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Rheumatology Science and Practice

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Vol 56, No 6 (2018)
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FRONTIERS

685-691 1501
Abstract
The paper considers the modern concepts of the etiology and pathogenesis of psoriatic arthritis (PsA). The latter is currently indicated as a T-cell-mediated disease that is based on the activation of cellular immunity, followed by the hyperproduction and imbalance of key pro- and anti-inflammatory cytokines, such as tumor necrosis factor-α (TNF- α), interleukin-1β (IL-1β), IL-6, IL-12/23, and IL-17. The paper presents the basic principles of diagnosis and clinical manifestations of the disease and notes the importance of screening questionnaires, the use of which allows specialists to diagnose PsA early, by actively identifying articular complaints, the characteristic clinical and radiological signs of damage to the joint, spine, and entheses. It is pointed out that the key target of pharmacotherapy for PsA is to achieve remission or minimal activity of the main clinical manifestations of the disease, to slow down or prevent its radiographic progression, to increase the length and quality of life in patients, and to reduce the risk of comorbidities. The authors characterize the major groups of used drugs: nonsteroidal anti-inflammatory drugs, conventional and targeted synthetic disease-modifying antirheumatic drugs, and biological drugs (inhibitors of TNF-α, IL-12/23, and IL-17). The key Treat-to-target principles of patient management are considered; it is noted that strict control over disease activity and treatment results provides suppression of all major clinical manifestations of PsA. The paper also shows the basic principles of the creation and further development of the All-Russian Registry of PsA patients, which makes it possible to optimize management decision-making on the provision of high-tech medical care and drugs for this cohort of patients.

ORIGINAL RESEARCH

692-696 1216
Abstract

Objective: to determine risk factors (RFs) for venous thromboembolic events (VTE) in patients with rheumatoid arthritis (RA).
Subjects and methods: The investigation enrolled 374 patients (311 women and 63 men) with a reliable diagnosis of RA who met the 2010 ACR/EULAR classification criteria. The patients' mean age was 53.7±13.6 years; the disease duration was 12.1±10.7 years. All the patients were treated at the V.A. Nasonova Research Institute of Rheumatology Clinic during the period from 2014 to 2017. A standard clinical examination of the peripheral joints was performed. RA activity was measured using DAS28. A survey was made using a questionnaire including questions on traditional RFs for VTE and RFs that might be caused by RA and its therapy.
Results and discussion. VTE were recorded in 45 (12%) out of the 374 patients. Group 1 included 45 patients with VTE; Group 2 consisted of 329 patients without VTE. Multidimensional analysis showed an increased risk of developing VTE in RA under the influence of the following factors: high inflammatory activity; lower extremity varicose veins; hypercholesterolemia; and hypertension. Their weighted coefficients were 1.1, 2.5, 1.0, and 0.9, respectively. According to the obtained model (p<0.001), the risk of VTE in RA can be predicted by the following formula: Z = 1.1 • high RA activity (Yes = 1/No = 0) + 2.5 • lower extremity varicose veins (Yes = 1/No = 0) + 1.0 • hypercholesterolemia (Yes = 1/No = 0) + 0.9 • hypertension (Yes = 1 / No = 0).
Conclusion: The increased risk for VTE in RA patients determines the need for its timely assessment, by taking into account the known risk factors as both standard ones and those caused by the disease itself and its therapy. This risk assessment is necessary for the timely adequate treatment and prevention of thrombotic events in RA.

697-702 1193
Abstract

Objective: to clarify the relationship of adiponectin and leptin to the signs of disease activity and the levels of pro- and anti-inflammatory cytokines in patients with early rheumatoid arthritis (RA).
Subjects and methods. The investigation enrolled 27 RA patients who met the 2010 ACR/EULAR classification criteria and had never received glucocorticoids (GCs) or disease-modifying antirheumatic drugs. The median age of the patients was 56 [46; 64] years; the duration of the disease was 8 [6; 15] months. All the patients had moderate or high RA activity according to DAS28. The majority of the patients were seropositive for rheumatoid factor (88.9%) or anticyclic citrullinated peptide antibodies (96.3%). A control group included 30 gender-, age-, and body mass index (BMI)-matched people without inflammatory arthritis. Enzyme immunoassay was used to estimate the concentrations of adiponectin and leptin; XMAP multiplex assay was applied to measure the levels of interleukin-1β (IL-1β), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17 and macrophage inflammation proteins (MIP), such as MIP-1α and MIP-1β.
Results and discussion. In RA patients, adiponectin concentrations were higher (p<0.001) and leptin levels and leptin/adiponectin (L/A) ratios were lower than those in the controls (p=0.04 and p<0.001, respectively). In RA, there were direct correlations of leptin levels with concentration of IL-17 (r=0.4; p=0.03), IL-4 (r=0.39; p=0.04) and erythrocyte sedimentation rate (ESR) (r=0.3; p=0.05), as well as relationships of L/A ratios to ESR (r=0.38; p=0.05) and the levels of CRP (r=0.4; p=0.04) and MIP-1β (r=0.55; p=0.03). An increase in adiponectin concentrations was associated with a decrease in MIP-1β levels (r=-0.63; p<0.01). In patients with BMI ≥25 kg/m2, leptin concentrations were comparable in RA patients and controls (p=0.1); the differences in adiponectin levels and L/A ratios remained in both cases (p<0.001). This subgroup of patients with RA showed significant correlations between leptin and IL-17 levels (r=0.52; p=0.03), adiponectin and MIP-1β concentrations (r=-0.59; p=0.01), L/A ratios and MIP-1β levels (r=0.55; p=0.02).
Conclusion. In early RA, there was a lower leptin synthesis and a higher adiponectin production. The correlations between the levels of adipocytokines, IL-17, and MIP1β, on the one hand, suggest that adipose tissue has an impact on systemic inflammation and, on the other, confirm that proinflammatory cytokines are involved in the development of insulin resistance and obesity.

703-708 1111
Abstract

Objective: to evaluate the clinical efficacy of the rituximab biosimilar Acellbia® at a dose of 600 mg intravenously at a 2-week interval in patients with active rheumatoid arthritis (RA) 12 and 24 weeks after initiation of treatment.
Subjects and methods. Examinations were made in 20 active seropositive RA patients who had not been previously treated with biological agents (BAs), but received two infusions of the rituximab biosimilar Acellbia® at a dose of 600 mg intravenously at a 2-week interval during stable therapy with methotrexate (MT) and glucocorticoids (GCs). The European League Against Rheumatism (EULAR) response criteria (Disease Activity Score 28 (DAS28), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index) and the American College of Rheumatology (ACR) criteria were used to evaluate the efficiency of Acellbia® therapy. Disease remission was identified by DAS28 and 2011 ACR/EULAR criteria. The safety profile (the frequency of all reported adverse events) corresponds to the data on the safety of rituximab (MabThera®).
Results and discussion. At the time of inclusion, median DAS28 was 5.6 [4.9; 6.8], SDAI – 27.1 [23.0; 39.9], and CDAI – 26.6 [22.2; 37.0]. At week 12 after initiation of Acellbia® therapy, they decreased to 4.2 [3.24; 4.75], 14.4 [8.5; 20.7], and 13.2 [7.9; 19.0] respectively, which remained at 24-week follow-up (p<0.01). At week 12, the frequencies of ACR 20%, 50%, 70% improvements were 70, 55, and 5%; at week 24, these were 75, 45, and 15%, respectively. A good or moderate EULAR response at week 24 was observed in 25 and 60% of patients, respectively. At week 24, DAS28, SDAI, and CDAI remissions were achieved by 4 (20%), 2 (10%), and 1 (5%); low disease activity – by 4 (20%), 5 (25%), and 6 (30%) patients, respectively; high disease activity as measured by SDAI and CDAI remained in 3 (15%) patients. Two patients (10%) met the 2011 ACR/EULAR remission criteria at 24 weeks.
Conclusion. The rituximab biosimilar Acellbia® 600 mg used in patients with active seropositive RA is clinically effective and comparable in the safety profile as shown in investigations of the brand-name MabThera® (F. Hoffman-La Roche Ltd., Switzerland) at a low dose (500 mg), as well as the first BA.

709-715 1563
Abstract

As of now, there has been a great body of data on the use of rituximab (RTM) in systemic sclerosis (SS), mainly on its positive effect on skin fibrosis and lung injury. However, information is still scarce about the effect of RTM on other organs and systems, namely the heart affected by SS.
Objective: to assess the time course of changes in the signs of heart involvement in SS patients one year after initiation of RTM therapy.
Subjects and methods. The paper gives data on changes in cardiac disorders in 71 patients with SS one year after the prescription of RTM.
Results and discussion. The rate of cardiac rhythm and conduction disorders and diastolic dysfunction was unchanged. At the same time, a significant increase in left ventricular ejection fraction (EF) and a reduction in the severity of dyspnea was achieved, which correlated with improved lung function (a significant rise in forced vital capacity). The results of treatment in three patients with predominant heart involvement associated with SS (coronary heart disease and hypertension were ruled out) were considered in detail. These patients displayed pronounced positive changes as increased EF, less severe cardiac arrhythmias, reduced chronic heart failure, better quality of life, as well as the synchronicity of lower disease activity, less skin induction, improved lung function, and stabilized pulmonary artery systolic pressure.
Conclusion. RTM in combination with traditional therapy can be considered as a potentially effective drug for the treatment of heart involvement in SS.

716-721 998
Abstract

Coxitis is one of the most common extra-axial manifestations of ankylosing spondylitis (AS). Most Russian studies consider hip joint (HJ) involvement in AS patients as a major factor of poor prognosis in this disease. All detected hip joint changes are characterized by one term «coxitis». Until recently, there has been no clarity on inflammation of which structures of HJ leads to its destruction. This problem can be solved by prospective studies. A start was made by the V.A. Nasonova Research Institute of Rheumatology on the study of the evolution of coxitis in AS in 2013. This communication is devoted to the results initially identified by various imaging techniques for detecting HJ changes.
Objective: to study the characteristics of HJ injury in AS, which have been detected by different imaging techniques.
Subjects and methods. The investigation enrolled 125 AS patients, including 84 men (a male/female ratio of 2:1). The mean age of the patients was 31.4±9.1 years; the mean age at disease onset – 24.6±4.4 years; the median duration of AS at the time of examination – 96 (12–444) months. The HLA-B27 antigen was present in the majority of patients (94%). AS activity defined by ASDAS-CRP and BASDAI was high; BASFI scores averaged 3.4±2.1. All the patients underwent the following instrumental examinations: plain pelvis radiography, HJ ultrasound and magnetic resonance imaging (MRI).

Results and discussion. The clinical, ultrasound, and MRI signs of coxitis were found in 82, 75, and 88% of cases, respectively; coxitis was radiologically confirmed only in 50% of patients. This disease was diagnosed by several techniques in the vast majority of cases. The diagnosis of coxitis was based only on clinical signs in only three (2%) patients. In approximately every sixth (16%) patients with AS, who had clinical signs of coxitis, the latter was verified only by one of the instrumental techniques (ultrasonography, radiography, or MRI). Our findings demonstrated that more than half of patients had high coxitis activity, and more prolonged coxitis was responsible for higher X-ray HJ changes and functional limitations.
Conclusion. Our study has showed that the instrumental techniques used to diagnose coxitis are not equivalent in evaluating HJ injury. To decide which of them is more effective in screening and predicting the course of coxitis, there is a need for further prospective investigations.

722-726 3651
Abstract

Objective: to evaluate the efficacy and safety of a selective phosphodiesterase type 4 inhibitor in patients with psoriasis and psoriatic arthritis (PsA).
Subjects and methods. An open uncontrolled study was conducted, which enrolled 20 patients (12 men, 8 women); their mean age was 39.2±14.3 years, the mean duration of psoriasis and PsA was 20.2±12.2 and 10.4±10.2 years, respectively. All the patients included in the study had previously received phototherapy, systemic drugs (methotrexate, aromatic retinoids) with an insufficient effect. Apremilast was administered according to the standard regimen: dose titration during the first 5 days, then 30-mg tablets twice daily for 26 weeks. The efficiency of the therapy was evaluated from changes in PASI, BSA, and sPGA and according to the American College of Rheumatology (ACR) criteria at 14 and 26 weeks and from those in DAS28 at 26 week.
Results and discussion. There were 50 and 75% decreases in PASI respectively in 12 (60%) and 5 (25%) patients, at week 14 of therapy and in 14 (70%) and 7 (35%) patients at week 26. Fourteen (81.2%) patients achieved 20% ACR improvement at week 14. DAS28 decreased on an average by 1.8 at week 26. Adverse events (severe headache, tachycardia) were observed in two patients who were excluded from the study.
Conclusion. Apremilast is an effective and safe agent for the treatment of psoriasis and PsA in patients who have received another systemic therapy proven to be ineffective or they tolerated the latter poorly.

727-730 998
Abstract

Hip joint (HJ) inflammation in ankylosing spondylitis (AS) is a frequent manifestation and an unfavorable prognostic feature of the disease and it requires total hip arthroplasty in 7–8% of patients. Nonsteroidal anti-inflammatory drugs (NSAIDs), sulfasalazine (SSZ), and tumor necrosis factor-α inhibitors are used to treat AS-associated coxitis. However, the influence of these treatments on the time course of HJ structural changes has not been currently studied.
Objective: to estimate the time course of HJ changes clinical, X-ray, and ultrasonographic examination was performed in AS patients receiving various drugs: NSAIDs, SSZ, and adalimumab (ADA) during 12 months.
Subjects and methods. Seventy-eight AS patients who had clinical, ultrasonographic, and radiological signs of HJ inflammation were followed up. The patients were divided into three groups: 1) 25 patients who took NSAIDs daily; 2) 26 patients who received NSAIDs and SSZ in a daily dose of 2–3 g; 3) 27 patients who were treated with NSAIDs and subcutaneous injections of ADA 40 mg once every 2 weeks. In addition to conventional clinical and laboratory investigations, all the patients underwent radiography with Bath Ankylosing Spondylitis Radiology HIP Index (BASRI-Hip) estimation and HJ ultrasonography.
Results and discussion. In Group 2, 12-month SSZ use led to a reduction in median pain intensity during HJ movements on a visual analog scale (VAS) from 26.1 [13.9; 42.7] to 69.3 [56.8; 79.3] mm (p<0.05), CRP levels from 4.4 [1.5; 6.9] to 15.2 [8.3; 21.8] mg/l (p<0.05), and synovial membrane thickness from 6.7 [5.8; 8.5] to 9.6 [7.9; 11.8] mm (p<0.05) compared to the basic data. In Group 3, ADA administration resulted in pain reduction from 14.2 [5.2; 26.7] to 72.1 [65.3; 89.1] mm (p<0.05), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) from 1.7 [1.1; 3.1] and 1.4 [1.1; 2.2] to 7.5 [5.9; 8.6] and 3.1 [2.6; 3.9], respectively (p<0.05), CRP levels from 2.7 [0.2; 5.8] to 24.3 [17.4; 35.9] mg/l (p<0.05), and HJ synovial membrane thickness from 6.3 [5.0; 7.7] to 9.9 [8.1; 12.6] mm (p<0.05). SSZ and ADA did not substantially affect the time course of changes in BASRI-Hip and the process of new osteophyte formation in HJ.
Conclusion. The use of SSZ and ADA in the complex treatment of patients with AS-associated coxitis leads to a lower HJ synovitis activity.

731-738 1580
Abstract

The clinical efficacy and safety of interleukin-6 (IL-6) receptor blockade have been well studied, but the data on the impact of therapeutic inhibition of IL-6 on B cells are scarce and contradictory. Preliminary reports have shown that B cell function and a humoral immune response may be modulated by an IL-6 receptor inhibitor.
Objective: to assess the effect of 12-month tocilizumab (TCZ) therapy on B-cell phenotype and gene expression in RA and to analyze the association between B-cell subsets and RA activity.
Subjects and methods. Examinations were made in 24 active RA patients (20 women and 4 men) (median age, 55 [49; 64] years; disease duration, 72 [24; 108] months; DAS28 5.8 [5.3; 6.3]; the patients were seropositive for rheumatoid factor (RF) (100%) and for anti-cyclic citrullinated peptide antibodies (87.3%). The patients received TCZ 8 mg/kg every 4 weeks. After 12 months of therapy, 54% of patients were categorized as good responders, 46% as moderate responders according to the EULAR response criteria. A control group consisted of 29 volunteers (21 women and 8 men; median age, 58.5 [53.0; 62.0] years). Peripheral blood lymphocytes were immunophenotyped at the time of enrollment and after 12 months. The absolute and relative counts of CD19+B lymphocytes, memory B cells (CD19+CD27+), non-switched memory B cells (CD19+IgD+CD27+), switched memory B cells (CD19+IgDCD27+), naive (CD19+IgD+CD27-), double-negative (CD19+IgD-CD27-), transitional (CD19+IgD+CD10+CD38++CD27) B cells, plasma cells (CD19+СD38+), and plasmablasts (CD19+СD38+++IgD-CD27+CD20-) were estimated using multicolor flow cytometry.
Results and discussion. The relative and absolute counts of memory B cells (CD19+CD27+) (1.3 [0.9; 1.7]%, 0015 [0.001; 0.003]•109/l), switched memory B cells (CD19+IgD-CD27+) (6.8 [3.6; 11.6]%, 0.01 [0.005; 0.02]•109/l), and the absolute number of transitional B cells (CD19+CD38++CD10+IgD+CD27-) (0.00009 [0; 0.00028]•109/l) were found to be lower in RA patients than in donors: 2.2 [1.1; 3.0]%, 0.003 [0.001; 0.007]•109/l; 12.8 [9.3; 17.0]%, 0.02 [0.01; 0.04]•109/l; 0.0001 [0; 0.0003]•109/l, respectively (p<0.05 for all cases). After 12 months of TCZ therapy initiation, there were decreases in the relative and absolute counts of plasmablasts (CD19+CD38+++CD27+IgD-CD20-) from 0.15 [0.1; 0.3] to 0.1 [0.01; 0.1]% and from 0.0003 [0.00007; 0.004]•109/l to 0.0001 [0; 0.0003]•109/l, respectively (p<0.05). At the same time, the relative and absolute counts of memory B cells (CD19+CD27+) and switched memory B cells (CD19+CD27+IgD-) remained lower in RA patients than in donors: 1.0 [0.7; 1.2] and 2.2 [1.1; 3.0]%; 0.001 [0.006; 0.003]•109/l and 0.003 [0.001; 0.007]•109/l; 3.1 [1.1; 4.2] and 12.8 [9.3; 17.0]%; 0.003 [0.002; 0.006]•109/l and 0.02 [0.01; 0.04]•109/l, respectively (p<0.05 for all cases). Following 12 months of TCZ therapy, the numbers of other B-cell subpopulations were not considerably altered. When included in the study, the patients with RA showed correlations between the absolute count of memory B cells (CD19+CD27+) and the level of C-reactive protein (r=0.50; p<0.05); between the absolute count of plasmablasts (CD19+CD38+++CD27+IgD-CD20-) and the level of RF (r=0.41 and r=0.52; p<0.05). There were no correlations of B cell subsets with clinical and laboratory findings after 12 months of TCZ initiation.
Conclusion. Immunophenotyping of peripheral blood B lymphocyte subsets showed the lower relative and absolute counts of memory B cells (CD19+CD27+) and switched memory B cells (CD19+CD27+IgD-) in RA patients than in healthy donors. The found correlations between the counts of memory B cells and plasmablasts and the values of laboratory parameters in patients with high RA activity may suggest that B lymphocytes are involved in the pathogenesis of RA. There was a decline in plasmablast levels after 12 months of TCZ therapy.

739-745 1187
Abstract

The current Treat-to-target (T2T) strategy in the management of patients with psoriatic arthritis (PsA) is based on strict control over the dynamics of a patient's status and timely correction of therapy according to the presence or absence of remission or minimal disease activity (MDA) within 6 months after treatment initiation. The multidimensional RAPID3 questionnaire based on the patient's own opinion of his/her health status, has demonstrated its high effectiveness in assessing remission in patients with rheumatoid arthritis (RA). The possibilities of using the RAPID3 questionnaire in patients with early PsA (ePsA) with T2T strategy have not yet been studied.
Objective: to investigate whether the multi-dimensional RAPID3 questionnaire may be used to assess the achievement of remission and MDA in ePsA patients with a T2T (Treat-to-target) strategy
Subjects and methods. The investigation enrolled 61 patients (29 men and 32 women) with ePsA meeting the 2006 CASPAR criteria; the mean age of the patients was 37±10.6 years; the duration of PsA and psoriasis was 11.3±10.2 and 75.4±80.9 months, respectively. The patients were followed up for 12 months during the open-label REMARCA study performed by the T2T principles. At baseline, all the patients were given methotrexate (MTX; Methoject) subcutaneously at a dose of 10 mg/week, with escalation by 5 mg every 2 weeks up to 20–25 mg/week. If there was no low disease activity (LDA), DAS28/DAS remission, or MDA after 3 months, the patients received combined therapy with MTX 20–25 mg/week and adalimumab (ADA) or ustekinumab (UST) at standard doses. All the patients underwent standard rheumatologic examination before therapy and every 3 months. The investigators calculated tender joint count (TJC) among 78 joints; swollen joint count (SJC) among 76 joints, the Ritchie articular index, and the number of entheses by the Leeds Enthesitis index (LEI). Joint pain measurement, patient (PGA) and physician (PhGA) global assessment on visual analog scale (VAS) was performed, the serum level of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were evaluated. DAS and DAS28, HAQ and RAPID3 functional index were estimated. The number of patients achieving LDA, DAS/DAS28 remission, and MDA were determined.
Results and discussion. At 1 year of therapy, 36 (59%) out of the 61 patients and 25 (41%) out of the 61 patients were treated with MTX and this drug in combination with ADA or UST, respectively. After 1 year of treatment, the whole group displayed a significant improvement of all PsA activity parameters as compared with baseline values: DAS, 3.93 [3.20; 4.58] / 1.36 [0.82; 2.25], SJC, 7 [5; 11] / 1 [0; 3], TJC, 8 [6; 1] / 1 [0; 3], PhGA, 56 [48; 69] / 10 [5; 20] and VAS pain, 54 [48; 68] / 11 [1; 20], PGA, 55 [49; 68] / 14 [7; 24], HAQ, 0.75 [0.50; 1] / 0 [0; 0.63], respectively. There was a significant correlation of RAPID3 with PsA activity and CRP. MDA was seen in 43 (70.5%) out of the 61 patients. Among the patients who had achieved MDA, the RAPID3 values corresponded to remission, but were significantly higher in the patients who had not attained MDA: 2.5 [1.3; 5.3] and 8.1 [6.0; 15.1], respectively. RAPID3 demonstrated high sensitivity in assessing the achievement of remission, LDA, and MDA in patients with ePsA.
Conclusion. RAPID3 based on a patient's personal opinion of his/her disease is a simple and reliable tool to assess the disease activity in patients with ePsA and to monitor the efficiency of therapy with a T2T strategy and may be really useful in practice.

POSTGRADUATE PROGRAM OF CONTINUING MEDICAL EDUCATION

746-752 992
Abstract
The paper considers currently available drugs used to treat calcium pyrophosphate crystal deposition disease. It discusses the advantages and disadvantages of the most widely used drugs, such as  nonsteroidal anti-inflammatory drugs, colchicine, glucocorticoids, traditional immunosuppressants, as well as prospects for the use of biologic agents.

PROGRESS IN RHEUMATOLOGY IN THE XXI CENTURY

753-759 810
Abstract
At present, the role of the renin-angiotensin system (RAS) in regulating the cardiovascular system and maintaining water and electrolyte homeostasis has been well studied. However, over the past decades, new components of the RAS have been identified, suggesting a wider range of its potential effects on the body. It is of fundamentally importance for rheumatologists to affect inflammation, including rheumatoid inflammation, through blockade of angiotensin (AT) II formation via the effects of AT 1–7 and angiotensin-converting enzyme inhibitors, as well as through suppression of angiogenesis, primarily by reducing the production of endothelial growth factor. The organ-protective and antiinflammatory potential of drugs that reduce the production of AT, which has been proven in in vitro and in vivo experiments, allows us to consider them as first-line angiotropic agents in patients with rheumatoid arthritis, especially in the presence of concomitant hypertension and/or nephropathy.

YOUNG SCIENTISTS FORUM

760-766 1311
Abstract
During the first months after initiation of urate-lowering therapy in patients with gout, the risk of exacerbating arthritis substantially increases, frequently causing them to refuse this treatment. The main way to avoid this risk is the preventive administration of colchicine, nonsteroidal anti-inflammatory drugs, or glucocorticoids. This prevention of arthritis attacks is stipulated in the latest versions of many national and international guidelines; nevertheless, this tactic is rarely used in practice. The review presents the most significant studies on this problem.

ОБЗОРЫ

767-776 2794
Abstract
Behсet's disease (BD) is a systemic vasculitis of an unknown etiology characterized by repeated oral and genital ulcerations and involvement of the eyes, joints, blood vessels, and other organs. In BD, it is the organ pathology that determines the severity and prognosis of the disease. The most difficult and least studied version of such changes is intestinal damage. Its verification in BD is complicated by a variety of clinical manifestations, their similarity with inflammatory bowel diseases, the lack of sufficiently informative laboratory tests, and pathognomonic endoscopic and histological signs. Intestinal BD (IBD) can result in serious complications (severe bleeding, intestinal perforation, and fistula formation), which may not only considerably reduce the quality of life of the patient, but also cause his death. Treatment for IBD is not standardized; it is mainly empirical and is performed as cycles. The goal of its therapy is to achieve clinical remission, to heal intestinal ulcers, to reduce recurrence rates, and to prevent surgery. The cumulative frequency of surgical interventions is as follows: 20% of them are performed in the first year, 27–33% within 5 years, and 31–46% within 10 years after IBD diagnosis. One of the problems in the surgical treatment of patients with IBD is the risk of a recurrence that often requires repeat surgery. Thus, 2- and 5-year postoperative recurrence rates were 29.2 and 47.2%, respectively. The poor prognostic factors are young age (<40 years), high disease activity at the time of diagnosis, detection of crateriform or deep ulcers at colonoscopy, high C-reactive protein level, and history of laparotomy.
777-781 1782
Abstract

As of now, there are several pharmacological directions in the treatment and prevention of Raynaud’s syndrome and digital ulcers, including various vasoactive drugs (calcium channel blockers, intravenous prostanoids, endothelin receptor antagonists, phosphodiesterase 5 inhibitors, antiplatelets, and statins). The approach to treating systemic sclerosis-related digital ulcers is multifactorial: prevention of risk factors, local and systemic drug treatment, and surgical treatment if necessary.

CLINICAL OBSERVATIONS

782-784 1272
Abstract
Relapsing polychondritis (RP) is a generalized progressive autoimmune inflammatory disease of the cartilaginous tissue, which leads to structural changes in the cartilage until its complete disappearance. To date, about 800 RP cases have been described in the world. The clinical manifestations of RP are diverse, which often complicates the early diagnosis of the disease. The most commonly used drugs to stop RP activity are glucocorticoids, the dose of which depends on the severity of its clinical manifestations, but there is no evidence for their effect on the progression of the process and the risk of relapse. The paper describes a clinical case of early diagnosis and successful treatment of the disease, which could prevent possible complications and disability in the patient.
785-790 1166
Abstract
Toxic epidermal necrolysis (TEN) has been long believed to be the most severe manifestation of drug allergy. However, cutaneous changes as TEN in systemic lupus erythematosus (SLE) were first described in the late 1970s. As of now, the English-language literature published reports of 30 cases of such lesions in SLE. This paper describes a clinical case of TEN as a direct manifestation of SLE; the positive experience has been first depicted in using not only intravenous immunoglobulin, but also rituximab with a good therapeutic effect in Russian clinical practice.

ORTHOPEDIC RHEUMATOLOGY AND REHABILITATION

791-796 1025
Abstract

Surgical treatment in patients with rheumatic diseases (RDs) is associated with the higher risk of complications due to the presence of the inflammatory process, to long-term therapy with glucocorticoids, disease-modifying antirheumatic drugs, and biologic agents (BA), to decreased physical activity, and the severity of functional disorders, and to obvious osteoporosis. All this increases the risk of intraoperative complications, including periprosthetic fractures.
Objective: to comparatively analyze intraoperative periprosthetic fractures of the greater trochanter, acetabulum, and proximal femur during total hip arthroplasty (THA) in patients with RDs.
Subjects and methods. From 1998 till 2017, a total of 1569 THA were performed in patients with RA, including 464 patients with rheumatoid arthritis (RA), 396 with juvenile rheumatoid arthritis (JRA) and systemic lupus erythematosus (SLE), and 709 with osteoarthritis (OA).
Results and discussion. Periprosthetic fractures after THA were diagnosed in a total of 68 (4.33%) patients, including 23 (4.96%) patients with RA, 27 (6.82%) with JRA and SLE, and 18 (2.54%) with OA; 42 (61.8%) patients with periprosthetic fractures underwent osteosynthesis. Statistical analysis of the findings revealed significantly higher rates of complications in patients with RA and JRA with SLE (p < 0.005).
Conclusion. The findings confirm that the risk of periprosthetic fractures is higher in patients with inflammatory diseases, including RA, JRA, and SLE. These patients require a special approach that involves medical correction of impaired bone metabolism and proper individual selection of endoprosthetic components, by taking into account the anatomical features of female patients and delicate bone handling during surgery.

797-804 982
Abstract

Patients who have undergone large (hip, knee) joint replacement constitute a group at high risk for developing venous thromboembolic events (VTEs). According to different authors, the risk of nonpreventable VTEs in these patients varies from 40 to 80%.
Objective: to analyze the incidence of VTE and the risk of postoperative wound-related bleeding and complications in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) after total hip arthroplasty.
Subjects and methods. The investigation enrolled 486 patients with RA (n=212) and OA (n=274) who underwent primary hip arthroplasty. Each patient group was divided into three subgroups according to prevention with the following drugs: 1) nadroparin calcium; 2) dabigatran etexilate; 3) nadroparin calcium switched to dabigatran etexilate. According to the International Society on Thrombosis and Haemostasis criteria, intra- and postoperative blood loss was assessed during the first 7 days after surgery; the wound healing process was also evaluated.
Results and discussion. VTE was prevented with the drugs in 239 (49.2%) patients, 130 (26.8%) of them received nadroparin calcium, the remaining 117 (24.0%) patients had dabigatran etexilate or both drugs. Postoperative VTEs were recorded in 36 (7.4%) out of the 486 patients. VTEs were detected significantly less frequently In RA than in OA (1.2 and 6.1%, respectively; p=0.0013). VTEs were more commonly asymptomatic in both groups. No fatal bleeding was seen in any patient, which confirms the safety of anticoagulant therapy. Blood transfusions were more frequently given to bleeding patients with RA than to those with OA (14.4 and 5.7% of cases, respectively; p<0.001). The number of patients with RA who required discontinuation of anticoagulant therapy was more than those with OA (6.6% and 1.4%, respectively). Delayed wound healing was also much more common in patients with RA (n=56; 26.4%) than in those with OA (n=14; 5.1%). VTE occurred much more often in patients receiving monotherapy with nadroparin calcium than in those having combined therapy (p<0.0001), and somewhat more frequently than in those taking dabigatran etexilate (p=0.054), however, the difference for the latter did not reach statistical significance.
Conclusion. During elective hip replacement, VTEs occurred less frequently in patients with RA than in those with OA (1.23 and 6.17%, respectively, p=0.0013). After hip arthroplasty, VTEs were detected significantly more often in nadroparin calcium-treated patients with RA and OA than in patients receiving combined therapy. Postoperative wound-related bleedings were significantly more frequently observed in RA than in OA (14.4 and 5.7% of cases, respectively). The risk of postoperative wound-related complications in RA is much higher than in OA (relative risk, 4.33; 95% confidence interval, 2.67–7.03; p<0.001), which increases the length of hospital stay and the cost of the treatment performed.

DISCUSSION

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Abstract
The paper discusses the issues of imperfect 1987 American College of Rheumatology (ACR) and the 2010 ACR/European League Against Rheumatology (EULAR) rheumatoid arthritis classification criteria and justifies the need for their correction.


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ISSN 1995-4484 (Print)
ISSN 1995-4492 (Online)