are identified as the major symptoms that largely affect HRQOL. The impact of cognitive impairment associated with the disease is also considered. Impaired body image, i.e. the perception of his own appearance by a patient himself, is an important problem in patients with SLE. The unpredictable course of the disease and the impaired physical functioning of patients make it difficult to perform everyday activities, as well as disturb socialization; the patients often experience of being dependent on others. Due to SLE, the patients are often limited in their choice of profession or forced to quit/change their jobs, which leads to financial losses and feelings of social isolation. The review also considers gender, age, and education as factors influencing HRQOL in patients with SLE.

Etodolac is a nonsteroidal anti-inflammatory drug (NSAID), a moderately selective cyclooxygenase-2 inhibitor, which has been already used in clinical practice for more than 30 years as a universal analgesic and anti-inflammatory agent. Etodolac has proven itself in relieving acute pain associated with injuries and surgical interventions (particularly in dentistry). However, the main point of application of etodolac is long-term pain control in chronic rheumatic diseases, such as osteoarthritis and rheumatoid arthritis. Numerous clinical trials have shown that etodolac is at least not inferior in its therapeutic effect to many other popular representatives of the NSAID group or exceeds them. The main advantage of etodolac is the low frequency of gastrointestinal complications. This review presents the basic data available in the literature on the efficacy and safety of etodolac.

Coexisting hip osteoarthritis (OA) and lumbar spinal stenosis (central and foraminal) and/or spondylolisthesis is called a hip-spine syndrome (HSS). The central problem is correctly diagnosing and determining the tactics of surgical or medical treatment for patients with HSS. The paper describes a clinical case of a female patient with HSS and an examination algorithm for determining the significance of peripheral neuropathy and hip OA and discusses the choice of surgical treatment tactics.

The diagnosis of a disease accompanied by febrile syndrome presents special problems in clinical practice. The traditional diagnostic algorithm in this case involves the exclusion of infections, cancer, and rheumatic diseases. The causes of fever can be severe types of rheumatoid arthritis, systemic vasculitis, and diffuse connective tissue diseases, as well as rare diseases, the difficulty of diagnosis of which is due to low awareness of the disease and the absence of specific clinical, laboratory, and instrumental signs. These also include relapsing polychondritis (RPC) in particular. RPC is a rare systemic inflammatory disease of cartilage tissue, which leads to its structural changes resulting in complete destruction. Cartilages of the acoustic apparatus, nose, trachea, and joints are mainly affected. The severity of cardiovascular injury in RPC has recently been emphasized. This disease is observed with equal frequency in men and women, primarily at the age of 40–60 years, predominantly in white people, but it also occurs in other populations. The etiology of RPC is unknown. There are no pathognomonic laboratory and instrumental tests for the diagnosis of RPC. A unified approach to treating this condition has not been elaborated. The available data on the pathogenesis, various clinical manifestations and treatment options of the disease are analyzed. The authors’ own observations of RPC are depicted.

Blockade of interleukin-6 (IL-6) is one of the most promising areas in the treatment of a number of immunoinflammatory diseases. Tocilizumab (TCZ), the first registered anti-IL-6 receptor monoclonal antibody, has been used effectively by rheumatologists since 2010. During this period, the spectrum of adverse reactions (ARs) of TCZ has been clearly defined. However, the multifaceted biological effects of IL-6 determine the probability of unexpected ARs. The article describes a clinical case of drug-induced encephalopathy with cognitive dysfunction during TCZ therapy.