Vol 93, No 5 (2021)

Cover Page

Full Issue


2019 Coronavirus disease (COVID-19): contribution of rheumatology

Nasonov E.L.


The 2019 coronavirus disease (COVID-19) pandemic become a major challenge for humanity and a unique opportunity to get an idea of the real achievements of modern biology and medicine. In the course of the pandemic, a large number of new fundamental and medical issues have been revealed regarding the relationship between viral infection and many common chronic non-infectious diseases, among which immune-mediated rheumatic diseases (IMRD) occupy an important position. It is now well known that SARS-CoV-2 infection is accompanied by a wide range of extrapulmonary clinical and laboratory disorders, some of which are characteristic of IMRD and other autoimmune and autoinflammatory diseases in humans. The most severe consequence of alterations in regulation of the immunity in COVID-19 and IMRD is the so-called cytokine storm syndrome, which is defined as COVID-19-associated hyperinflammatory syndrome in COVID-19, and as macrophage activation syndrome in IMRD. The COVID-19-associated hyperinflammatory syndrome was used as a reason for drug repurposing and off-label use of a wide range of anti-inflammatory drugs, which have been specially developed for the treatment of IMRD over the past 20 years. Common immunopathological mechanisms and approaches to pharmacotherapy in COVID-19 and IMRD determined the unique place of rheumatology among medical specialties contributing to combat the COVID-19 pandemic. The article provides the basic provisions of the International and National Association of Rheumatologists and the Association of Rheumatologists of Russia (ARR) recommendations for management of patients with IMRD during the COVID-19 pandemic.

Terapevticheskii arkhiv. 2021;93(5):537–550
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Original articles

Influence of successful psychopharmacotherapy of anxiety-depressive spectrum disorders on the severity of chronic fatigue 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 assess the influence of psychopharmacotherapy (PPT) of anxiety and depressive disorders on fatigue severity in patients with rheumatoid arthritis (RA).

Materials and methods. 128 RA-patients were included. Severity of fatigue was measured with fatigue severity scale (FSS), clinically important fatigue was diagnosed in patients with FSS≥4. Anxiety and depressive disorders (ADD) were diagnosed by a licensed psychiatrist in 123 (96.1%) of RA-patients in accordance with ICD-10 in semi-structured interview. Severity of depression and anxiety was evaluated with Montgomery–Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A). RA-patients with ADD were divided into the following treatment groups: 1 – сDMARDs (n=39), 2 – сDMARDs+PPT (sertraline or mianserine), n=43, 3 – сDMARDs+bDMARDs (n=32), 4 – сDMARDs+bDMARDs+PPT (sertraline or mianserine), n=9. Biologics treatment duration varied from 1 to 5 years, antidepressants – from 6 to 96 weeks. 83 (67.5%) RA patients were assessed at five-years follow-up. Multinominal logistic regression analysis was conducted to determine factors associated with clinically important fatigue.

Results. Multinominal logistic regression analysis showed clinically important fatigue at baseline to be positively associated (OR 13.57; 95% CI 3.044–60.486; p=0.01) and remission of ADD – negatively associated (OR 0.162; 95% CI 0.032–0.809; p=0.027), with clinically important fatigue at 5 years follow-up (R2=0.385, p<0.0001).

Conclusion. Due to significant relationship between mental health status, antidepressants treatment and clinically important fatigue in RA-patients, all patients reporting clinically important fatigue should be recommended mental health counselling by a licensed psychiatrist.

Terapevticheskii arkhiv. 2021;93(5):551–560
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Application of cardiovascular risk scales to identify carotid atherosclerosis in patients with rheumatoid arthritis

Gerasimova E.V., Popkova T.V., Gerasimova D.A., Glukhova S.I., Nasonov E.L., Lila A.M.


Aim. To evaluate the cardiovascular risk (CVR) and analyze its relationship with detection of early carotid artery atherosclerotic lesion in patients with rheumatoid arthritis (RA).

Materials and methods. One hundred and nine RA patients aged 45 to 60 without established cardiovascular diseases (CVD) were included in the study. The median age was 52 [48; 54] years, duration of RA was 120 [36; 204] months, DAS28 was 4.7 [3.5; 5.6] points. CVD risk was calculated with mSCORE, Reynolds Risk Score (RRS), ASSIGN, QRISK3, ERS-RA scales and Carotid Artery Doppler Ultrasound Exam was performed for all patients.

Results. High risk was found in 5, 5, 14, 6, and 38% of patients according to mSCORE, RRS, ASSIGN, QRISK3, ERS-RA scales, respectively. Atherosclerotic plaques of carotid arteries were found in 30% of patients. It was found that carotid intima-media thickness is correlated to all CVR calculators, age, systolic and diastolic blood pressure, cholesterol, erythrocyte sedimentation rate, interleukin-6 levels. The sensitivity and specificity of the CVR algorithms in prognostication of atherosclerotic carotid artery lesions were 73 and 67% for mSCORE, 64 and 63% for RRS, 64 and 56% for ASSIGN, 73 and 49% for QRISK3, respectively, p<0.05 in all cases, 67 and 50% for ERS-RA, p=0.06.

Conclusion. RRS, mSCORE, ASSIGN, QRISK3 calculators equally predict atherosclerotic carotid artery damage in RA patients. The optimal ratio of specificity and sensitivity is shown for the mSCORE scale. Stratification of CVR in RA patients should include assessment of the carotid intima-media thickness. To identify CVR in RA patients, the most informative methods are mSCORE calculation and carotid intima-media thickness determination.

Terapevticheskii arkhiv. 2021;93(5):561-567
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The prevalence of sarcopenia in patients with rheumatological pathology

Lavrishcheva I.V., Jakovenko A.A., Rumyantsev A.S.


Aim. To assess the prevalence of sarcopenia in rheumatological patients.

Materials and methods. 317 patients with rheumatological pathology were examined, among them 201 women and 116 men, the age of patients ranged from 21 to 58 years, the average age at the time of inclusion of patients in the study was 41.1±7.3 years. Sarcopenia was diagnosed using the method recommended by The European Working Group on Sarcopenia in Older People 2.

Results. The frequency of occurrence of a decrease in the appendicular skeletal muscle mass to the appendicular skeletal muscle mass index was 31.2% (99 patients), a decrease in muscle strength according to the wrist dynamometry was observed in 44.5% (141) patients, low skeletal muscle performance according to the results NIH Toolbox 4 Meter Walk Gait Speed Test in 42.8% (135) patients. The prevalence of suspected sarcopenia (probable sarcopenia) was 13.3% (42 patients) and sarcopenia, including severe 31.2% (99) patients. Statistically significant differences were obtained between groups of patients depending on the duration of rheumatological disease and the prevalence of sarcopenia (χ2=19.328; p=0.001).

Conclusion. Sarcopenia occurs in a third of hospitalized rheumatological patients.

Terapevticheskii arkhiv. 2021;93(5):568–572
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The relationship between obesity, cardiometabolic disorders and disease activity in psoriatic arthritis patients: data from the Russian register

Korsakova Y.L., Korotaeva T.V., Loginova E.I., Gubar E.E., Vasilenko E.A., Vasilenko A.A., Kuznetsova N.A., Patrikeeva I.M., Nasonov E.L.


Aim. To study the relationship between obesity, cardiometabolic disorders and disease activity in patients with psoriatic arthritis (PsA) in real practice.

Materials and methods. The Russian register included 614 PsA patients [female – 331 (54%)/283 (46%)]. Average age – 45.2±0.52 years, PsA duration – 5.7±0.27 years, psoriasis – 15.71±0.56 years. Patients underwent examination, body mass index (BMI), PsA activity according to DAPSA, cDAPSA, analysis of concomitant diseases were assessed. The patients were divided into 3 groups depending on BMI (kg/m2): normal <25 (group 1), increased – 25–30 (group 2), obesity >30 (group 3).

Results. The average BMI was 27.7±0.23 kg/m2, normal BMI – in 213 (34.7%), increased – in 214 (34.8%) and obesity – in 187 (30.5%). Concomitant diseases – in 297 (48%). In group 3, arterial hypertension was observed significantly more often than in groups 1 and 2 (p<0.0001); more often than in group 2 – diabetes mellitus (p<0.0001), metabolic syndrome (p<0.0001); more often than in group 1 – ischemic heart disease (p=0.026). PsA activity at Baseline, after 6/12 months was significantly higher in group 3 (p<0.031). In obese patients, the chance of a decrease in disease activity to a moderate/low level and remission during therapy for 6/12 months is 2.484 times lower than in group 1, and 2.346 times lower than in group 2: odds ratio 2.346 (95% сonfidence interval 1.07–5.143) and 2.484 (95% сonfidence interval 1.135–5.439), respectively.

Conclusion. In the majority (65.3%) of PsA patients, BMI exceeded the norm. Obesity is associated with a high incidence of cardiometabolic disorders, with higher PsA activity and lower treatment efficacy.

Terapevticheskii arkhiv. 2021;93(5):573–580
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Vitamin D status in women with rheumatoid arthritis: frequency of hypovitaminosis, associations with disease activity, body composition and comorbidity

Dobrovolskaya O.V., Toroptsova N.V., Nikitinskaya O.A., Samarkina E.Y., Cherkasova M.V., Feklistov A.Y.


Aim. To evaluate the status of vitamin D in women with rheumatoid arthritis (RA) and establish its associations with comorbidity, disease activity, and body composition components.

Materials and methods. 86 women with RA (average age 58.1±8.5 years) were enrolled in the study. We analyzed the relationship of vitamin D levels with clinical and laboratory parameters and with the results of two-energy x-ray absorptiometry. Mann–Whitney or Kruskal–Wallis, χ2 and Spearman tests were performed using Statistica for Windows 10.0 (StatSoft Inc., USA).

Results. Vitamin D level was 22.4 [17.8; 27.3] ng/ml: deficiency was detected in 33%, and insufficiency – in 46% of women with RA. Only 41% of patients with low vitamin D levels received supplements of cholecalciferol, while only 9% – in a sufficient dose. 25(OH)D level was significantly lower in RA patients with sarcopenia, obesity, high activity according to DAS28 and in those who did not receive vitamin D supplements. There weren’t differences in 25(OH)D levels among subgroups of patient according to age, fertility, BMD status, comorbidity index, RA duration, ESR and CRP levels, medical therapy performed.

Conclusion. 79% of patients with RA had low levels of vitamin D, while less than half of them received additional cholecalciferol supplements. Low vitamin D levels in RA patients were associated with high disease activity, sarcopenia, and obesity.

Terapevticheskii arkhiv. 2021;93(5):581-586
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Efficacy of combined use of glycosaminoglycan peptide complex for intramuscular administration and oral diacerein in osteoarthritis: evaluation according to an observational multicenter clinical trial

Karateev A.E., Alekseeva L.I., Pogozheva E.Y., Amirdzhanova V.N., Filatova E.S., Nesterenko V.A., Lila A.M.


Background. The combined use of intramuscular injection glycosaminoglycan peptide complex (GPC) and oral diacerein can increase the effectiveness of treatment of osteoarthritis (OA).

Aim. Compare the effectiveness of combination GPC + diacerein and GPC monotherapy in the treatment of OA in clinical practice.

Materials and methods. A retrospective evaluation of the results of a 12-week multicenter observational non-interventional study of the effectiveness of GPC (Rumalon®, a course of intramuscular injections 3 times a week, №25) in patients with moderate/severe OA (n=2955) requiring regular administration of nonsteroidal anti-inflammatory drugs (NSAIDs). The analysis identified a group of patients (n=414) who received GPC in combination with diacerein 100 mg/day (Diaflex Rompharm). The therapeutic effect was compared in the groups of GPC monotherapy (n=2541) and the combination of GPC with diacerein. These groups did not differ in average age (61.4±11.8 and 61.9±11.3 years), both were dominated by women (76.3 and 70.3%), there was approximately equal intensity of pain during movement and impaired joint function: 6.1±1.8/6.0±1.6 and 4.9±2.1/5.1±1.8 (according to the numerical rating scale 0–10). The dynamics of pain intensity, the need for NSAIDs, and the frequency of adverse events (AE) were compared 12 weeks after the start of treatment.

Results and discussion. In the majority of patients with OA – both on the background of GPC monotherapy and combined use of GPC and diacerein, there was a significant improvement. The number of patients with pain reduction ≥50% was 54.3 and 62.8% (p<0.001), NSAID administration was completely stopped in 66.7 and 77.5% (p<0.001), respectively. The effectiveness of the combination of GPC and diacerein was significantly higher than that of GPC monotherapy in OA of the knee joint, hip joint, and generalized OA. AE from the gastrointestinal tract was observed in 7.8 and 8.9%, arterial hypertension – in 6.3 and 4.6%, allergic reactions – in 0.3 and 0.5% of patients (not significant).

Conclusion. The application of the code of civil procedure is an effective treatment for OA. The combination of GPC and diacerein provides a more significant improvement than GPC monotherapy. GPC and diacerein (including in combination) are well tolerated and rarely cause AE.

Terapevticheskii arkhiv. 2021;93(5):587–593
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Soluble transferrin receptors and ferritin index in the diagnosis of iron deficiency in patients with spondyloarthritis and anemia

Safarova K.N., Dorogoykina K.D., Fedotov E.A., Rebrov A.P.


Aim. To assess the diagnostic value of the detection of soluble transferrin receptors (sTfR) and ferritin index (sTfR/log Fer) in patients with spondyloarthritis (SpA) and anemia for the revealing absolute iron deficiency (ID).

Materials and methods. The study included 68 patients with SpA: median age – 39 [34; 47] years, men: 38 (55.9%). Hemogram, C-reactive protein levels and ferrokinetics parameters were assessed, including sTfR testing by the method of quantitative enzyme-linked immunosorbent assay (Monobind Inc., USA). We also calculated sTfR/log Fer. Based on ferrokinetics parameters and C-reactive protein levels, chronic disease anemia (CDA), iron deficiency anemia (IDA), or their combination (CDA/IDA) were diagnosed.

Results. CDA was diagnosed in 16 patients, CDA/IDA – in 32 patients, and 20 patients had no anemia. An increase in sTfR concentration in patients with CDA/IDA (1.7 [1.4; 2.2] mg/L) compared with patients with CDA (1.5 [1.1; 1.7] mg/L, p<0.05) was revealed. sTfR/log Fer in patients with CDA/IDA (0.93 [0.82; 1.24]) was higher than in patients with CDA (0.64 [0.48; 0.75], p<0.0001). When evaluating the ROC curves, it was found that sTfR levels >1.39 mg/L and sTfR/log Fer levels >0.83 indicate the presence of absolute ID. The area under the ROC curve for sTfR was 0.72 (95% confidence interval 0.60–0.82, p<0.001), for sTfR/log Fer – 0.85 (95% confidence interval 0.74–0.92, p<0.001). The sensitivity and specificity of sTfR/log Fer (75 and 83%, respectively) were higher compared with sTfR (53 and 81%, respectively).

Conclusion. In patients with SpA having CDA/IDA, sTfR and sTfR/log Fer are statistically significantly increased. The results obtained indicate the possibility of diagnosing ID by using these parameters.

Terapevticheskii arkhiv. 2021;93(5):594–598
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Evaluation of topical therapy of patients with osteoarthritis of small joints of the hands with Voltaren® Emulgel® 2% (diclofenac diethylamine 2%)

Tsurko V.V., Gromova M.A.


Aim. To evaluate the efficacy and safety of using the drug Voltaren® Emulgel® 2% (diclofenac diethylaminе 2%) for 14 days in patients with osteoarthritis (OA) of small joints of the hands.

Materials and methods. 62 patients of both sexes with hands OA were included in the study, 31 of whom (main group) used Voltaren® Emulgel® 2% (diclofenac diethylaminе 2%) topically, and the remaining 31 (comparison group) – Voltaren® Emulgel® 2% (diclofenac diethylamine 2%) + oral nonsteroidal anti-inflammatory drugs. The effectiveness of therapy was assessed by using a visual analogue scale (VAS) in dynamics: joint pain and stiffness at rest, pain on movement and during palpation, by functional indices AUSCAN, FIHOA, by assessment of the effect of therapy by the doctor and the patient on a weekly basis.

Results and discussion. Joint pain decreased after 2 weeks of therapy in all patients during treatment with Voltaren® Emulgel® 2% (diclofenac diethylamine 2%) in both groups. Significant reduction in stiffness and improvement in hand joint function was achieved after 7 days and lasted until the end of treatment. By the end of treatment, 100% of patients assessed their condition as improvement.

Conclusion. Voltaren® Emulgel® 2% (diclofenac diethylamine 2%) demonstrates comparable clinical efficacy in patients with OA of the hand joints (reduced pain, stiffness and improved joint function) in monotherapy as complex therapy in combination with oral NSAIDS, while being well tolerated.

Terapevticheskii arkhiv. 2021;93(5):599–604
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Clinical notes

Difficulties in the diagnosis and treatment of comorbid infections with rheumatoid arthritis. Case report

Ryabkova N.L., Marusenko I.M., Ryabkov V.A.


The article presents the case of the diagnosis of sepsis as a variant of a comorbid infection in a patient with cross syndrome (systemic lupus erythematosus and rheumatoid arthritis) on the background of the debut of coronary heart disease (acute myocardial infarction complicated by external rupture of the heart).

Terapevticheskii arkhiv. 2021;93(5):605–608
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New coronavirus infection COVID-19 as a trigger for the development of symptoms of ankylosing spondylitis. Case report

Rumiantceva D.G., Urumova M.M., Erdes S.F.


The novel coronavirus infection COVID-19 (SARS-CoV-2) is now known to cause a variety of extrapulmonary complications, including cardiovascular, neurological and dermatological complications, many of which occur or last several weeks after infection. We present a clinical case of a patient who first developed symptoms of ankylosing spondylitis 2 weeks after recovering from COVID-19. The patient was prescribed therapy in accordance with international and Russian recommendations for the management of patients with ankylosing spondylitis with a positive effect in the form of absence arthritis, enthesitis and reducing the inflammatory back pain.

Terapevticheskii arkhiv. 2021;93(5):609–612
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Locomotive syndrome: from paradigms to clinical reality

Putilina M.V., Teplova N.V., Lila A.M., Zagorodniy N.V.


Locomotive syndrome is an unsatisfactory condition of patients over 60 years of age who need or may require outside help in the near future due to functional deterioration of the musculoskeletal system, including pathology of bone tissue, joints, muscles and nervous tissue. In real clinical practice, one often has to deal with the following manifestations of locomotive syndrome: osteoarthritis, sarcopenia, balance disorders, chronic musculoskeletal pain. Today, there is a clear understanding that drug therapy should be long-term, include comprehensive support for muscle tissue, balance training, and mandatory cognitive-behavioral therapy. Maximum safety of long-term drug therapy can be ensured by the use of vital micronutrients, which include highly purified forms of chondroitin sulfate and glucosamine sulfate, which have a wide range of anti-inflammatory and regenerative effects.

Terapevticheskii arkhiv. 2021;93(5):613–621
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Modern approaches to immunization of patients of rheumatologic profile

Belov B.S., Tarasova G.M., Muravyeva N.V.


Recently, the importance of comorbid infections in rheumatology has increased significantly, which have a significant impact on morbidity and mortality, especially in immuno-inflammatory rheumatic diseases (IIRD). In this regard, vaccination is becoming increasingly important in the prevention of infections in these patients. This review presents an updated version of the recommendations for vaccination of adult patients with IIRD, prepared by experts of the European Union League against Rheumatism (EULAR). There is a low (suboptimal) vaccination coverage of these patients, partly due to the low frequency of referral by doctors. The role of the rheumatology team in solving the problems associated with immunization of patients with IIRD is emphasized, as well as the importance of joint decision-making taking into account the needs and preferences of patients. The issues concerning the use of vaccines against influenza, pneumococcal infection, hepatitis B,

Terapevticheskii arkhiv. 2021;93(5):622–627
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Advantages of the use of metformin in patients with impaired uric acid metabolism

Eliseev M.S., Panevin T.S., Zhelyabina O.V., Nasonov E.L.


Metformin is one of the oldest and at the same time relevant and effective drugs for the treatment of type 2 diabetes. At the same time, the mechanism of the hypoglycemic effect was not completely clear until recently. Current data suggest that the mechanism of action of metformin contributes to the development of an anti-inflammatory effect, as well as a decrease in the level of uric acid, and its use can be potentially useful in patients with hyperuricemia and gout.

Terapevticheskii arkhiv. 2021;93(5):628–634
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The role of the angiotensins in the pathogenesis of inflammatory joint disease

Gordeev A.V., Galushko E.A., Savushkina N.M.


The significant humoral effect of the renin-angiotensin-aldosterone system on the regulation of the cardiovascular system and blood pressure has long been widely known. However, the identification and interpretation of new components of renin-angiotensin-aldosterone system in recent years can significantly expand the range of its potential effects on the body. The anti-inflammatory effect of drugs that block angiotensin II and its receptors, including in rheumatic diseases, can become practically significant for General therapists by their effect on reducing the concentration of inflammatory mediators and angiogenesis processes. The organoprotective and anti-inflammatory potentials of drugs that reduce the production of at demonstrated in vitro and in vivo experiments allow us to consider them as first-line angiotropic agents in patients with rheumatoid arthritis, especially in the presence of pathology of the cardiovascular system and kidneys.

Terapevticheskii arkhiv. 2021;93(5):635-639
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History of medicine

Consent. Modern interpretation: "Voluntary Informed Consent"

Chuchalin A.G.


The article is devoted to voluntary informed consent. It considers the historical issues of the formation of this concept in modern health care and medical science. The article highlights a historical role of the Nuremberg Code which was taken as the basis for the Universal Declaration of Human Rights, the World Medical Association (WMA) Code of Ethics, the Declaration on Bioethics and Human Rights, i.e. documents that defined the world order after the end of World War II.

Terapevticheskii arkhiv. 2021;93(5):640-644
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