Vol 94, No 5 (2022)

Cover Page

Full Issue


Janus kinase inhibitors in immunoinflammatory rheumatic diseases

Nasonov E.L.


Despite great advances in the diagnosis and treatment of immunoinflammatory rheumatic diseases, which have led to a significant improvement in the prognosis in many patients, the fundamental medical problems of this pathology – the restoration of the quality of life and the reduction of mortality to the population level – are far from being resolved. This served as a stimulus for the study of new approaches to the pharmacotherapy of IVRD, one of which is associated with the use of low molecular weight chemically synthesized drugs that inhibit intracellular "signaling" molecules – Janus kinase. Modern advances regarding the use of Janus kinase inhibitors in the treatment of immunoinflammatory rheumatic diseases and COVID -19 are considered.

Terapevticheskii arkhiv. 2022;94(5):605-609
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Original articles

Evaluation of the association of polymorphisms of the CYP2C8 gene with the efficacy and safety of ketorolac in patients with postoperative pain syndrome

Muradian A.A., Sychev D.A., Blagovestnov D.A., Petrov D.I., Skukin D.S., Epifanova I.P., Sozaeva Z.A., Kachanova A.A., Denisenko N.P., Abdullaev S.P., Grishina E.A.


Aim. To evaluate the possible association of CYP2C8 gene polymorphisms with the clinical efficacy and safety of ketorolac in relation to postoperative pain.

Materials and methods. The study included 107 patients after video laparoscopic cholecystectomy, who received ketorolac (30 mg 2.0 w/m 3 r/d) as postoperative pain relief. All patients were genotyped for CYP2C8. The pain syndrome was assessed using the visual analog scale, the McGill pain questionnaire. The profile of adverse reactions was assessed by the dynamics of red blood counts, as a possible trigger for the development of gastrointestinal bleeding according to the method of global assessment of triggers (Global Trigger Tool – GTT).

Results. According to visual analog scale data: in carriers of the genotype CYP2C8*3 (rs10509681) and CYP2C8*3 (rs11572080) after 12, 24, 36, 48 hours the intensity of pain syndrome is lower than in carriers of the wild type (p<0.05). According to the McGill pain questionnaire, there were no statistically significant differences in pain intensity between the two groups.

Conclusion. In carriers of the genotype CYP2C8*3 (rs10509681) and CYP2C8*3 (rs11572080), the effectiveness of anesthesia with ketorolac is higher than in carriers of the wild type. Carriage of the genotype CYP2C8*3 (rs10509681) and CYP2C8*3 (rs10509681) does not affect the risk of developing adverse reactions after ketorolac anesthesia.

Terapevticheskii arkhiv. 2022;94(5):610-615
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Successful psychopharmacotherapy of anxiety and depressive disorders improve functional limitations in patients with rheumatoid arthritis

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


Aim. To compare changes in functional limitations in patients with rheumatoid arthritis (RA) and comorbid anxiety and depressive disorders (ADD) treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) alone or in combination with biologic DMARDs (bDMARDs) and/or psychopharmacotherapy (PPT), and to determine predictors of HAQ treatment response.

Materials and methods. 128 RA-patients were enrolled, 86% were women with a mean age of 47.4±11.3 (M±SD) years and a median of RA duration – 96 [48; 228] months. Disease activity was assessed using DAS28, functional limitations – using Health Assessment Questionnaire (HAQ). The Minimal Clinical Important Difference in HAQ was considered to be 0.22. ADD were diagnosed by a licensed psychiatrist in 123 (96.1%) of RA-pts in accordance with ICD-10 in semi-structured interview. Severity of depression and anxiety was evaluated with Montgomery–Asberg Depression Rating Scale and Hamilton Anxiety Rating Scale. RA-pts with ADD were divided into the following treatment groups: 1 – сsDMARDs (n=39), 2 – сsDMARDs + PPT (sertraline or mianserine; n=43), 3 – сsDMARDs + bDMARDs (n=32), 4 – сsDMARDs + bDMARDs + PPT (sertraline or mianserine; n=9); 83 (67.5%) patients were assessed at 5-years follow-up. Multivariable logistic regression was performed to determine predictors of HAQ treatment response.

Results. Only remission of anxiety and depressive symptoms at 5-yrs endpoint (OR 6.6, 95% CI 1.78–24.43, p=0.005), higher baseline HAQ (OR 2.61, 95% CI 1.12–6.11, p=0.027) and lower baseline BMI (OR 0.9, 95% CI 0.85–0.96, p=0.001) were independently associated with HAQ treatment response at 5-years follow-up.

Conclusion. While ADD do affect functional limitations in patients with RA, PPT tends to attenuate the negative impact of ADD on RA outcomes, and RA patients with functional limitations should therefore be screened for depression and long-term PPT should be recommended.

Terapevticheskii arkhiv. 2022;94(5):616-621
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The burden of progression of psoriatic arthritis. All-Russian register data

Korsakova Y.L., Loginova E.Y., Korotaeva T.V., Gubar E.E., Glukhova S.I., Vasilenko E.A., Nasonov E.L.


Background. Psoriatic arthritis (PsA) is a complex immune-mediated disease in which a third of patients with psoriasis (PsO) have a inflammatory lesion of both the musculoskeletal system (peripheral joints and axial structures) and extra-articular manifestations (dactylitis, enthesitis, nail PsO, uveitis and inflammatory bowel disease).

Aim. To assess the burden of PsA progression in real practice according to the Russian register of PsA patients.

Materials and methods. Seven hundred thirty seven – M/F=350 (47.5%)/387 (52.5%) – patients with PsA from the Russian register of PsA patients were included. Mean age 47.4±12.7 yrs., duration of PsO 200.6±158.9 mo., PsA – 79.6±81.9 mo. All patients were divided into 2 groups by PsA duration: 1st gr ≤36 mo – 288 (39.1%) and 2nd gr >36 mo – 449 (60.9%). All patients underwent standard clinical examination of PsA activity. Tender (68) and swelling (66) joint count (TJC, SJC), DAPSA, LEI, tenderness of the plantar fascia, PsO BSA (%), PASI, HAQ-DI, PsAID-12, BMI (kg/m2), ESR (mm/h), CRP (mg/l) and comorbidities by ICD-10 were evaluated. Parametric and non-parametric methods of statistical analysis were used. All p<0.05 were considered to indicate statistical significance.

Results. In patients with PsA duration >36 mo we found significant prevalence of erosions by X-Ray, axial PsA, BMI>30 kg/m2, HAQ-DI>1, PsAID-12>4, arterial hypertension, metabolic syndrome and overall comorbidity (p<0.05). There were no significant differences between groups in PsO severity by BSA>3%, PASI>1, LEI>1, TJC, SJC, dactylitis, ESR>30 mm/h, CRP>10 mg/l, DAPSA, diabetes mellitus, hyperlipidemia, coronary heart disease and liver damage (p>0.05).

Сonclusion. Long-standing stage PsA is associated with erosions, axial PsA, worst health related quality of life, functional disability and increased cardio-metabolic disorders and overall comorbidity. Our results support the idea to start bDMARDs at early stage of PsA, it can improve better outcomes.

Terapevticheskii arkhiv. 2022;94(5):622-627
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Antibodies to the phosphatidylserine/prothrombin complex in the diagnosis of antiphospholipid syndrome

Reshetnyak T.M., Cheldieva F.A., Cherkasova M.V., Lila A.M., Nasonov E.L.


Aim. To determine the significance of antibodies to the phosphatidylserine/prothrombin complex (aPS/PT) in patients with systemic lupus erythematosus (SLE) antiphospholipid syndrome (APS).

Materials and methods. A total of 190 patients were included in the study: 123 (64.7%) with reliable SLE and 55 (29%) with PAPS. The control group included 100 relatively healthy subjects of comparable age. All patients were tested for classical aPL as well as IgG/IgM-anti-PS/PT by enzyme immunoassay.

Results. Based on the average values of IgG/IgM aPS/PT of the control group, the levels of positivity were allocated mean (M) + 3 or 5 standard deviations (SD): M+3SD and M+5SD. IgG aPS/PT levels above 73.6 U/ml (M+5SD) were more accurate diagnostic, for IgM aPS/PT – above 18.0 U/ml. IgG-aPS/PT were detected in 84 (44%) of 190 patients. Levels above diagnostic levels were detected in 68 (65%) of 104 patients with APS (55 with PAPS and 59 with SLE+APS). Thrombosis was significantly more common in patients with IgG aPS/PT compared with patients negative for IgG aPS/PT. Arterial but not venous thrombosis was associated with IgG aPS/PT positivity.

Conclusion. The frequency of detection of IgG aPS/PT in the examined patients was 44%, IgM aPS/PT – 29% and their combination – 19% of 190 patients. Half of the patients with probable APS had positive IgG aPS/PT and third – IgM aPS/PT. Median IgG aPS/PT were significantly higher in patients with APS compared to patients without APS and the control group. Thrombosis was associated with IgG aPS/PT. Arterial thrombosis was significantly more frequently reported in patients with IgG aPS/PT. The sensitivity of IgG aPS/PT for reliable APS at levels greater than 73.6 units/ml was 59%, specificity – 92%, for IgM aPS/PT – 35% and 91%, respectively.

Terapevticheskii arkhiv. 2022;94(5):628-634
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Immuno-inflammatory rheumatic diseases and COVID-19: analysis of clinical outcomes according to the data of the register of patients of the Novosibirsk region receiving therapy with genetically engineered biological drugs

Korolev M.A., Letyagina E.A., Sizikov A.E., Bogoderova L.A., Ubshaeva Y.B., Omelchenko V.O., Akimova A.A., Mullagaliev A.A., Chumasova O.A., Kurochkina Y.D.


Background. Currently, observations are accumulating indicating the negative effect of therapy with a number of biologic disease-modifying anti-rheumatic drugs (bDMARDs) drugs on the course of COVID-19. These facts determine the relevance of studying the factors of severe course and unfavorable outcome in immuno-inflammatory rheumatic diseases (IIRD) patients treated with bDMARDs in order to develop tactics for managing this category of patients in a pandemic.

Aim. To evaluate the influence of clinical and demographic factors on the risk of development, severity of the course and clinical outcomes of a new coronavirus infection in patients suffering from IIRD and receiving therapy with genetically engineered biological drugs.

Materials and methods. A retrospective analysis of the database of the register of patients with IIRD receiving bDMARDs in the Novosibirsk region was performed, which included 318 patients, 94 of whom had indications of having suffered viral infection/pneumonia for the period from 01.04.2020 to 31.12.2020.

Results. According to the data obtained, at the time of the analysis, 94 people out of 318 patients with IIRD had a new coronavirus infection. Most (53%) of the patients had a mild infection. At the same time, the nosological form, the use of anti-rheumatic drugs and glucocorticoids did not increase the risks of severe coronavirus infection. When using bDMARDs, only anti-B-cell therapy (rituximab) associated with statistically significant increase in the risk of severe/extremely severe COVID-19. The mortality rate according to the analysis of the register was 6,38%.

Conclusion. Patients with IIRD have a high risk of severe coronavirus infection, while the severity of the disease is associated with the type of therapy performed.

Terapevticheskii arkhiv. 2022;94(5):636-641
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Achievement of clinical-laboratory and ASAS-partial remission in patients with early axial spondyloarthritis according to the ESAC cohort at the 3rd year of follow-up

Timokhina D.G., Dubinina T.V., Demina A.B., Krichevskaya O.A., Erdes S.F.


Background. According to the «treat-to-target strategy» for spondyloarthritis (SpA), the main goal is to achieve clinical remission or inactive disease. In 2001, the Assessment of Spondyloarhtritis International Society (ASAS) formulated the ASAS criteria for partial remission, and the Russian expert group for the study of SpA identified clinical-laboratory remission (no clinical manifestations of the disease that persists for 6 months in the presence of normal values of C-reactive protein and erythrocyte sedimentation rate), magnetic resonance imaging (MRI) remission and complete remission (a combination of clinical-laboratory and MRI remission).

Aim. To determine the frequency of achieving clinical-laboratory and ASAS partial remission in patients with early axial SpA (axSpA) at the 3rd year of follow-up.

Materials and methods. The study included patients from the ESAC cohort (Early SpondyloArthritis Cohort), formed at the Nasonova Research Institute of Rheumatology (Moscow). Currently, the cohort includes 175 patients with axSpA. The analysis included 66 patients followed for at least 3 years, of which 37 (56%) were men and 29 (44%) were women. The average age of the patients was 31.5 (±5.7) years, the average duration of the disease was 22.1 (±17.0) months, 63 (95.4%) patients had HLA-B27 antigen.

Results. Clinical-laboratory remission was achieved by 21 (31.8%) patients with early axSpA at the 3rd year of follow-up, ASAS partial remission – by 29 (44.0%) patients.

Conclusion. In the 3rd year of follow-up of patients with early axSpA, 32% of patients achieved clinical-laboratory remission, and 44% of patients achieved ASAS partial remission. More than 40% of patients with early axial spondyloarthritis achieve remission while taking non-steroidal anti-inflammatory drugs.

Terapevticheskii arkhiv. 2022;94(5):642-646
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Activity of ankylosing spondylitis in women within one year after childbirth

Krichevskaya O.A., Dubinina T.V., Ilinykh E.V., Glukhova S.I., Demina A.B., Andrianova I.A.


Aim. To assess the dynamics of activity of ankylosing spondylitis (AS) during the year after childbirth, to identify predictors of high activity.

Materials and methods. 75 pregnant with confirmed AS (modified New York criteria, 1984) were included for prospective observation. Of these, 44 women were followed up for 1 year after delivery. The average age of the patients was 32.5±5.8 years, the duration of the disease was 149.0±96.3 months. Lactation was established in 40 women and the duration was 10 [4; 12] months.

Results. The BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) at 1, 6 and 12 months after giving birth was 2.4 [1.4; 4.2], 2.6 [1.4; 4.4] and 2.7 [1.5; 4.1], respectively (p>0.05). ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score – C-reactive protein) was 2.0 [1.2; 2.7], 1.9 [1.4; 2.5] and 1.7 [1.3; 2.3], respectively (p>0.05). There were no differences between the values of BASDAI, ASDAS-CRP between women with and without lactation. Predictors of high AS activity (BASDAI≥4) 1 month after delivery were: BASDAI≥4 in the 1st (odds ratio – OR 8.1; 95% confidence interval – CI 1,8–37,0) and 2nd trimesters of pregnancy (OR 5.1, 95% CI 1.2–20.6); NRS back pain >4 in the 2nd trimester (OR 4.3, 95% CI 1.1–17.2); cancellation of biological disease-modifying antirheumatic drugs therapy in the 1st trimester of pregnancy (OR 21.0, 95% CI 1.0–440.9). Predictors of high AS activity in 6 months after delivery were: BASDAI≥4 in the 1st (OR 6.5, 95% CI 1.5–28.7), in the 2nd (OR 6.7, 95% CI 1.6–27.8) and in the 3rd trimesters of pregnancy (OR 8.7, 95% CI 1.9–38.6); high activity in 1 month after delivery (OR 4.0, 95% CI 1.0–15.9).

Conclusion. AS activity remains stable for 1 year after delivery. High AS activity during pregnancy was a risk factor for high activity within 6 months after delivery.

Terapevticheskii arkhiv. 2022;94(5):647-653
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Phenotypes of body composition, physical performance and quality of life in women with rheumatoid arthritis

Dobrovolskaya O.V., Toroptsova N.V., Feklistov A.Y., Demin N.V., Sorokina A.O., Nikitinskaya O.A.


Aim. To evaluate the frequency of different body composition phenotypes, physical performance (PP) and their relationship with quality of life in women with rheumatoid arthritis (RA).

Materials and methods. The study included 157 women (average age 58.6±8.8 years) with RA. Clinical and laboratory examination, dual-energy X-ray absorptiometry, quality of life assessment according to the questionnaires EQ-5D (European Quality of Life Questionnaire), HADS (Hospital Anxiety and Depression Scale) and RAID (Rheumatoid Arthritis Impact of Disease), determination of muscle strength and the PP of skeletal muscles were carried out.

Results. Osteoporotic, sarcopenic and osteosarcopenic phenotypes of body composition were identified in 27 (17%), 16 (10%) and 16 (10%) patients, respectively; 139 (88.5%) people had low muscle strength, and 96 (61.1%) had reduced PP. Quality of life according to the EQ-5D index and RAID, the severity of depression according to HADS in women with different phenotypes of body composition did not differ. Women with osteosarcopenic phenotype had worse indicators for EQ-5D-VAS (VAS – visual analog scale), and patients with sarcopenic phenotype had more severe anxiety according to the HADS questionnaire compared to those with normal phenotype (p=0.014 and p=0.027, respectively). The quality of life according to all questionnaires was significantly worse in patients with reduced PP.

Conclusion. Pathological phenotypes of body composition were found in 37% of RA patients. A decrease in muscle strength was revealed in 88.5%, and a low PP – in 61.1% of patients. The relationship between quality of life and body composition has not been established, at the same time quality of life associated with the PP of skeletal muscles.

Terapevticheskii arkhiv. 2022;94(5):654-660
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Difficult-to-treat rheumatoid arthritis in real clinical practice. Preliminary results

Galushko E.A., Gordeev A.V., Matyanova E.V., Olyunin Y.A., Nasonov E.L.


Aim. To compare the features of the course of the disease and the therapy in rheumatoid arthritis (RA) patients who meet the criteria of difficult-to-treat RA (D2T).

Materials and methods. The study included 505 RA patients (ACR/EULAR 2010). Rheumatologist experts discussed all patients, since the treatment of RA ware perceived as problematic and/or insufficient. All patients had at least one of the following signs: the activity of the disease is no lower than moderate; the inability to reduce the dose of glucocorticoids to low; rapid radiological progression; RA symptoms causing a decrease in quality of life. The D2T group included 35 patients with true inefficiency or intolerance of two or more of bDMARDs/tsDMARDs of different mechanism of action. The control group (K) included patients with RA who already had experience of taking at least one class of bDMARDs/tsDMARDs (n=291).

Results. On average, every 15 patients (7%) with RA met the EULAR criteria for D2T. The median age of patients in the D2T group was 45 years, which is less than in K (Me 54 [43; 62] years; p=0.046). The duration of RA in both groups was comparable. The severity of articular destruction in D2T was higher than in K (stage IV in 40% and 23%, respectively). Positivity for the RF and ACPA in D2T was less common than in K (60% and 85.9%; 60% and 76.6%, respectively). The presence of systemic manifestations of RA was more typical for K than for D2T (28.6% and 63%, p=0.0001). In the group of D2T patients, the number of previously taken DMARDs was higher than in K (p=0.002). Methotrexate was more often prescribed as the first DMARDs in both groups (in 62.9 and 65.7%, respectively). Initiation of bDMARDs/tsDMARDs therapy in D2T was more often performed by TNF-a inhibitors (OR 2.8; p=0.003) and co-stimulation blocker – abatacept (OR 4.6; p=0.004), and in control – by B-cell inhibitor rituximab (OR 6.9; p<0.0001).

Conclusion. The results of this study suggest that in Russia, as well as abroad, the principle of RA treatment “treat to target” has not yet become widespread, and the development of adequate therapy takes too much time.

Terapevticheskii arkhiv. 2022;94(5):661-666
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Levilimab and baricitinib prescribing experience in outpatient COVID-19 patients’ treatment

Khripun A.I., Starshinin A.V., Antipova Y.O., Lysenko M.A., Urozhaeva Y.V., Gavrilenko O.F., Rusantsova N.A., Tyazhelnikov A.A., Tikhonovskaya E.Y., Okolot N.V., Sokolova M.V., Fomina D.S., Simonova E.N., Kruglova T.S., Chernov A.A., Zagrebneva A.I.


Aim. To study the effect of levilimab or baricitinib in combination with standard therapy (ST) on the incidence of severe viral pneumonia associated with a new coronavirus infection COVID-19.

Materials and methods. A multicenter, open-label observational study of the efficacy and safety of levilimab in combination with ST (group 1, n=100), baricitinib in combination with ST (group 2, n=139), or in comparison with ST (group 3, n=200) in outpatients with verified CT-1 pneumonia.

Results. According to the results of laboratory tests, patients treated with levilimab in combination with ST had the best dynamics of changes in CRP from reliably the highest level (mg/L) to the lowest in comparison with other groups. In the group of patients with ST, in contrast to the other groups, no dynamics of CRP was observed by day 5 of therapy. In group of hospitalized patients initially receiving levilimab in addition to ST, the rate of transfer to the intensive care unit (2 patients, 9.52%) and length of stay (4 days) was significantly lower compared to the values in patients in both the baricitinib group in combination with ST (7 patients, 15.56%; 5 days [interquartile range 3–6.5]) and in patients receiving ST alone (7 patients, 15.56%; 5 days [interquartile range 3–6.5]). Also in hospitalized patients we observed no statistically significant intergroup differences in the incidence of infectious complications and thromboembolic events, which confirms the safety of including levilimab or baricitinib in COVID-19 pathogenetic therapy regimens. Observational results support the hypothesis that the initial inclusion of levilimab or baricitinib in addition to ST is accompanied by a reduced risk of viral pneumonia progression.

Conclusion. The addition of levilimab or baricitinib to the therapy regimen for coronavirus infection during the outpatient phase has demonstrated a preemptive anti-inflammatory effect and reduced the probability of lung tissue damage progression.

Terapevticheskii arkhiv. 2022;94(5):668-674
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Efficacy and safety of regdanvimab in patients with mild/moderate COVID-19 and high risk of progression of the disease: a retrospective study in a short-term stay unit

Markina U.A., Fomina D.S., Lebedkina M.S., Kruglova T.S., Chernov A.A., Zagrebneva A.I., Mutovina Z.Y., Karaulov A.V., Alexeeva E.I., Lysenko M.A.


Background. The use of virus-neutralizing monoclonal antibodies is an effective method of etiotropic therapy for SARS-CoV-2 in patients of high-risk groups of severe COVID-19. Regdanvimab is a single-component monoclonal antibodies immunoglobulin G1, whose mechanism of action is aimed at binding SARS-CoV-2 virus at the RBD site of the spike protein S1 domain. In the Russian Federation, regdanvimab is approved for emergency administration in COVID-19 for adult patients not requiring respiratory therapy who are at high risk of developing a severe course of the disease.

Aim. To evaluate the efficacy and safety of therapy with regdanvimab in patients with mild/moderate COVID-19 in a short-term hospital unit.

Materials and methods. Virus-neutralizing therapy with regdanvimab was performed at the short-term hospital unit of the Moscow City Clinic. An open retrospective observational single-center study included 92 adult patients with mild/moderate coronavirus infection. All patients had comorbid chronic diseases and belonged to the high-risk group for the development of a severe COVID-19. Inclusion criteria: age 18 to 75 years; presence of a verified diagnosis of COVID-19 of mild/moderate COVID-19, polymerase chain reaction (PCR) confirmed; one or more chronic diseases; first 7 days from the onset of the first symptoms of COVID-19 (including day 7). Exclusion criteria: need for oxygen support. Clinical efficacy was assessed according to the World Health Organization Сlinical Progression Scale and supplemented with laboratory markers at baseline and in dynamics, as well as with monitoring of virus elimination by PCR.

Statistics. Calculations were performed using the statistical computing environment R 4.1.3 (R Foundation for Statistical Computing, Austria). For quantitative indices the median (1; 3 quartiles) was indicated. For binomial signs we calculated 95% confidence intervals according to Wilson's method. Time interval analysis was performed according to the Kaplan–Meier method. The significance level was determined at p<0.05.

Results. A significant decrease in the severity of clinical manifestations according to the World Health Organization Clinical Progression Scale was noted by patients by day 4 after regdanvimab administration. All 92 patients in the cohort were discharged from the hospital l on average on day 5 after regdanvimab administration and on day 9 of the disease. On day 4 after drug administration 82% of patients was being PCR negative. No adverse events related to the administration of regdanvimab were reported during the study.

Conclusion. In real clinical practice, the efficacy and safety of regdanvimab in patients at high risk of severe COVID-19 was confirmed once again, with a positive clinical result observed in a mixed cohort by the causative agent omicron and delta strain.

Terapevticheskii arkhiv. 2022;94(5):675-682
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Endogenous estrogen deficiency and the development of chronic musculoskeletal pain: A review

Panevin T.S., Bobkova A.O., Karateev A.E., Zotkin E.G.


Sexual dimorphism of chronic diseases is a phenomenon determined by differences in the hormonal status of men and women. In this regard, estrogens, which have a complex effect on the body, are of great interest. In particular, estrogens play an important role in the natural control of pain and inflammation. A decrease in estrogen levels associated with menopause or iatrogenic effects (hysterectomy, use of aromotase inhibitors), as well as mutations of genes responsible for the synthesis of structural components of membrane estrogen receptors (ESR1 and ESR2), can significantly reduce the positive effects of these hormones. Deficiency of estrogen can become one of the reasons for the development of serious pathological changes – in particular, the formation of chronic pain associated with the pathology of the musculoskeletal system.

Terapevticheskii arkhiv. 2022;94(5):683-688
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On the specific treatment of asthenic states: focus on sulbutiamine

Bykov Y.V., Bekker R.A.


In this article, we try to present the available data regarding the pharmacokinetics and pharmacodynamics of sulbutiamine (Enerion®), the mechanisms of its anti-asthenic action. Then we analyze and summarize the available evidence base considering the efficacy and safety of Enerion® for the treatment of asthenic syndromes. Then we compare Enerion® with some other drugs. The results of our review indicate the high efficacy and safety of sulbutiamine in the treatment of asthenia. Our results also show that Enerion® has some clinically relevant advantages over all alternatives we reviewed there.

Terapevticheskii arkhiv. 2022;94(5):689-694
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Non-infectious diseases of the aorta and large arteries

Beketova T.V.


This article describes the various forms of inflammatory lesions of the aorta and large arteries, including chronic periaortitis, as well as the diagnostic methods are considered. Large vessel vasculitis represent the most common entities, however, there is also an association with other rheumatological or inflammatory diseases, drug-induced or paraneoplastic entities. Instrumental imaging modalities play an important role in the diagnosis.

Terapevticheskii arkhiv. 2022;94(5):695-703
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History of medicine

Classification of systemic vasculitis: evolution from eponyms to modern criteria

Bulanov N.M., Novikov P.I., Litvinova M.A., Moiseev S.V.


Systemic vasculitis is a manifold group of systemic autoimmune diseases characterized by the inflammation of the blood vessels. The first clinical cases of systemic vasculitis were described in the Middle Ages, and most of the currently recognised nosological forms were reported in the first half of the 20th century. The first attempt to create a united classification of vasculitis was performed by P. Zeek in 1952. In the following decades accumulation of the data on the etiology and pathogenesis of different vasculitis guided researchers from different countries in their attempts to improve classification. The main principles of classification were the size of the affected blood vessels, disease etiology and pathogenesis. In 1990 American College of Rheumatology (ACR) published classification criteria for seven forms of the systemic vasculitis, that gave a significant contribution to the conduction of large-scale studies in this field. However, the first international nomenclature of vasculitis was developed only in 1994 during the Consensus Conference in Chapel Hill. Revised and augmented version of this nomenclature was created in 2012 and is still valid. An important step in the development of the classification of vasculitis was a joint project of ACR and EULAR aimed to develop new diagnostic and classification criteria for vasculitis (DCVAS). The first result of this project are the new classification criteria for granulomatosis with polyangiitis, microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis published in 2022. In general, the evolution of the classification of vasculitis occurs under the influence of the progress in the understanding of their etiology and pathogenesis.

Terapevticheskii arkhiv. 2022;94(5):704-708
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