Vol 95, No 5 (2023)

Cover Page

Full Issue

Editorial

Systemic lupus erythematosus and antiphospholipid syndrome: past, present, future

Nasonov E.L., Reshetnyak T.M., Solovyev S.K., Popkova T.V.

Abstract

Immune-inflammatory (autoimmune and autoinflammatory) rheumatic diseases are widespread severe chronic inflammatory diseases and also “models” for studying the fundamental mechanisms of pathogenesis and approach to pharmacotherapy of other diseases associated with autoimmunity and/or autoinflammation. Uncontrolled inflammation leading to hypercoagulation forms the basis of “thromboinflammation”, which is considered a universal pathogenetic mechanism of organ involvement in immune-inflammatory rheumatic diseases, as well as in COVID-19 and atherosclerotic vascular lesions (atherothrombosis). Thrombo-inflammatory mechanisms play a crucial role in systemic lupus erythematosus and antiphospholipid syndrome. Russian rheumatology, under the leadership of academician Valentina Alexandrovna Nasonova, greatly contributed to the research of these disorders. This article addresses the current view about the overlapping pathogenetic mechanisms of thrombosis in systemic lupus erythematosus and antiphospholipid syndrome, the relevance of these studies during the COVID-19 pandemic, and the prospects for antithrombotic and anti-inflammatory therapy.

Terapevticheskii arkhiv. 2023;95(5):365-374
pages 365-374 views

Original articles

Subclinical atherosclerosis of the carotid arteries in patients with rheumatoid arthritis with low cardiovascular risk

Gerasimova E.V., Popkova T.V., Shalygina M.V., Kirillova I.G., Gerasimova D.A., Glukhova S.I., Nasonov E.L.

Abstract

Aim. To evaluate the detection rate of subclinical carotid atherosclerosis in rheumatoid arthritis (RA) patients with low cardiovascular risk (CVR).

Materials and methods. The study included 182 RA patients with low CVR (mSCORE<1%) and no established cardiovascular diseases and a control group comprising 100 people. Atherosclerotic lesion of the carotid arteries was assessed using Doppler ultrasound of the carotid arteries and was determined by the detection of atherosclerotic plaque (ASP) – the local increase in the thickness of the intima-media complex (IMT) >1.5 mm.

Results. Carotid ASP were observed more frequently in RA patients with low CVR than in the control group (17% versus 8%; p=0.02). The frequency of ASP in RA patients with low CVR did not depend on the disease’s stage or activity and ongoing therapy. In RA, the detection of subclinical atherosclerosis was associated with traditional risk factors: carotid ASP were detected 4 times more often in men than in women (48% versus 12%, p<0.01); carotid IMT correlated with age (R=0.46), body mass index (R=0.17), LDL-C level (R=0.20), systolic blood pressure (R=0.17); p<0.05 in all cases. According to a multivariate model, in RA, the risk of developing ASP increased in the presence of dyslipidemia (odds ratio – OR 2.97; 95% confidence interval – CI 1.36–6.49; p=0.006) and arterial hypertension (OR 2.16; 95% CI 1.03–4.54; p=0.04). In RA patients with carotid ASP, sCD40L level was associated with carotid IMT (R=0.32; p=0.04) and cholesterol concentration (R=0.39; p=0.01).

Conclusion. Subclinical atherosclerotic lesions of the carotid arteries were observed in 24% of RA patients with low cardiovascular risk and were detected almost 2 times more often than in the control group. In RA patients with low CVR, the risk of developing carotid ASP increased by 2–3 times with concomitant hypertension and dyslipidemia. The carotid IMT was associated with traditional risk factors – age, gender, lipid levels and blood pressure indicators, in cases of detection of ASP – with an immunoinflammatory marker – sCD40L.

Terapevticheskii arkhiv. 2023;95(5):375-379
pages 375-379 views

Long-term use of glucocorticoids in patients with active rheumatoid arthritis: therapeutic "freeze frame"

Gordeev A.V., Matyanova E.V., Galushko E.A.

Abstract

Background. In Russia, as well as throughout the world, the use of glucocorticoids (GC) in the treatment of rheumatoid arthritis (RA) is widespread, often going beyond the recommendations for both duration and dose regimen, which makes it relevant to study the long-term consequences of such a “wrong” (EULAR, 2022) use of GC in RA therapy.

Materials and methods. Of 1143 patients with active RA (ACR/EULAR 2010), two groups were formed: A (n=782) RA patients with more than 6 months of experience with systemic GC; group B (n=245) – no experience of taking GC. The cumulative disease index (CIRS) was used to assess the comorbidity profile.

Results. Patients in group A were older (p<0.0001), with a longer duration of RA (p=0.0004) and more often with IV radiological stage (p=0.02). With comparable (DAS28) RA activity, the D2T variant of RA was more often detected in them (p=0.036). RA therapy in group A was characterized by a large number of used disease-modifying anti-rheumatic drugs (p=0.0003), more frequent development of methotrexate-induced hepatitis (p=0.03). In group A, the time interval between the onset of RA and the initiation of biological therapy was longer (p=0.0001) and directly correlated with the duration of GC therapy (Rs=0.38) with a comparable qualitative structure of the used b/tsDMARDs. In the same group, tuberculosis, hypertension, chronic kidney disease, cataract and osteoporosis (p<0.05) and its complications were diagnosed significantly more often with a comparable frequency of cardiovascular disease, diabetes, and gastrointestinal lesions. In group A, a higher CIRS multimorbidity index was detected, and the CIRS severity index was lower than in group B (p<0.05).

Conclusion. Long-term use of GC did not lead to a decrease in disease activity, inhibition of radiographic progression, delayed the timely administration of b/tsDMARDS and was accompanied by an increase in the multimorbid load.

Terapevticheskii arkhiv. 2023;95(5):380-385
pages 380-385 views

Mental disorders in patients with systemic lupus erythematosus: association with activity and the course of rheumatic disease

Borisova A.B., Lisitsyna T.A., Veltishchev D.Y., Reshetnyak T.M.

Abstract

Aim. To clarify the relationship between the clinical and psychopathological features of mental disorders, clinical and laboratory manifestations of activity and the nature of the course of systemic lupus erythematosus (SLE).

Materials and methods. The study included 119 patients – 98 (82.4%) women, mean age 36.5±12.4 years (M±SD) – with a reliable diagnosis of SLE (EULAR/ACR 2019 criteria), 51 (29.5%) of them – with secondary antiphospholipid syndrome – APS (International criteria of 2006).

Results. Among patients with SLE a high frequency of anxiety-depressive spectrum disorders (ADSD) and cognitive impairment (CI) was revealed. There was an association of greater severity of depression with high SLE activity index, acute/subacute onset of the disease course according to the classification of V.A. Nasonova, relapsing-remitting and chronic active current disease activity patterns of SLE according to the classification of S. Barr – M. Petri. Anxiety disorders were associated with subacute onset and relapsing-remitting disease activity patterns of SLE and were not associated with SLE activity index. Bipolar disorder was detected more often in patients with chronic SLE. Acute psychosis/delirium was associated with acute onset of SLE. Organic CI was associated with APS, chronic onset and long quiescent disease activity patterns of SLE. The episindrome and schizotypal disorder in patients with SLE are more often caused by concomitant APS.

Conclusion. Patients with high SLE activity index should be of particular concern to rheumatologists regarding the diagnosis of depressive disorders. Patients with concomitant APS need timely diagnosis and treatment of CI and episindrome in order to improve the prognosis of the disease and the overall quality of life.

Terapevticheskii arkhiv. 2023;95(5):392-397
pages 392-397 views

Physical activity and nutritional status in women with rheumatoid arthritis and sarcopenic phenotype of body composition

Dobrovolskaya O.V., Feklistov A.Y., Demin N.V., Kozyreva M.V., Toroptsova N.V.

Abstract

Aim. To assess physical activity (PA) and nutritional status and their relationship with the sarcopenic phenotype of body composition in women with rheumatoid arthritis (RA).

Material and methods. 104 women (mean age 59.5±8.7 years) with RA underwent clinical and laboratory examination, dual-energy X-ray absorptiometry. The level of PA and nutritional status were assessed using the International Physical Activity Questionnaire (IPAQ) and Mini Nutritional Assessment (MNA) questionnaires, respectively.

Results. Sarcopenic phenotype was diagnosed in 37.1% of patients. Moderate and low PA levels were detected in 44.2 and 7.8%, respectively, risk of malnutrition – in 50% of persons. In multivariate logistic regression analysis, factors associated with the sarcopenic phenotype were determined: the frequency of vigorous PA<3 times a week [odds ratio – OR 5.12 (95% confidence interval – CI 1.15–22.94); p=0.032], walking <1 hour a day [OR 4.98 (95% CI 1.14–21.74); p=0.033], risk of malnutrition by MNA [OR 4.13 (95% CI 1.12–15.32); p=0.034], body mass index <25 kg/m2 [OR 8.11 (95% CI 1.86–35.32); p=0.006] and daily calcium intake <500 mg [OR 4.62 (95% CI 1.06–20.08); p=0.041].

Conclusion. 52% of women with RA had moderate оr low PA levels, and 50% of patients were at risk of malnutrition. The risk of sarcopenic phenotype associated with a low frequency of vigorous PA, low walking time, risk of malnutrition, body mass index <25 kg/m2 and insufficient calcium intake.

Terapevticheskii arkhiv. 2023;95(5):398-403
pages 398-403 views

Diastolic dysfunction of ventricles in patients with calcium pyrophosphate crystal deposition disease while receiving anti-inflammatory therapy

Eliseev M.S., Zheliabina O.V., Kirillova I.G., Korsakova Y.O.

Abstract

Background. Calcium pyrophosphate crystal deposition disease (CPPD) may be associated with developing of diastolic dysfunction (DD).

Aim. To determine the variability of echocardiographic parameters in patients with CPPD receiving anti-inflammatory therapy.

Materials and methods. Twenty six patients with CPPD and osteoarthritis (OA) from 18 to 65 years old were included in the case-control study. All patients underwent echocardiography, laboratory parameters at baseline and after 6 months. Patients with CPPD received methotrexate 15 mg per week or hydroxychloroquine 200 mg once a day, or colchicine 1 mg per day. Diastolic function according to echocardiography was assessed.

Results. Diastolic dysfunction was detected in 19 patients: in 11 (42%) patients with CPPD and 8 (31%) patients with OA (p=0.39). The baseline serum CRP level was higher in the CPPD group (p=0.03), no differences were found for other indicators. Twenty-two patients with CPPD and 19 patients with OA completed the study. In patients with OA, there were no significant changes in indicators reflecting the diastolic function of ventricles.

Conclusion. CPPD therapy with colchicine, hydroxychloroquine and methotrexate has a positive effect on indicators of diastolic ventricular function.

Terapevticheskii arkhiv. 2023;95(5):386-391
pages 386-391 views

A new integral enthesial-comorbididity index of psoriatic arthritis activity

Korsakova Y.L., Korotaeva T.V., Loginova E.Y., Gubar E.E., Vorobyeva L.D., Glukhova S.I., Nasonov E.L.

Abstract

Aim. To develop an integral index of psoriatic arthritis (PsA) activity.

Materials and methods. 117 patients with PsA (M/F – 63/54) were included. Patients’ age 44±11 years, psoriasis (Ps) duration – 213±153 months, PsA duration – 73.4±78.5 months. Patients underwent standard clinical examination of PsA activity: tender (out of 68) and swollen (out of 66) joint counts (TJC, SJC), LEI, tenderness of the plantar fascia (PF), skin lesion severity (BSA), presence of nail Ps, body mass index (BMI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), DAPSA, FACIT-F. Parametric and nonparametric statistic methods, correlation and ROC analysis were used.

Results. Mean DAPSA was 38±21, TJC – 14.2±10.6, SJC – 10.6±8.3, ESR – 30.5±29.5 mm/h, CRP – 23.3±29 mg/l, LEI – 1.2±1.5, FACIT-F – 32±11, BMI – 27.4±6.2 kg/m2. The following significant positive correlations were revealed: between DAPSA and BMI, patients’ age, ESR, PsA and Ps duration, TJC, SJC, LEI, presence of PF enthesitis, skin lesion severity, presence of nail Ps. A negative correlation between FACIT-F and male sex was found. Based on the predictive model of parameters, the Entesial-Comorbid Index of PsA (ECIPsA) was created: 3.81×LEI+13.72×PF+0.54×Age-0.25×FACIT-F+7.36×BSA+7.94×PsA duration+5.5×Nail Ps+0.32×BMI-3.52, namely LEI – Leeds Enthesial Index; PF – pain in the PF; patient’s age; FACIT-F – fatigue scale; BSA<3%=0, ≥3%=1; PsA duration≤2 years=0, >2 years=1; presence of nail Ps=1, absence=0; ECIPsA≥28 corresponds with high PsA activity according to DAPSA≥28. ROC analysis of sensitivity and specificity of the prognostic model demonstrated high correctness of the index: the area under the ROC curve was 0.768, 95% confidence interval (0.624–0.913).

Conclusion. The new PsA activity index corresponds to the existing ones and takes into consideration the clinical heterogeneity and comorbidity of the disease.

Terapevticheskii arkhiv. 2023;95(5):404-409
pages 404-409 views

Comparative assessment of sensitivity and specificity of three variants of classification criteria for systemic lupus erythematosus in a cohort of Russian patients

Reshetnyak T.M., Lisitsyna T.A., Cheldieva F.A., Shumilova A.A., Glukhova S.I., Starovoytova M.N., Seredavkina N.V., Desinova O.V., Verizhnikova Z.G., Nasonov E.L.

Abstract

Background. The clinical and serologic heterogeneity of systemic lupus erythematosus (SLE) presents challenges for diagnosis, particularly in the earliest stages of the disease when there are insufficient signs to make a reliable diagnosis.

Aim. To make a comparative assessment of sensitivity and specificity of various classification criteria of SLE on a cohort of patients of Nasonova Research Institute of Rheumatology.

Materials and methods. A total of 252 patients were included in the study; 152 (60%) of 252 patients had reliable SLE (mean age 36 [29.5–46] years, duration of disease 9 [3.4–19] years). Of 252 patients, 26 (11%) had PAPS (mean age 36.5 [31–42] years, duration of disease 4.6 [1–10.4] years). Systemic sclerosis was diagnosed in 74/252 (29%) patients, (mean age 51.5 [42–59] years, duration of disease 9 [5–16] years). The quality of the classification function of the criteria was assessed by ROC analysis.

Results. SLE was diagnosed in 131 (86%) of 152 patients using the American College of Rheumatology – ACR)-1997 criteria, in 145 (95%) using the The Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria, and in 144 (94.7%) using the European League Against Rheumatism (EULAR)/ACR 2019 criteria. ANF positivity was the least statistically significant of all signs in relation to the diagnosis of SLE. The area under the curve (AUC) for ANF≥1/160 titers was AUC 0.654 for the ACR-97 criteria, AUC 0.616 for the SLICC-12 SLE criteria, and AUC 0.609 for the 2019 EULAR/ACR criteria. ROC analysis of the relationship between the number of criteria/points and a reliable diagnosis of SLE revealed a high diagnostic accuracy – the AUC for all SLE criteria was greater than 0.940. In the ROC analysis of patients with SLE and PAFS, indicating the number of diagnostic criteria, sensitivity was 86% for ACR-1997, 95% for SLICC-2012, 95% for EULAR/ACR 2019, and specificity was 100, 62 and 62%, respectively.

Conclusion. The classification criteria SLICC-2012 and EULAR/ACR 2019 are more sensitive for the diagnosis of SLE in the Russian population, and the criteria ACR-1997 are more specific. All three variants of the SLE classification criteria have sufficient sensitivity and specificity for their use in real clinical practice.

Terapevticheskii arkhiv. 2023;95(5):410-417
pages 410-417 views

The structure of post/long COVID fatigue syndrome. Prospects for correction

Kuznetsova P.I., Tanashyan M.M., Raskurazhev A.A., Zaslavskaya K.I.

Abstract

Aim. To study the features of post-COVID asthenic syndrome and evaluate the effectiveness of the drug containing the succinic acid complex with trimethylhydrazinium in its treatment.

Materials and methods. A prospective, multicenter, comparative, randomized, double-blind, placebo-controlled study of the efficacy of sequential therapy with BRAINMAX® included 160 patients with a history of coronavirus infection within 12 to 16 weeks (not more than 12 months). The study was conducted at 6 healthcare centers in different regions of the Russian Federation. Testing was performed on the following scores: VAS for headache score, MFI-20 asthenia score, PSQI test, FAS-10 fatigue score, DHI dizziness score, MoCA cognitive impairment score, Beck anxiety score, vegetative index of Kerdo.

Results. PSQI questionnaire showed significant improvement in sleep quality in the study group: by -2.5 points [-4; -1] (p<0.001); there was a more pronounced significant decrease in the MFI-20 score of -19.5 points [-27; -11] (p<0.001); a significant decrease in the FAS-10 fatigue score by -9 [-13.5; -4] points (p<0.001); DHI dizziness score showed a decrease by -6 [-12; 0] points in the BRAINMAX® group (p=0.001); the score of Beck anxiety and depression scale decreased by -5 [-11; -2] points (p<0.001). Multiple linear regression data showed a significant increase of 0.56 (p=0.02) in the MoCA score.

Conclusion. Our study convincingly showed the effectiveness of therapy with BRAINMAX® in a wide range of symptoms in patients with the post-COVID syndrome.

Terapevticheskii arkhiv. 2023;95(5):418-424
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Clinical notes

AL amyloidosis mimicking IgG4-related disease: case report

Chaltsev B.D., Torgashina A.V.

Abstract

The article describes a unique clinical case of AL amyloidosis mimicking IgG4-related disease. Plasma cell dyscrasias can mimic clinical and laboratory manifestations of rheumatic diseases, which can lead to a delay in diagnosis and inappropriate therapy.

Terapevticheskii arkhiv. 2023;95(5):425-428
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Reviews

Hypogonadism syndrome in men with inflammatory joint diseases: A review

Panevin T.S., Rozhivanov R.V., Nasonov E.L.

Abstract

Most rheumatic diseases are characterized by sexual dimorphism both in prevalence and in the characteristics of the clinical course. Increased production of pro-inflammatory cytokines that accompanies inflammatory joint diseases may be accompanied by a decrease in the level of male sex hormones, and vice versa, the presence of hypogonadism in men increases the risk of developing certain rheumatic diseases. The review presents data on the relationship between testosterone deficiency and major inflammatory joint diseases, as well as the effect of testosterone replacement therapy on their manifestations.

Terapevticheskii arkhiv. 2023;95(5):429-434
pages 429-434 views

The use of sodium hyaluronate to treat upper limb disease: A review

Filatova Y.S., Ilyin M.V.

Abstract

The most common diseases of the upper limb are osteoarthritis (OA) of the joints of the hands, lateral epiconlitis, tendinitis of the shoulder muscles, adhesive capsulitis. OA of the shoulder and acromioclavicular joints is less common. The development of acute and subacute pain in the elbow and shoulder joints in the vast majority of cases is determined by the pathology of soft tissues: muscles, ligamentous apparatus and related synovial bags, making it difficult to diagnose. A clinical and radiological heterogeneity of OA of the joints of the hands is a very complex pathology for the study, and also to create a unified algorithms for therapy. Therapy nonsteroidal anti-inflammatory drugs are effective in the short term, but it has several side effects. Despite a variety of attempts at therapy with successful and unsuccessful outcome, the attention of researchers for several decades converted to the injection therapy with hyaluronic acid. The article presents the data of studies demonstrating the anti-inflammatory effect of hyaluronic acid in the treatment of OA, as well as the results of clinical trials and data system of meta-analysis demonstrating the effectiveness of intra-articular and extra-articular therapy tendinopathy of the upper limb. Most of the cited studies demonstrated the efficacy and good tolerance of 1% sodium hyaluronate. In the domestic market it is presented in the drug Flexotron Forte. The authors provide the results of the study results, demonstrating the efficacy and safety of using Flexotron Forte to clinical practice.

Terapevticheskii arkhiv. 2023;95(5):438-443
pages 438-443 views

Structural and functional characteristics of the brain and their role in the development of eating behaviour in obesity: A review

Samoilova I.G., Podchinenova D.V., Matveeva M.V., Kudlay D.A., Oleynik O.A., Tolmachev I.V., Kaverina I.S., Vachadze T.D., Kovarenko M.A., Loginova O.A.

Abstract

Obesity is a major public health problem that requires new approaches. Despite all interventions, the behavioural and therapeutic interventions developed have demonstrated limited effectiveness in curbing the obesity epidemic. Findings from imaging studies of the brain suggest the existence of neural vulnerabilities and structural changes that are associated with the development of obesity and eating disorders. This review highlights the clinical relevance of brain neuroimaging research in obese individuals to prevent risky behaviour, early diagnosis, and the development of new safer and more effective treatments.

Terapevticheskii arkhiv. 2023;95(5):434-437
pages 434-437 views

History of medicine

Rheumatoid factor: study history and concept evolution

Guliaev S.V., Strizhakov L.A., Moiseev S.V.

Abstract

Rheumatoid factor became the first laboratory marker of rheumatoid arthritis and one of the first serological markers used to recognize the major autoimmune diseases. Details of the discovery with special regard to contribution of E. Waaler and H. Rose are presented in this historical review. Same assays used to exam the rheumatoid factor, its frequency and modern view on diagnostic significance in different diseases are described in this article.

Terapevticheskii arkhiv. 2023;95(5):444-446
pages 444-446 views


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