According to the present-day views, autoimmunity is a complex pathological process, the essence of which is intolerance and hence a pathological immune response to intrinsic tissue components (autoantigens), which underlies the pathogenesis of a broad spectrum of human autoimmune diseases. Recently, diverse immune disorders underlying autoimmune rheumatic diseases (ARD) and syndromes have been revealed; an association has been found between the development of ARD and autoinflammatory diseases and syndromes; a classification of human immunoinflammatory diseases has been elaborated. The paper considers the results of the authors’ investigations of ARD treatment with innovative biologics, the pathogenetic mechanisms and diagnosis of ARD, by conducting immunological and molecular biological studies of a wide range of molecular and cellular biomarkers (autoantibodies, acute phase proteins, cytokines, chemokines, vascular endothelial activation markers, complement system components, lymphocyte subpopulations, bone and cartilage tissue metabolic products, genetic, epigenetic, transcriptomic markers), and approaches to personalized treatment of ARD.

Despite major advances in the management of rheumatoid arthritis (RA), whicare associated with the development of new methods for its early diagnosis, the clinical introduction of a wide range of innovative medications and particularly the improvement of a strategy for their use, glucocorticoids (GC) still remain the most important component of pharmacotherapy for this disease in real clinical practice. This publication that is a continuation of a series of papers devoted to the discussion of the main points of the 2013 European League against Rheumatism (EULAR) guidelines for the treatment of early RA, deals with the place of GC. An analysis of available data suggests that GC should be reserved for patients showing a high activity of the inflammatory process and having factors associated with a poor prognosis, but also, in the absence of risk factors for adverse events (AE), of course, contraindications to GC therapy. Throughout the use of GC, their AE should be meticulously monitored in compliance with the EULAR guidelines. It
is anticipated that the wider use of combined therapy with methotrexate and a GC in earlyRA will be able to improve its prognosis in at least some patients and to cause a substantial decrease in the burden of disease, by reducing the risk of disability and the needs for expensive biological agents and joint replacement. All this confirms that it is relevant to include the proposition for using GC into the 2014 Guidelines for the management of rheumatoid arthritis of the All-Russian public organization “Association of Rheumatologists of Russia”.

The diseases that are hazardous to the health of our planet's population and to the state of national economies should include psoriasis and psoriatic arthritis (PsA). This disease has been recorded in the official statistics of the Ministry of Health of Russia since only 2009. In 2011 in the Russian Federation as whole, the incidence of PsA, or arthropathic psoriasis (according to the International Classification of Diseases (ICD)), was 12.3 per 100,000 population or 5.7% of all registered psoriasis cases, which was substantially lowerthan that in other countries. Due to the lack of sufficient information on the epidemiology of PsA in the Russian population, the objective of this investigation was to study agerelated and regional trends in the incidence of this disease in the Russian Federation.

Material and methods. The incidence of PsA was analyzed using the data from annual statistical registered form No. 12 of the Ministry of Health of Russia over 2009–2013. The overall and primary morbidity rates of PsA among children and adults were analyzed in intensive values per 100,000 population. The prevalence of PsA and the rate of its incidence increment were analyzed in the Russian Federation's districts and subjects.

Results and discussion. The analysis showed a modest increase in overall morbidity rates of PsA in the Russia as a whole over the five years along with a decrease in the rates in the class as a whole. This suggests the disease severity that forces patients to seek medical advice. The situation associated with PsA morbidity among children and adults differs essentially in Russia's regions. The gap between in child and adult rates indicates that there are organizational problems in dermatovenereological care to the pediatric and adult populations in these regions. The alarming fact is that one-third of psoriatic patients experience joint pain and only 8% are diagnosed as having PsA, which also points to the inadequate diagnosis of this disease.The official statistical data on the incidence of PsA in the Russian Federation greatly differ from the results of international epidemiological surveys, which may be associated both with poor record keeping and diagnostic problems. The established situation may be improved by elaborating and introducing a diagnostic algorithm for PsA, by carrying out prophylactic examinations of psoriatic patients within mandatory health insurance in order to reveal the clinical signs of the disease, by timely examining the patients by a rheumatologist, and by creating the routing of the patients at all sociomedicalcare levels, and by simultaneously improving thesystem for the organizational recording of PsA cases in the country as a whole.

Objective: to evaluate the effect of a subcutaneous methotrexate (MT) formulation (methoject), on the structure and function of the vascular wall in patients with rheumatoid arthritis (RA).

Subjects and methods. A total of 94 RA patients who met the 1987 ACR or 2010 ACR/EULAR classification criteria and who were positive for IgM rheumatoid factor (RF) and/or anti-citrullinated peptide antibodies (ACPA) were examined. Carotid arteries were examined to assesslocal vascular wall stiffness, regional arterial stiffness and pulse wave velocity before and 12 months after start of MT therapy.

Results and discussion. The patients with RA were found to have subclinical great artery lesion manifesting itself as increases in common carotid artery (CCA) intima-media thickness (IMT) and stiffness index and as rises in peripheral augmentation index (AIp), stiffness index (SI), and reflection index (RI), the values of which correlated with the duration of RA, DAS28, the level of RF, and the concentration of ACPA. The use of MT in the patients with RA caused a statistically significant reduction in DAS28 and a decrease in CCA intima-media complex and local vascular (carotid) stiffness. More significant changes were observed when the duration of RA was less than 2 years; by the end of the follow up, this group showed a 29% decrease in CCA IMT (p < 0.01) and an average of 22.5% reduction in CCA stiffness (p < 0.05). 12-month MT therapy decreased AIp, SI, and RI valuesto a greater extent in the patients who had RA of less than 2 years; in this patient group, these parameters reached the reference values; in late RA, there were their average decreases by 1.7 (p < 0.01), 1.3 (p < 0.01), and 1.8 (p < 0.05) times, respectively.

Conclusion. MT therapy has vasoprotective activity, which is characterized by a reduction in the signs of CCA remodeling and regional stiffness in the vascular bed.

Rheumatoid arthritis (RA) frequently affects women of child-bearing age, which determines long-standing interest in studying the mutual impact of pregnancy and RA. The first observation described about 80 years ago has shown decrease of disease activity in the absolute majority of pregnant women. Later prospective studies have demonstrated that only 48–66% of women have clinical improvement during pregnancy, postpartum exacerbation of RA develops in 70% of cases, and most patients need drug therapy.

Objective: to assess changes of RA activity with DAS28-CRP during pregnancy and postpartum; to examine the impact of RA activity during early pregnancy on further course of the disease; and to determine drug therapy requirement in pregnant women with RA.

Subjects and methods. Thirty-two pregnancies were prospectively followed up during each trimester and within 12 months postpartum in 29 women with RA who fulfilled the 1987 ACR criteria and had been examined at the V.A. Nasonova Research Institute of Rheumatology from February 2011 to August 2014.

Results and discussion. 46% of the patients with RA showed reduction of disease activity during pregnancy. Exacerbation of RA was observed in 75% of the patients within 12 months at 1.5 months postpartum on average. In patients who were in remission and had low disease activity during early pregnancy, activity of RA throughout pregnancy and 1 month postpartum remained lower than that in those with moderate and high activity in the first trimester (p = 0.0008–0.04). A similar trend was also seen in patients without active arthritis at the moment of conception (according to survey data). In 23 (71.9%) patients with signs of disease activity during pregnancy, anti-inflammatory therapy was enhanced and DAS28-CRP decreased (p = 0.008) while it tended to increase in the remaining 9 (28.9%) patients with low disease activity who did not received medication. After delivery, patients with high and moderate disease activity showed earlier improvement (p = 0.008), as they more early resumed therapy with diseasemodifying antirheumatic drugs (DMARDs) and biologics than those who were in remission and had low disease activity during pregnancy. In the latter, a tendency for higher disease activity persisted for 3 months after delivery. Disease activity during the first-to-third trimester was significantly higher in 12 (37.5%) patients who had conceived while taking DMARDs or biologics and urgently withdrew them due to their pregnancy than in 20 (62.5%) cases when DMARDs and/or biologicalshad not been used or had been discontinued in advance when they started planning pregnancy (p < 0.04).

Conclusion. Remission or low activity of RA during early pregnancy is a predictor for low disease activity and for minimizing drug therapy to the point of its refusal throughout pregnancy. Without drug therapy, RA activity may tend to increase. A postpartum RA exacerbation is also noted in patients who have been in remission and had low RA activity antepartum. Dramatic withdrawal of DMARDs or biologics because of an unplanned pregnancy contributes to higher RA activity just in the first trimester of pregnancy. Pregnancy should be planned, by choosing stable anti-inflammatory
therapy in advance.

Objective: to assess progression of X-ray joint changes and their impact on functional status of patients with early rheumatoid arthritis (RA).

Subjects and methods. The investigation enrolled 204 patients with early RA included in the RADICAL (Early Arthritis: Diagnosis, Outcomes, Criteria, Active Treatment) program in the period 2003 to 2007. The duration of the disease at the inclusion was less than 2 years. RA was diagnosed according to 1987 American College of Rheumatology (ACR) criteria. Rheumatoid factor was presentin 67.5% of the patients and anti-cyclic citrullinated peptide antibodies – in 57%. Women were 86.5%; median age was 49 [40; 58] years. The patients received traditional diseasemodifying antirheumatic drugs and biological agents (24%). Therapy response was monitored applying the tight control strategy. Main clinical and laboratory parameters, DAS28, and HAQ scores, and functional class and hand and foot X-ray were recorded every year.

Results and discussion. After 5 years of follow-up, new erosions appeared in 57% of the patients. Joint erosions were present in 16.5% of the patients at the inclusion and in 73% following 5 years. At baseline, after 1, 2, 3, 4, and 5 years, the total erosion scores (modified Sharp score) was equal to 0 [0; 0], 0 [0; 1], 0 [0; 4], 1 [0; 8], 3 [0; 12], 6 [0; 14], respectively. A significant functional improvement could be achieved just during the first year of follow-up. Thus, the median HAQ value decreased from 1.125 [0.625; 1.75] to 0.5 [0.125; 1.0], reaching the population level. Following 2, 3, 4, and 5 years, the median HAQ was 0.5 [0; 1.0], 0.5 [0; 1.0], 0.5 [0; 1.0], and 0.75 [0.125; 1.125], respectively. There was a weak positive correlation between total erosion scores and HAQ in the eаrly stage of the disease. However, it became more marked after 3, 4, and 5 years (correlation coefficient, 0.38, 0.39, and 0.40,
respectively; p < 0.01). 

Conclusion.In spite of the stable pattern of disease course, structural damage progression was seen in patients with early RA. However, detailed erosive component assessment using the modified Sharp score showed that the structural changes were modest in the majority of patients and HAQ value during the first 4 years of follow-up were comparable with the population level, which may be indicative of a rather favorable functional prognosis. Five years later, there was an increasing correlation between total erosion scores and HAQ. This may be responsible for higher HAQ scores after 5 years of follow-up

Dynamic electroneurostimulation (DENS) is a type of percutaneous electroneurostimulation with a differentiation approach to choosing exposure areas and to optimizing electrocutaneous therapeutic action on the reflexogenic areas and acupuncture points for analgesia and for the treatment of functional disorders.

Objective: to study the clinical efficiency and safety of therapy using a DiaDENS-PC apparatus in the treatment of knee osteoarthritis (OA).

Subjects and methods. A multicenter randomized double-blind placebo-controlled study was conducted in 132 knee OA patients with pain value above 40 mm on visual analogue scale (VAS) and Lequesne’s index of 4–12. In a study group (n = 66), DENS was carried outwith a DiaDENS-PC apparatus using a trailing electrode applicator to the knee target in a Therapy stimulation mode at a frequency 77 Hz, a power of 15 units. In the placebo group, the similar procedure was performed with a switched-on placebo apparatus that did not differ in appearance from the working apparatus; but produced no electrical pulses. The treatment cycle consisted of 10 sessions lasting 30 min. Changes in Lequesne’s algofunctional index were primary end point. The results of the Get-Up to Go test (in seconds) and changes pain on VAS and WOMAC were used as secondary end points.

Results and discussion. Both groups showed a statistically significant reduction of painand improvement of Get-Up and to Go test results by the end of the treatment course (p < 0.0001). Therewas a statistically significant difference in pain in the compared groups after a treatment session during the first (p = 0.037) and second (p = 0.010) visits. The analgesic effect of therapy was observed to persist in the DENS group 2 weeks (p = 0.006) and 1 month (p = 0.070) after treatment termination. After 10 sessions, there was a statistically significant difference between the groups in the Get-Up and Go test (p = 0.033) and Lequesne’s index (p = 0.022). Both groups exhibited a significant decrease in the total WOMAC scores. In the DENS group, positive changes in all subscales were statistically significant starting from the second visit whereas in the control group, the total WOMAC scores improved

only at the expense of the pain subscale.

At present, the problem of infective endocarditis (IE) remains relevant for clinicians of different specialties, including rheumatologists. The distinctive feature of present-day IE is its polyetiological pattern due to a broad spectrum of pathogens. The lecture highlights in detail clinical picture of the disease, laboratory and instrumental findings. It presents current international diagnostic criteria for IE. The obvious clinical polymorphism, subtle symptoms, and monosyndromic onset as masks, all increases the significance of differential diagnosis of IE, in early disease stages in particular. Main approaches to differentiating IE from diseases posing the greatest differentially diagnostic challenges are set forth.

As of now, impaired immune homeostasis of the intestinal mucosa in genetically predisposed individuals is considered to be one of the major components in the pathogenesis of spondyloarthritis (SpA), which leads to systemic chronic inflammation. The results of recent studies may suggest that the interleukin-23/interleukin-17 (IL-23/IL-17) axis plays a leading role in the development of these diseases. The multifactorial components of the pathogenesis of SpA are characterized by not only the hyperproduction of IL-23, but also by the change in cell target susceptibility to this cytokine with aconcurrent increase in their number, resulting in the chronic autoinflammatory process that occurs via a wide spectrum of clinical manifestations of different types of SpA

The review deals with the prediction of the therapeutic effect of methotrexate in rheumatoid arthritis, by determining its level in the red blood cells.

The paper presents the clinical characteristics of Behcet's disease (BD) in Russian children, generally accepted criteria for BD, and diagnosis statement. The investigation is based on an observation of 17 children who met the international criteria for BD and were treated at the V.A. Nasonova Research Institute of Rheumatology in 2004 to 2013. One-third of children had a compromised family history; about 30% of the patients were ethnic Russian. The age at BD onset ranged from infancy to 16 years. The interval between disease onset and diagnosis was 1 to 10 years. The clinical symptoms at onset represented mostly frequently aphthous stomatitis and its accompanying fever and much less frequently aphthae of the genitalia. Furtherthe pathological process involved other organs and systems. In advanced stage of disease, there was already a clinical syndrome encompassing aphthous stomatitis, a genital ulcerative process, and lesions of the eye, skin, gastrointestinal tract, and less often central nervous system. The manifestations of the disease in different combinations can be concurrent with each other, showing a mosaic pattern. Treatment of children with BD included glucocorticoids, colchicine, azathioprine, and, if clinically indicated, tumor necrosis factor-α inhibitors. Their efficacy is discussed. The pediatric aspects of BD, which are presented in this paper, are first published in Russian medical press

Pachydermodactyly is a rare form of fibromatosis, which is characterized by an asymptomatic soft tissue enlargement around the proximal interphalangeal (PIP) joints of the hand. The etiology of the disease is unknown. Its possible triggers are recurrent minimal trauma, a habit or compulsive need to intertwine or rub the fingers. Spindle-shaped finger deformation with soft tissue thickening around the PIP joints mimics the clinical presentation of juvenile idiopathic arthritis (JIA). The distinctive features may be the absence of morning stiffness, contractures, pain, inflammatory and immunological changes in blood tests; however, it is the opinion of a number of authors that pachydermodactyly can be correctly diagnosed only after morphological examination. The paper gives the clinical manifestations of the disease and approaches to its diagnosis and differential diagnosis. It also describes the results of a retrospective study of 5 patients diagnosed as having pachydermodactyly. The final diagnosis was established after laboratory, instrumental, and morphological studies. Specific therapy has not been elaborated; however, by taking into account possible precipitating factors, excessive trauma of the affected finger bone should be avoided. The timely recognition of the disease allow to avoid administration of aggressive antirheumatic therapy required for JIA.

Prolonged hip arthritis in juvenile arthritis (JA) is a cause of serious joint destruction, leading to severe pain and functional disorders.

Objective: to assess the results of total hip arthroplasty (THA) in patients with JA. Subjects and methods. The investigation enrolled 20 women and 2 men. Their mean age at the time of surgery was 27.9 (18–49) years, mean weight – 47.7±2 kg. Mean height was 155.1 cm, which confirms growth retardation in these patients. The disease duration averaged 7.1 years. Mild protrusion of the acetabulum was stated in 9 (41%) and 13 (59%) patients, respectively.

Results and discussion. Functional status was assessed with Harris hip score (HHS), and Health Assessment Questionnaire (HAQ), pain – with visual analogue scale (VAS) quality of life (QL) – with EQ-5D before and 6–12 months after surgery. Six months after surgery, the mean EQ-5D score increased from 0.13 to 0.47 (ΔEQ-5D = 0.34;
р< 0.05), which corresponded to a moderate clinical response in QL. Only after 12 months of follow-up, there was a pronounced effect of surgical treatment: the EQ-5D index increased up to 0.64 (ΔEQ-5D = 0.51; p< 0.05). On the average, HAQ decreased from 2.016 to 1.429 after 6 months and to 1.159 after 12 months, which was suggestive of a significant clinical improvement. Functional status also improved according to HHS: at 6 months, it was assessed as good (HHS, 80-89) in 3 (13.6%) patients; satisfactory – in 9 (40.9%), and 10 (45.5%) patients had HHS below 70; at 12 months, it was excellent (HHS, 90–100) in 4 (18.2%), good (80–89) – in 4 (18.2%), satisfactory – in 8 (36.4%) and 6 (27.2%) patients had HHS lower than 70. Preoperatively, pain on VAS averaged 65.4 mm; 6 and 12 months following surgery, it reduced to 41.6 and 36.3 mm, respectively. 

Conclusion. THA in patients with JA significantly improves the function of the affected hip joint and QL. It is also important to note that THA promotes social adaptation – three patients have entered higher educational establishments and two more patients have got married and given birth to healthy babies.

Objective: to investigate the efficacy of an anti-BlyS drug (belimumab) for the treatment of systemic lupus erythematous (SLE).

Subjects and methods. Belimumab (BLM) was administered to three patients with SLE (two women and one man were aged 24, 28, and 39 years, respectively). SLE activity was estimated according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K, the values of which were 8, 12, and 14 scores, respectively, due to high immunological activity, skin, joint, and mucosal lesions. The high Systemic Lupus International Collaborating Clinics (SLICC) Damage Index score of 3 was found in 2 of the 3 patients. All patients received glucocorticoids (GC) 20–25 mg/day; two – hydroxychloroquine and one – mycophenolate mofetil 1000 mg/day. Therapy with BLM was performed using a standard scheme: three 10 mg/kg infusions during the first month, then one infusion every month.

Results. Positive clinical changes were noted 2 months after therapy initiation; symptoms completely disappeared 3 and 6 months later. Anti-DNA antibodies and complement fractions, the levels of which were partially normalized at 2 to 9 months of treatment, were most refractory to BLM therapy. During the follow-up, there were no SLE exacerbations; the dose of GC could be halved in two cases. Glomerular filtration normalized in one patient with inactive lupus nephritis.

Conclusion. BLM treatment is justified in patients with moderate SLE activity in the presence of polyarthritis, serositis, skin and mucosal lesions and with high immunological activity. The use of BLM is not contraindicated in patients with inactive lupus nephritis without obvious kidney dysfunction. The additional motivation to use BLM may be an inadequately high GC dose, a recurrent disease course, insufficient therapeutic efficiency, and a risk for irreversible
organ damages

The new Treat-to-Target (T2T) strategy in the treatment of early psoriatic arthritis (PsA) is aimed at achieving remission or low disease activity. As of now, the new biological agent ustekinumb (UST), anti-interleukin (IL) 12/23 monoclonal antibodies, was used to treat psoriasis and PsA. The paper presents clinical observations of the efficacy of UST in early PsA treated according T2T strategy. The described clinical cases demonstrate that use of UST 45 mg both alone and in combination with methotrexate for early PsA with moderate and high activity reduced manifestations of peripheral arthritis and psoriasis, promoting rapid achievement of remission or minimal disease activity. Overall, UST is well tolerated by the patients.

There is much evidence that ankylosing spondylitis (AS) is a disease that is also much older than early human civilizations and man as a whole. Until now, the Russia's earliest (14th c ntury) archaeological finding of such a patient remains a Volga Bulgaria inhabitant suffering with AS during his life. In the Republic of Tatarstan, at the site of an ancient Bulgar settlement appearing in the early ninth century, archaeologists have discovered an unusual grave: the deceased sitting with his back against the western wall of a tomb pitand having a bronze crosslet under his fingers. According to a historical source, it was the way of burying Christian hierarchs as pastors sitting on the altar and anticipating the great assize during which the destinies of human souls should be ruled. Anthropological analysis showed that the bones belonged to a 35–45-year-old man who was 158–163 cm tall. During the examination of the remains,
attention was called to the following features of the spinal structure: ankylosis of the inferior cervical and superior thoracic vertebrae (СV–ThI) and inferior thoracic and lumbar spine (ThIV–LII) predominantly due to ossification of the anterior longitudinal ligament. Facet vertebral joints and costotransverse joints were also ankylosed at the same levels. The man's neck was fixed in a bent-over position with the head down, the chin touching the breast bone – the socalled soliciting posture. By and large, the vertebral changes are characteristic of late (X-ray stage III) spondylitis. Spinal and pelvic photos and X-films are given for demonstration. The studies conducted by historical scientists and forensic medical experts suggest that the found remains are most likely to belong to Christian Theodore nicknamed Jerusaleman, also further known as Holy Theodore philosopher Kamsky (Bulgarian), who was mentioned in the Nikon chronicle in 1323.

The paper discusses whether it is expedient to use the standards approved by the editorial staff of a number of medical journals for original articles on the therapeutic effect of drugs, including antirheumatic agents since this is of importance for the analysis of their safety.