Vol 91, No 5 (2019)


Rheumatoid arthritis: achievements and unresolved issues

Nasonov E.L., Lila A.M.


Success in a treatment of rheumatoid arthritis (RA), associated with a development of new medications and improving treatment strategies, allows to achieve remission in many patients. Despite this a lot of theoretical and clinical issues remain, including a definition of the term "remission", its characteristics and types as well as approaches to optimal tactics of "symptomatic" and "pathogenetic" drug therapy at different stages of the disease. Use of a such tactics will allow to induce quickly a state of remission and maintain it for a long term. Further research is needed which should be directed to investigation of a heterogeneity of RA pathogenetic mechanisms and to elaboration of approaches to its early diagnosis as well as to improving methods for monitoring a disease activity, biomarkers of efficacy and resistance to therapy, and finally, to developing of a differentiated therapy, including a search for new “therapeutic” targets.
Terapevticheskii arkhiv. 2019;91(5):4-7
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Chronic pain and depression in patients with rheumatoid arthritis: results of five - year follow - up

Lisitsyna T.A., Abramkin A.A., Veltishchev D.Y., Seravina O.F., Kovalevskaya O.B., Zeltyn A.E., Glukhova S.I., Nasonov E.L., Krasnov V.N.


The aim of the study was to analyze the factors affecting chronic pain in patients with rheumatoid arthritis (RA). Materials and methods. 128 patients with reliable diagnosis of RA [111 (86.7%) women and 17 (13.3%) men] were examined. The mean age of patients was 47.4±11.3 years, the median duration of the disease was 96 [48; 228] months. When included in the study in most patients, the activity of RA in DAS28 was moderate (n=56; 43.7%) or high (n=48; 37.5%). BPI (Brief Pain Inventory) scale was used to determine the severity of pain and its impact on various aspects of life. The anxiety - depressive spectrum disorders (ADDs) were diagnosed by psychiatrist during a semistructured interview according to ICD-10 criteria in 123 (96.1%) patients. The severity of depression was determined by the Montgomery-Asberg depression rating scale, anxiety - by Hamilton anxiety scale. For the diagnosis of cognitive impairment used clinical and psychological techniques. Psychopharmacotherapy (PPhT) by antidepressants or anxiolytics is offered to all patients with ADDs, 52 of them agreed to treatment, 71 patients refused. The next groups selected depending on the therapy: 1st - with conventional disease - modifying antirheumatic drugs (cDMARDs; n=39), 2nd - with cDMARDs+PPhT (n=43), 3d - with cDMARDs + biologic (b) DMARDs (n=32), 4th - with cDMARD+bDMARDs+PPhT (n=9). The dynamics of ADDs and outcomes of RA in 5 years were evaluated in 83 (67.5%) patients. Results. When included in the study, 94 (75.2%) patients with RA had moderate and severe pain. According to the regression analysis, the maximum intensity pain in BPImax after 5 years of follow - up associated not the only factors connected with RA - high DAS28, the serum level of C-reactive protein, the degree of radiological stage and functional insufficiency, duration of RA and a lesser duration of glucocorticoids intake, but also with continuing depressive episodes in the framework of recurrent depression and the initial presence of cognitive impairment. The severity of pain after 5 years of follow - up was higher in RA patients receiving only сDMARDs, without the use of bDMARDs and in the absence of PPhT associated with ADDs. Conclusion. Depressive episode within recurrent major depression is a significant factor in the chronicity of pain in patients with RA. Timely effective PPhT of depression, selected taking into account depression structure and personal characteristics of the patient, leads to a steady decrease in the severity of pain in patients with RA.
Terapevticheskii arkhiv. 2019;91(5):8-18
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Effectiveness and safety of selective and non - selective factor Xa inhibitors in antiphospholipid syndrome and systemic lupus erythematosus: anti - Xa - activity range

Seredavkina N.V., Reshetnyak T.M., Satybaldyeva M.A., Kashnikova L.N., Temnikova T.A., Nasonov E.L.


The aim of the study was to evaluate the anti - Xa - activity (aXa) of selective and non - selective factor Xa inhibitors in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) patients according to clinical implications and laboratory parameters. Materials and methods. Clinical and laboratory data were analyzed retrospectively in SLE and APS patients who protractedly received low weight molecular heparins (LWMH) and selective factor Xa inhibitors fondaparinux and rivaroxaban. The study included 70 patients in the middle age 39 [31; 43] years: 15/70 (21%) - with SLE, 10/70 (14%) - with APS and 45/70 (65%) - with SLE and APS (SLE+APS). All the patients received anticoagulants: 29 patients - nadroparin (98.3 [67.8; 129.5] IU/kg/day), 29 patients - fondaparinux (5 [5; 7.5] mg/day), 3 patients - enoxaparin (1.2 [0.8; 1.5] mg/day) and 9 patients - rivaroxaban (20 mg/day). All the patients signed informed consents. Results. aXa therapeutic range of 0.1-1.5 IU/ml was found in 43/70 (61%) patients, low aXa - in 14/70 (20%) and high aXa - in 13/70 (19%) patients. Patients with low aXa underwent anticoagulant dose correction. There were not any major bleedings and thrombosis relapses in the study. Increased aXa was more common in patients, who took fondaparinux (31%), than in those, who took nadroparin (7%) and rivaroxaban (23%), p=0.02. Patients with enoxaparin had normal aXa range. In the absence of bleeding in SLE and APS patients, received anticoagulants in standardized therapeutic dose, the next factors influenced the aXa range excess: valvular heart disease (VHD) with the 3rd stage of mitral valve insufficiency as a result of aseptic Libman-Sacks endocarditis (odds ratio - OR 9.02, 95% confidential interval - CI [1.53; 53.12], p=0.015), peripheral artery disease in analogy with arteritis obliterans (AO) (OR 6.86, 95% CI [1.25; 37.71], p=0.027), and also triple - positivity of all types of antiphospholipid antibodies (OR 4.93, 95% CI [1.11; 21.99], p=0.036). According to found logistic regression model, aXa range excess risk can be prognosticated by the next formula: Z = -3.98 + 2.2 × VHD (yes-1/no-0) + 1.9 × AO (yes-1/no-0) + 1.6 × Triple - positivity (yes-1/no-0). Classified function value Z=0.39 defines the patients group with aXa range excess. Thus the value Z>0.39 indicates aXa range excess in the absence of bleeding, herewith sensibility is of 77% and specificity is 86%, positive prognostic value is 84.3%. Conclusion. In SLE and APS patients the next clinical and immunologic manifestations influenced the aXa therapeutic range excess: peripheral artery disease in analogy with AO, earlier aseptic Libman-Sacks endocarditis with the 3rd stage of mitral valve insufficiency and triple - positivity of all types of antiphospholipid antibodies, that does not need LWMH and fondaparinux dose correction. In contrast, anticoagulant dose reduction can cause clinical symptoms progression. Therapeutic aXa range in such patients should be extended.
Terapevticheskii arkhiv. 2019;91(5):19-25
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The role of laboratory biomarkers in monitoring of rituximab biosimilar therapy (Acellbia, “BIOCAD”) in patients with rheumatoid arthritis

Avdeeva A.S., Cherkasova M.V., Kusevich D.A., Rybakova V.V., Artyuhov A.S., Dashinimaev E.B., Chichasova N.V., Nasonov E.L.


Aim: to evaluate the role of laboratory biomarkers in monitoring effectiveness of rituximab (RTM) biosimilar therapy in a total dose of 1200 mg. Materials and methods. 20 patients (pts) with rheumatoid arthritis (RA) (18 woman, mean age 61.5(54-66.5) years, mean disease duration 39.5(20-84) months, mean DAS28 5.6(4.9-6.8)) received two intravenous RTM biosimilar infusions (600 mg №2) in combination with DMARDs and glucocorticoids. Laboratory biomarkers were assessed at baseline and weeks 12 and 24 after the first infusion of RTX. Results. RTM biosimilar induced decreases in DAS28, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) at week 12 and 24, p<0.05. The decrease in the concentration of immunoglobulin (Ig) M rheumatoid factor (RF) was detected at week 12 and 24 and amounted to 79.7% and 87.1% of the initial level, respectively (p<0.05). IgA RF level decreased by 72% and 85% from baseline, respectively, at the 12 and 24 week of RTM therapy in patients with a good effect of the drug (p<0.05). The concentration of antibodies to cyclic citrullinated peptide in the sera did not reduced. Depletion of CD19+ B-cells was achieved at week 12 in all patients (absolute number 0), with an increase in the level of B-cells at week 24 (0.0030 (0.0003-0.0270) 109/l). The immunoglobulin level decreased at week 24, but remained normal. RTM biosimilar therapy was accompanied by a rapid and pronounced decrease in the concentration of cytokine profile by 12-24 weeks after the first infusion. Conclusion. RTX biosimilar therapy induced a rapid and significant improvement in ESR, CRP, IgM/IgA RF, anti-MCV, proinflammatory cytokines, chemokines and growth factors levels and CD19+ B-cells depletion in RA pts. IgM RF and/or antibodies to citrullinated proteins seropositivity, increased levels of interleukin-17 after 12 weeks of treatment can be considered as predictors of a good response to RTM biosimilar therapy.
Terapevticheskii arkhiv. 2019;91(5):26-33
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Level of N-terminal fragment of brain natriuretic peptide progenitor and atherosclerotic damage of brachocephalic arteries in patients with rheumatoid arthritis with inefficiency and/or injurability of basic anti - inflammatory treatment

Gerasimova E.V., Popkova T.V., Martynova A.V., Markelova E.I., Novikova D.S., Kirillova I.G.


The high prognostic significance of the concentration of the N-terminal - pro-B-type natriuretic peptide (NT-proBNP) in the development of cardiovascular diseases (CVD) was identified for rheumatoid arthritis (RA) and general populations. Aim: to investigate the significance of NT-proBNP level in patients (pts) with RA with the ineffectiveness and/or intolerance of basic anti - inflammatory therapy; compare the level of NT-proBNP with atherosclerotic lesion of the brachiocephalic arteries (BCA), traditional risk factors and inflammatory markers. Materials and methods. The investigation enrolled 28 pts (24women/4men) with the lack of efficacy/resistance and/or intolerance of basic anti - inflammatory drugs (DMARDs); median age was 55 [46; 61] years, median disease duration 114 [60; 168] month; DAS28 6,2 [5.1; 7.0]; SDAI 35.0[23.9; 51.0], CDAI 30.0[21.0; 42.0], serum positivity for rheumatoid factor (RF) (100%)/anti - cyclic citrullinated peptide antibodies (ACCP) (86%). The study did not include RA pts with congestive heart failure. High incidence of traditional risk factors was found in RA pts: arterial hypertension - in 75%, dyslipidemia - 61%, smoking - 17%, overweight - 61%, family history of cardiovascular diseases - 36%, hypodynamia - 68%. Coronary artery disease was diagnosed in 11% RA pts. Lack of efficacy of 3 or more DMARDs was found in 46% of pts, intolerance to previous therapy with DMARDs - in 54% pts. 47% were receiving methotrexate (20 [18; 25] mg/week), 11% - leflunomide, 7% - sulfasalazine, 46% - glucocorticoids, 75% - non - steroidal anti - inflammatory drugs. The control group consisted of 20 healthy donors, comparable to pts by age and sex. Serum levels of of NT-proBNP were measured using electrochemiluminescence method Elecsys proBNP II (Roche Diagnostics, Switzerland). The determination of the intima - media thickness (IMT) BCA were assessed from duplex scanning. Atherosclerotic lesion of BCA was assessed by the presence of atherosclerotic plaque (IMT ≥1.2 mm). Results. NT-proBNP concentrations in RA pts proved to be higher (78.7 [41.4; 101.3] pg/ml) than those in the control group (55.3 [36.6; 67.3] pg/ml, p<0.05). RA pts were divided into two groups according to the level of NT-proBNP: >100 pg/ml - 1 group (n=6) and ≤100 pg/ml - 2 group (n=22). Groups of RA pts did not differ in gender, age, activity of RA, frequency of detection of traditional risk factors. Atherosclerotic lesion of the BCA was detected in 3 (50%) pts of the 1 group and in 8 (36%) pts of the 2 group (p>0.05). In RA pts the level of NT-proBNP correlated with age (r=0.39; p<0.05), with the IMT BCA (r=0.43; p<0.05). In RA pts of the 2 group, a correlation was observed between the concentration of NT-proBNP and the level of ACCP (r=0.42; p<0.05) and antibodies to modified citrullinated vimentin (anti-MCV; r=0.56; p<0.05). No association of NT-proBNP with PA activity (DAS28, CDAI, CDAI), inflammatory markers (C-reactive protein, erythrocyte sedimentation rate), traditional risk factors and therapy was found. Conclusion. The level of NT-proBNP in the blood of RA pts with ineffectiveness and/or intolerance to basic anti - inflammatory therapy is higher than in the control group. In every fifth RA patient, the concentration of NT-proBNP was higher than 100 pg/ml. The association of NT-proBNP with age and immunological parameters (ACCP and anti-MCV) was demonstrated. The correlation between the concentration of NT-proBNP and the IMT BCA may indicate the possible role of this biomarker in the progression of atherosclerotic lesions of arteries in RA pts. The significance of NT-proBNP in the development of early manifestations of atherosclerosis in RA requires further study.
Terapevticheskii arkhiv. 2019;91(5):34-39
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Clinical and laboratory characteristics of IgG4-realated disease and its diagnostic algorithm

Sokol E.V., Vasilyev V.I., Palshina S.G., Kokosadze N.V., Probatova N.A., Kovrigina A.M., Safonova T.N., Rodionova E.B., Gaiduk I.V., Selifanova E.I.


Aim: to propose diagnostic algorithm of IgG4-related disease (IgG4-RD). Materials and methods. One center retrospective research. 52 pts with IgG4-RD were included. The diagnosis was proved histologically and immunohistochemically. 48 out of 52 pts received treatment. Treatment included one of the following schemes (along with low oral glucocorticoids): rituximab monotherapy, cyclophosphamide monotherapy or their combination. Results. The mean age was 47.4±5.9 years, the mean age of the disease onset was 43.9±16.0 years. Median time before the diagnosis was 24 months. The most often sites of IgG4-RD were lacrimal (63.5%), salivary (46.2%) glands, lungs (48%), lymph nodes (34.6%) and retroperitoneum (17.3%). In clinical picture the leading complain was organ enlargement, but not its dysfunction. Pain was characteristic for retroperitoneum localization. In 56.8% of pts with IgG4-related syalo - and/or dacryoadenitis there was association with ear - nose - throat organs affection. In 4 pts (7.7%) IgG4-RD was combined with some malignant disease, including MALT-lymphoma of lacrimal glands. Irreversible organ damage as an IgG4-RD outcome had 15.4% of pts. The main laboratory markers of IgG4-RD were ESR elevation (38.5%), blood eosinophilia (9.6%), immunological disturbances (serum total IgG and IgG4 elevation, IgE elevation, antinuclear antibodies, rheumatoid factor detection, hypocomplementemia). Serum IgG4 level >1.35 g/l was elevated in 88% of pts and correlated with the number of affected organs (Spearman correlation coefficient 0.39, Student’s test, р=0.0056). Monoclonal serum secretion and B-cell clonality in the tissue was detected in 4 (23.5%) out of 17 pts, but not all of them had both signs. Conclusion. Based on the analysis of clinical and laboratory characteristics of IgG4-RD a diagnostic algorithm was proposed that enhances the detection and examination of the patients with suspected IgG4-RD.
Terapevticheskii arkhiv. 2019;91(5):40-48
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Idiopatic Lobular Panniculitis as a common clinical problem

Egorova O.N., Belov B.S., Glukhova S.I., Radenska-Lopovok S.G.


Aim. To present clinical and laboratory characteristics of various forms of idiopatic lobular panniculitis (ILP) in modern rheumatology practice. Materials and methods. The study included 67 people (58 women and 9 men aged 20 to 76) with the referral diagnosis of "Erythema nodosa? Undifferentiated panniculitis?" in 76.2% of cases with a median disease duration of 78.91 [48; 540] months observed in the V.A. Nasonova Research Institute of Rheumatology. In 2007-2017 in addition to general clinical examination immunological, histological and immunohistochemical studies, computed tomography (CT) of the chest organs and tuberculin tests were performed. Results. Analysis of clinical manifestations allowed to distinguish four forms of ILP: nodular (n=30), plaque (n=10), infiltrative (n=15) and mesentric (n=12). The minimum median duration of the disease was detected in plaque form (8 [5; 11.5] months), while the median duration in case of infitrative form was 8.25 times longer (66 [36; 102] months, p<0.001). As a result of the meta - analysis, the typical prognostic factors for various ILP forms were identified: nodular - multiple symmetrical nodes; plaque - fever >38 °C and a small number (up to 5) of drain nodes; infiltrative - fever >38 °C, ulceration of nodes with the expiration of oily mass and scarring; mesenteric - pain in the abdominal area, the number of nodes less than 5 and the abdominal cavity CT results (inflammation of the adiopose tissue of the intestinal mesentery, omentum, adipose tissue of the pre - and retroperitoneal areas). Conclusion. The forms and activity of the disease determine the approaches to treatment in modern clinical practice. There is an obvious need to expand knowledge about this pathology among doctors and conduct further research in order to timely diagnose and search for the most effective methods of ILP treatment.
Terapevticheskii arkhiv. 2019;91(5):49-53
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Sjögren's syndrome with juvenile onset

Kaleda M.I., Nikishina I.P., Latypova A.N.


Aim to analyze demographic data, clinical features and results of laboratory and instrumental examinations in children with primary and secondary Sjögren syndrome (SS). Materials and methods. The study included all consequently patients, who hospitalized to the pediatric department of V.A. Nasonova Scientific and Research Institute of Rheumatology from January 2013 to December 2018, which verified the diagnosis of the SS. Results. The diagnosis of SS was established in 30 patients, among whom there were only 5 (16.7%) boys, the ratio of boys and girls was 1:5. According to the results of the examination, the following diagnoses were verified: 4 - primary SS, 9 - systemic lupus erythematosus with SS, 10 - juvenile rheumatoid arthritis with SS, 3 - mixed connective tissue disease, 3 - overlap syndrome, 1 - systemic sclerosis with SS. The median age of rheumatic disease onset was 10.4 (7.0; 13.75) years. The median of disease duration at the time of SS verification - 3.0 (0.85; 4.4) years. Recurrent parotitis were observed in 8 patients. 24 pts had isolated involvement of salivary glands, 6 - combined with lacrimal glands. Sicca syndrome was occurred in 8 patients. All patients had systemic manifestations: constitutional abnormalities - 50%, polyarthritis - 83.3%, lymphadenopathy - 73.3%, cutaneous involvement - 60%, pulmonary involvement - 23.3%. Of the hematological disorders, leuko/lymphopenia was more often recorded - in 30%, polyclonal hypergammaglobulinemia - in 26.7% of patients. ANA were detected in all cases, anti-Ro antibodies - 60%, a positive rheumatoid factor - 56.7% of patients. The most common combination of immunological disorders was the presence of ANA, RF and anti-Ro antibodies (40% of patients). The treatment for each patient was justified by the main manifestations and activity of rheumatic disease: 66.7% received nonsteroidal anti - inflammatory drugs, 80% - glucocorticoids, 46.7% - methotrexate, 20% - azathioprine, 43.3% - hydroxychloroquine, 10% - mycophenolatis mofetilum, 3.4% - cyclophosphamide. 66.7% of patients received the treatment of Biologics. Conclusions. Early diagnosis of SS in children with rheumatic diseases significantly affects to the choice of treatment and prognosis. In children the SS has no clinical manifestations for a long time. Such symptoms as a hypergammaglobulinemia, positive RF without persistant arthritis, nonspecific skin lesions, recurrent parotid swelling may help to diagnosis of SS.
Terapevticheskii arkhiv. 2019;91(5):54-60
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The сhanges of bone mineral density on the risk of progression of osteoarthritis of the knee

Kashevarova N.G., Taskina E.A., Alekseeva L.I., Demin N.V., Lila A.M., Nasonov E.L.


Aim. To find the relationship between bone mineral density (BMD) and risk of knee OA progression in a 5-year prospective study. Materials and methods. 110 females with knee OA were examined twice with 5-year interval. Examination included filling questionnaires, VAS pain assessment, plain knee radiography and axial skeleton densitometry. I stage knee OA was established in 33 (30%) patients, II stage - in 46 (41.8%), III stage - in 26 (23.6%), and IV - in 5 (4.5%). Normal lumbar vertebrae densitometry BMD values were found in 45 patients (40.9%), osteopenia - corresponding BMD values - in 33 (30.0%), and osteoporosis - in 32 (29.1%). Normal femoral neck BMD values were identified in 60 (54.5%) patients, osteopenia - level BMD - in 48 (43.7%), osteoporosis - in 2 (1.8%). In all premenopausal patients (n=15) axial skeleton BMD values were normal. Results. In 5-year interval radiographic progression was established in 40 patients (Group 2), while in 70 (Group 1) patients no progression occurred. Both groups were comparable in terms of age and disease duration, although, more patients from Group 2 tended to have normal baseline densitometry BMD values - both in lumbar vertebrae and femoral neck: 47.5% vs 37.1%, and 62.5% vs 44.3% as compared to Group 1 patients. Patients from Group 1 more often had BMD values corresponding to osteoporosis and osteopenia: 32.9% vs 22.5%, and 55.7% vs 37.5%, respectively, as compared to Group 2 patients, although not achieving statistical significance. These differences were still identifiable after 5-year interval. Absolute BMD values at the second examination in 5 years were indicative of statistically significant increase in femoral neck and total hip BMD in Group 2 patients with knee OA progression: 0.79±0.11 vs 0.73±0.16, р<0.01, and 0.93±0.14 vs 0.84±0.25, р<0.05, respectively. Thorough analysis of lumbar vertebrae BMD (g/cm2) relationship with OA stages revealed that in patients with stage IV OA lumbar BMD values were significantly higher than in patients with stages I-III OA (stage I OA - BMD 0.87±0.12 g/cm2; stage II OA - 0.92±0.21 g/cm2; stage III OA - 0.88±0.13 g/cm2, stage IV OA - BMD 1.07±0.17 g/cm2). Femoral BMD values didn’t show evident correlation with knee OA stage, although there was a trend towards higher BMD values in patients with stage IV OA compared to stage III OA (р=0.06). Total hip BMD values were quite similar to lumbar BMD values (р=0.01). BMD values were statistically significantly higher in patients with stage IV OA, than in patients with stages I and III (respectively, IV - 0.98±0.13 g/cm2, I - 0.85±0.10 g/cm2 and III - 0.86±0.16 g/cm2). Correlation analysis also confirmed direct correlation between knee OA stage and BMD values in all evaluated compartments (p<0.05). Conclusion. Increasing during the 5-eyar follow up period femoral neck and total hip BMD values can be interpreted as the predictor of knee PA progression. More advanced OA stages are associated with higher BMD values.
Terapevticheskii arkhiv. 2019;91(5):61-67
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What factors affect the effectiveness of long - term analgesic therapy for osteoarthritis? Data analysis of the multi - center 3-month PARACELSUS study

Karateev A.E., Lila A.M., Pogozheva E.Y., Amirdzhanova V.N., Filatova E.S.


There are factors that can affect the effectiveness of treatment of osteoarthritis (OA). Aim to identify factors affecting the effectiveness of long - term analgesic therapy in OA. Materials and methods. The study included 6448 patients (70.9% female and 29.1% male), middle age 57.8±10.2 years, with severe pain [≥40 mm on the visual analog scale]. All patients received the preparation of avocado - soybean unsaponifiables (ASU) 300 mg/day. For pain relief at the beginning and during the study, the drug Ketoprofen lysine salt (KLS) 320 mg/day was used. The efficiency criterion was pain reduction ≥50% and satisfaction with treatment ≥4 on a 5-point scale. The influence of a number of factors on the result of treatment was evaluated. Results. For 3 months of treatment, the pain decreased from 63.7±12.0 to 14.2±11.7 mm VAS. The result was evaluated as "good" or "excellent" 81.7% of patients. Adverse reactions were rare. In total, a good response to therapy was noted in 87.4% of patients. Gender, body mass index ≥30 kg/m2, type 2 diabetes mellitus, poor effect of non - steroidal anti - inflammatory drugs (NSAIDs) and Symptomatic Slow-Acting Drugs in Osteoarthritis (SYSADOA) in history did not affect the result. The effect was lower in persons >65 years [odds ratio (OR) 0.418; 95% confidence interval (CI) 0.342-0.509, p<0.001], with radiological stage >2 by Kellgren-Lawrence (OR 0.556; 95% CI 0.298-0.738, p<0.001), with pain at rest (OR 0.690; 95% CI 0.596-0.800, p<0.001), synovitis (OR 0.778; 95% CI 0.673-0.900, p=0.001), pain in the enthesis region (OR 0.846; 95% CI 0.616-0.957, p=0.032), and also in the presence of central sensitization descriptors (CS; OR 0.530; 95% CI 0.458-0.613, p<0.001). Conclusion. The combination of ASU and NSAID (KLS) allows for successful control of pain in OA. Factors such as age >65 years, stage OA of K/L >2, pain at rest, synovitis, pain in the region of enthesis and the presence of CS descriptors associated with the worst treatment outcome.
Terapevticheskii arkhiv. 2019;91(5):68-75
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Pulmonary hemorrhage in rheumatic diseases

Kraeva V.V., Beketova T.V.


In the article, we report the causes of pulmonary hemorrhage (PH) according to the literature data and own experience, with an emphasis on patients suffering from rheumatic diseases. Methods of diagnosis and modern approaches to the treatment of PH are analyzed.
Terapevticheskii arkhiv. 2019;91(5):76-83
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Spondyloarthritis: modern terminology and definitions

Erdes S.F., Rebrov A.P., Dubinina T.V., Badokin V.V., Bochkova A.G., Bugrova O.V., Gaydukova I.Z., Godzenko A.A., Dubikov A.A., Ivanova O.N., Korotaeva T.V., Lapshina S.A., Nesmeyanova O.B., Nikishina I.P., Otteva E.N., Raskina T.A., Rumyantseva O.A., Sitalo A.V., Smirnov A.V.


Aim to identify outdated terms and make changes to the terminology of spondyloarthritis. Materials and methods. At the first stage of the work, the terms divided into two categories: “outdated” definitions and terms that need to be improved or unified. Subsequently, each member of the Expert Group of Spondyloarthritis at the Association of Rheumatologists of Russia (ExSpA) presented by its own definition of the designated term or agreed with the previous term. At the next stage, the existing definitions were put together. After discussion, experts left a term that scored at least 2/3 of the votes. The special opinion of experts was recorded, whose did not coincide with the majority opinion. An open vote was conducted, when defining an “outdated” term with the unanimous decision of all group members, this term was not recommended for further clinical use. Results. The work carried out allowed us to identify a number of terms that are not recommended for use in clinical practice. Number of terms are defined, which should be used when discussing the problem of spondyloarthritis. Conclusion. The Expert Group of Spondyloarthritis at the Association of Rheumatologists of Russia suggests using or, accordingly, not using a number of terms and their definitions in clinical practice.
Terapevticheskii arkhiv. 2019;91(5):84-88
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Endothelial damage and circadian blood pressure profile in rheumatoid arthritis

Shilkina N.P., Yunonin I.E., Butusova S.V., Mikhailova E.V., Vinogradov A.A.


Aim. To study the influence of the state of endothelium on the daily profile of arterial pressure (AP) in patients with rheumatoid arthritis (RA). Materials and methods. In 70 RA pts carried out C-reactive protein (CRP), vascular endothelial adhesion molecule type 1 (sVCAM-1), antigen von Willebrand Factor (AG WF), interleukin-8 (Il-8), rheumatoid factor (RF), IgG, endotheline-1 (ET-1), number of desquamated endotheliocytes cells (DE), VS, activity of renin by immunoenzyme analysis. The dysfunction of endothelium was evaluated by calculation of DE. The functional methods included the daily monitoring of arterial pressure (AP). Results. Arterial hypertension (AH) occurred in 40 (57.1%) pts. RA pts are revealed the signs of endothelial dysfunction, about which significant differences among the indices of activation of endothelium in comparison with control group testify. ET-1, sVCAM-1, vWF AG, Il-8, CRP content was higher in RA pts. Reliably above there was a number of DE. Reliable differences according to these indices depending of RA activity were discovered. With conducting of correlation analysis it is revealed, that markers of the activation of endothelium: sVCAM-1, vWF AG positively correlated with increasing RF IgG and indices of the immune inflammation: CRP, and DE number. In patients suffering from RA, showed signs of endothelial dysfunction. The positive correlation between endothelial damage and daily profile of AP show the relationship of these processes. Conclusion. Positive correlations between the damage of endothelium and disturbance of AP daily profile testify about the interrelation of these processes.
Terapevticheskii arkhiv. 2019;91(5):89-95
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The effectiveness of complex therapy using the injectable form of chondroitin sulfate and sodium hyaluronate with osteoarthritis of the knee joint

Belyaeva E.A., Avdeeva O.S.


Aim. The study on the effectiveness of complex therapy for osteoarthritis (OA) of the knee joint was conducted in real clinical practice. Materials and methods. The survey involved 125 patients aged fr om 50 to 70 years (25 men and 100 women) with a diagnosis of knee joint OA (the III roentgenologic Kellgren-Lawrence stage).The average age of the patients was 62±3.21, the average duration of the disease - 9.4±2.8 years. Patients were randomly assigned to three groups of 35 people, the control group had 20 patients. Group 1 patients received non - steroidal anti - inflammatory drugs (NSAIDs) + Injectran(Chondroitin sulfate) 200 mg intramuscularly (I.M.) every other day No. 25.In group 2, patients received NSAIDs + Fermatron 1% 2 ml with an interval of 7 days intra - articularly (I.A.) No. 3. In group 3 - NSAIDs + Injectran 200 mg (I.M.) every other day No. 25 + Fermatron 1% 2 ml with an interval of 7 days (I.A.) No. 3. In the control group (20 people), patients received only NSAIDs. Evaluation of the symptoms was carried out using the WOMAC index before the start of thetherapy, after 8 and 12 weeks of treatment. The intensity of pain while walking was estimated on a visual analogue scale. Results. In the groups that received Injectran (I; group 1) or Fermatron (F; group 2), the dynamics of pain while walking reduction was comparable and had slightly more than 30% in both groups, the figures are reliable in comparison withinitial data (p<0.01). In group 3, wh ere both Injectran + Fermatron (I+F) were used, the pain while movingdecreased by more than 50% in comparison with initial data, i.e. combined use of two medications at the same time allowed to improve the results of treatment by 1.5 times.Patients' need for NSAIDs before and after therapy was also investigated. In all the groups, patients were able to reduce the dose of NSAIDs.In the control group, 80% of patients had the same dose of NSAIDs by the end of the 8th week, whereas in group 3 (I+F) - only 5.7%, in group 2 (F) - 17.1%, in group 1 (I) - 11.5%. Intergroup differences are valid (p<0.001). The number of patients who completely withdraw NSAIDs was the largest in group 3 (I+F; 22.8%), which is 2 times more than in group 2 (F; 11.4%) and 4 times more than in group 1 (I; 5.7%), the differences are valid (p<0.01). Conclusion. By the end of the therapy, the decline in the WOMAC index was mostly in group 3 (I+F) - more than 50%, in the 1st (I) and 2nd (F) groups - more than 40%, in the control group - 20%. After 12 weeks in all the groups there was a tendency to maintain and even increase the effect of the therapy.
Terapevticheskii arkhiv. 2019;91(5):96-102
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Vitamin D - prognostic marker of the risk of exacerbation in patients older than 60 years with osteoarthritis of the knee (results of the observation program DIANA)

Zolotovskaya I.A., Davydkin I.L.


Aim to study the prognostic significance of vitamin D as a marker of the risk of exacerbation of osteoarthritis (OA) of the knee in patients over 60 years. Materials and methods. The study was conducted from 2016-2018 on the of Samara polyclinics with the inclusion of patients who have applied to a doctor for any reason and have a history of OA of the knee joint with the time of the last exacerbation of no more than 6 months. We evaluated clinical and demographic parameters, information on the drugs taken (drugs), the nature of pain by DN4, the level of cognitive deficiency by MMSE, office blood pressure data, left ventricular ejection fraction, determined the level of hemoglobin, glucose, uric acid, interleukin (IL) 1β and IL-6, 25(OH)-D. the Duration of follow - up was 36 months. Results. During 2 years of follow - up, 79 (38.3%) patients had exacerbation, which occurred in 19.4% (n=40) of cases during the first year, and in 18.9% (n=39) of cases respectively during the second year. In 35.4% of cases, the neuropathic component of pain was noted with an index of 4.37±1.05 points. Age, 25-OH-vitamin D, IL-1β, and the presence of diabetes mellitus and chronic kidney disease are factors that affect the prognosis of exacerbation in patients with OA of the knee joint. Conclusion. The prognostic significance of vitamin D for the risk of exacerbation in patients with OA older than 60 years (χ2=160.9, р<0.001).
Terapevticheskii arkhiv. 2019;91(5):103-110
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Intestinal manifestations of Behçet's disease

Goloeva R.G., Alekberova Z.S., Lisitsyna T.A., Stepanova E.A., Orlova L.P.


Behçet's disease (BD) is a systemic vasculitis of unknown origin, characterized by recurrences of the ulcerative process in the oral cavity and on the genitals, inflammatory damage of the eyes, joints, vessels and other organs. The severity and prognosis of BD determines organ pathology. Intestinal manifestations of BD (intestinal BD) are the least studied. Its verification in BD is complicated by the variety of clinical manifestations, their similarity with inflammatory bowel diseases, the lack of informative laboratory tests, pathognomonic endoscopic and histological signs. Intestinal BD can lead to serious complications (massive bleeding, intestinal perforation and fistula formation), which can not only significantly reduce the quality of the patient’s life, but also cause death. Treatment of intestinal BD is not standardized; it is mainly empirical and conducted courses. The purpose of therapy is to achieve clinical remission, healing of intestinal ulcers and prevention of surgery. The article presents a case of severe refractory intestinal BD, requiring twice emergency surgical care - removal of half and then the whole of the colon because of multiple perforations. A brief review of the literature is given and diagnostic difficulties of intestinal BD are discussed.
Terapevticheskii arkhiv. 2019;91(5):111-119
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Comorbidity in gout and hyperuricemia: prevalence, causes, prospects of urate lowering therapy

Eliseev M.S., Novikova A.M.


Nowadays, there is increased interest in the connection of gout and asymptomatic hyperuricemia with comorbid conditions such as diabetes mellitus, cardiovascular diseases, hypertension, chronic kidney disease and other. Studies conducted over the past few decades suggest that not only gout, but also asymptomatic hyperuricemia can significantly worsen the prognosis in patients with cardiovascular diseases, as the deposition of urate crystals can be both an immediate cause and a factor in the progression of renal failure. In that way, the timely appointment of urate - lowering therapy and achieving the target serum uric acid level can not only affect joint damage, but also can significantly slow the progression of life - threatening comorbid conditions.
Terapevticheskii arkhiv. 2019;91(5):120-128
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Chronic kidney disease in rheumatoid arthritis patients: prevalence, risks factors, histopathological variants

Chebotareva N.V., Guliaev S.V., Androsova T.V., Milivanova L.U.


The present review is focused on risk factors of chronic kidney disease in rheumatoid arthritis (RA). According to recent data, the chronic kidney disease (CKD) in RA patients is more often than at patients without RA. It is closely associated with risk of cardiovascular disease and high mortality. Besides of general population risk factors of CKD, the activity of the disease is independent predictors of reduction in glomerular filtration rate less than 60 ml/min/1.73 m2. In the review, histopathological variants and mechanisms of CKD on basis of international experience are also considered. Suppression of inflammation by basic therapy of RA and biological therapy have changed outcomes RA, prevalence, and structure of kidney involvement in recent years.
Terapevticheskii arkhiv. 2019;91(5):129-133
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Alflutop - in modern symptom - modifying osteoarthritis therapy

Drozdov V.N., Shikh E.V., Serebrova S.Y., Abrosimov A.G., Starodubtsev A.K.


One of the serious problems during the treatment of osteoarthritis (OA) is the developing of adverse drug events during therapy. Nonsteroidal anti - inflammatory drugs (NSAIDs) are the first drugs with the high incidence and severity of adverse events. This article describes OA treatment strategies approaches for OA are presented using the complex drug Alflutop, which has a composition similar to the human hyaline cartilage. The drug has anti - inflammatory and analgesic effects, normalizes the function of the affected joints, improves the quality of patients’ life, also has a structure - modifying effect. Such therapy is safe, well tolerable for patients, and can be used used as a starting complex OA treatment.
Terapevticheskii arkhiv. 2019;91(5):134-140
pages 134-140 views

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