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Rheumatology Science and Practice

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Vol 58, No 5 (2020)
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FRONTIERS

469-479 3666
Abstract
The clinical presentation and outcomes of infection with the novel coronavirus (COVID-19) are characterized by exceptional variability in manifestations, which depend on many factors, one of which is the patient’s age. One of the severe life-threatening manifestations in adults is severe acute respiratory syndrome (SARS-CoV-2), in some cases accompanied by the development of multiple organ failure. During the first two to three months of the COVID-19 pandemic, the global medical community was of the opinion that this disease in children is usually mild and not fatal. However, with the accumulation of new information, it became clear that there is a growing recognition of the existence of multisystem inflammatory syndrome in children, chronologically associated with SARS-CoV-2, which can lead to serious consequences. The article presents the main epidemiological, clinical and laboratory characteristics of the syndrome, as well as discusses the issues of its pathogenesis, differential diagnosis with a number of other acute conditions associated with an dysbalance of cytokines.

ORIGINAL RESEARCH

480-488 2257
Abstract

Netakimab (NTK) is a humanized anti-interleukin-17А (IL-17A) monoclonal antibody approved for the treatment of psoriatic arthritis, ankylosing spondylitis, moderate to severe psoriasis. Here, we present the results of the 24-weeks double blind period of the PATERA study.

Objective. The objective of the study was to evaluate the efficacy and safety of NTK compared to placebo in patients with psoriatic arthritis (PsA).

Patients and methods. 194 patients with active PsA with an inadequate response to previous therapy with nonsteroidal anti-inflammatory drugs, conventional or biologic disease-modifying antirheumatic drugs, were randomized in a 1:1 ratio to receive subcutaneous 120 mg NTK or placebo at weeks 0, 1, 2, 4, 6, 8, 10, 14, 18, 22. At week 16 ACR20 (20% improvement in the American College of Rheumatology response criteria) non-responders in placebo group were reassigned to NTK in a blinded manner. The primary endpoint was the proportion of patients achieved ACR20 response at week 24.

Results. 82,5% of patients in the NTK group and 9.3% of patients in the placebo group achieved ACR20 at week 24 with the 95% CI [0,63; 0,84] (p < 0,0001). Skin manifestations and axial disease significantly improved with NTK. The safety profile of NTK was comparable to placebo. The most frequent treatment-related AEs were expected and common for all other IL-17 inhibitors: increased alanine aminotransferase (ALT), infections, lymphopenia.

Conclusion. NTK in the dose of 120 mg has superior efficacy over placebo in patients with active psoriatic arthritis. The safety profile is consistent with other IL-17 inhibitors.

489-494 1207
Abstract

Objective. To evaluate the prevalence of traditional risk factors in systemic lupus erythematosus (SLE) patients, assess the 10-years risk of developing type 2 diabetes mellitus (DM) in SLE patients and identify those necessitating preventive interventions following altered glucose metabolism using the Finnish Type 2 Diabetes Risk Score (FINDRISK) questionnaire.

Materials and methods. The study included 119 SLE patients (107 women, 12 men, with median age 39 [33; 47] years and mean disease duration 6 [1,12] years.
The control group included 100 age and sex matched individuals without immune-mediated inflammatory rheumatic diseases and without previous DM history. The 10-years risk of developing type 2 DM in SLE patients and the controls assessed using the Russian adaptation of Finnish Type 2 Diabetes Risk Score questionnaire. Fasting glucose levels in venous blood were measured in all SLE patients. Glucose levels ≥6.1 mmol/L were interpreted as fasting hyperglycemia.

Results. The prevalence of traditional type 2 DM risk factors in SLE patients was as follows: abdominal obesity was found in 63.9%, lack of physical activity – in 62.2%, intake of antihypertensive drugs— in 52.9%, BMI ≥25 kg/m2 in 42.0%, unhealthy diets – in 40.3%, family history of DM – in 35.3%, age over 45 years – in 32.8%, history of hyperglycemia episodes – in 15.1%. Abdominal obesity and intake of antihypertensive drugs were more often documented in SLE patients, while all other risk factors were equally represented in SLE and control groups. On average 3 [2; 5] risk factors were found in each SLE patient. Low type 2 DM risk was a more rare phenomenon in SLE patients vs healthy controls (36.1 and 51%, р<0.05). Primary type 2 DM prophylaxis recommended in case of moderate, high and very high risk was more often indicated in SLE vs the healthy controls (29.4 and 17.0%, р=0.03), including those younger than 45 years (18.3 and 6.1% respectively, р=0.05). Fasting hyperglycemia was found in 1.2% patients with low-slightly increased type 2 DM risk and in 16.1% individuals with moderate, high and very high risk (p=0.04).

Conclusions. High prevalence of such traditional type 2 DM risk factors as abdominal obesity, lack of physical activity and intake of antihypertensive drugs was demonstrated in SLE patients. Finnish Type 2 Diabetes Risk Score questionnaire identified moderate, high and very high 10-year risk of developing type 2DM in 29.4% SLE patients, necessitating prophylactic interventions in view of altered glucose metabolism.

495-502 641
Abstract
High prevalence in different age groups, a significant decrease in patient’s quality of life, and potentially unfavorable outcomes, especially in association with comorbid pathologies define the medico-social significance of psoriasis. The article analyzes the clinical and anamnestic data obtained within the program of medical and social support of patients with psoriasis (PsO) and / or high-to-moderate severity psoriatic arthritis (PsA) “Take control of psoriasis”, launched by ROOI “Human Health” in the conjunction with the Interregional Charitable Public Organization “Skin and Allergic Diseases”. The study involved 20 physicians (8 dermatologists and 12 rheumatologists) from 11 cities and regions of Russia. The program lasted for 3 months and included one-time epidemiologic data collection of 564 patients and educational sessions, aimed to inform patients about their disease features, risk factors, and current international approaches to diagnostics. Every third patient demonstrated the features of both – psoriatic arthritis and psoriasis, established by two specialties – dermatologists and rheumatologists co-existing PsO+PsA in the majority of patients (94%). Patients with various forms of PsO and PsA had comorbid conditions, with prevailing cardiovascular, endocrine and metabolic disorders. Cardiovascular diseases prevailed in the structure of comorbid pathology showing 44% incidence, followed by endocrine disorders (metabolic syndrome, diabetes mellitus) diagnosed in 23% sometimes associated with other diseases in a proportion of patients; 37% patients were overweight or obese based on BMI, especially those receiving biologics. 58% and 49% of patients in the age group of 45–59 years received biologic therapy under the supervision of dermatologists and rheumatologists, respectively. In contrast, patients aged 18–44 years were more likely to be on biologic therapy administered by a rheumatologist – 43%, with only 27% treated by dermatologists. Among all patients on biologic therapy dermatological patients’ mean age was 47.95 years and rheumatological – 40.84 years. Therapy with biologics made it possible to achieve PASI 75 in PsO and minimal disease activity in PsA significantly more often (in 95% and 72% of patients) than therapy with conventional DMARDs / tsDMARD (in 43% and 27%) and other types of therapy (in 64% and 14%, respectively).
503-511 838
Abstract

Objective: Assessment of ankylosing spondylitis activity patterns during pregnancy using BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score — C-Reactive Protein) disease activity indices.

Materials and methods. The prospective study included 36 pregnant women with AS (modified New York AS criteria, 1984). Patients’ mean age was 31.6±4.8 years, mean age at AS onset was 21.8±10.9, and disease duration 134.9±89.3 months. The control group included 30 healthy pregnant women with no history of back pain and arthritis, their mean age was 28.2±4.5 years. In the I trimester of pregnancy 10 (33.3%) As patients experienced back pain, while in the III trimester already 15 (50%) had back pain. Throughout pregnancy, the intensity of back pain in the I, II и III trimesters based on numeric scale was on average 1.9±0.9; 2.1±1.1 and 2.1±0.8. BASDAI and ASDAS-CRP were used to measure disease activity on gestational Weeks 10–11, 20–21 and 31–32. The time of conception BASDAI score was assessed retrospectively at the 1st visit.

Results and discussion. BASDAI mean values at the time of conception and I, II и III trimesters of pregnancy were: 2.3±1.9; 2.8±1.72 (p<0,05 vs month of conception); 3.2±1.9 and 3.3±2.1 respectively. Mean ASDAS-CRP in the I, II и III trimesters were 1.9±0.7; 2.3±0.9 and 2.2±0,8 respectively. There was a trend to CRP increase in the II and III trimesters vs the I: median CRP values in the I, II and III trimesters were 5.7 [1.6; 6.2], 8.0 [2.1; 9.6] and 7.9 [2.0; 9.2] mg/L, respectively. Percentages of patients with high disease activity based on BASDAI scores in the I, II and III trimesters were 30.6; 34.3 and 34.3%; based on ASDAS-CRP — 36.1; 57.5 and 53%, respectively. Throughout pregnancy, BASDAI scores were lower in the control group than in AS patients (p<0.01). However, no differences were found when comparing BASDAI values of AS patients and healthy women with back pain during pregnancy. The level of fatigue did not differ between pregnant women with AS (median 5[3; 7] and 5[3; 6]) and healthy controls (5[3; 8] and 5[4; 6]) in the I and II trimesters, while in the III trimester, fatigue in healthy pregnant women (6[4; 8]) was more pronounced than in AS patients (5[3; 6], p=0.01). Throughout pregnancy, the intensity of back pain in AS patients and healthy pregnant women with back pain did not differ (p<0.05). Median pain intensity in the I, II and III trimesters was 3[2; 4]; 4[3; 5]; 3[2; 6] and 2,5[1; 4]; 3[2; 7]; 4[2; 6], respectively. A high (rs ≥0,7) correlation of all BASDAI components with the index itself in each trimester of pregnancy, except for joint pain in the month of conception, and in the I and III trimesters was established in the group of pregnant women with AS. The control group had quite high correlation (rs >0.7) of fatigue severity with the BASDAI index in the I and II trimesters of pregnancy and moderate correlation (rs >0.53) in the III trimester; as wells as moderate (rs >0.5-0.69) correlation between back pain and BASDAI

Conclusion. A trend towards increasing AS activity based on BASDAI and ASDAS-CRP scores and CRP levels was established for the first half of pregnancy. Later in pregnancy these increased values failed to return to normal until the end of gestation. The percentage of AS patients with highto-moderate disease activity throughout pregnancy was lower based on BASDAI score vs based on ASDAS-CRP. Some BASDAI components (fatigue and back pain) reflect not only the activity of AS, but also changes associated with physiological pregnancy. The BASDAI index requires adaptation for use in pregnancy

512-519 864
Abstract

Cardiovascular risk (CVR) in patients with calcium pyrophosphate crystal deposition disease (CPPD) has not been studied, and the optimal method for assessing it has not been established yet.

Objective: Evaluation of CVR and comparison of results using Adult Treatment Panel III (ATP III) and Reynolds Risk Score (RRS) scales in patients with CPPD, gout, rheumatoid arthritis (RA) and in the control group.

Materials and methods: Cross-sectional, single-center study performed by case-control method. There are 42 patients with CPPD in main group, 42 patients with gout and RA in the comparison groups are, 42 healthy volunteers in the control group. The survey included measurements of anthropometric measures, blood pressure (BP), serum glucose, creatinine, cholesterol (TC), high density lipoproteins (HDL), low density lipoproteins (LDL), C-reactive protein (CRP). CVR was assessed on ATP III and RRS scales, comparison of its evaluation results was carried out between groups and between scales within groups.

Results and discussion: Most of the parameters in the compared groups did not differ. However, HDL CS levels were significantly higher in patients with CPPD and in the control group than in RA and gout (p<0.05). In addition, in patients with gout and RA, systolic BP was higher than in CPPD and in control (p<0.05).
CRP in CPPD was lower than in gout and RA and was not significantly different from this indicator in the control group. Its median was 3.8 [1.0; 12.4], 8.5 [4.1; 12.9] (р <0.05), 8.6 [4.1; 20.6] (р<0.05), 1.5 [0.8; 2.6] mg/l (p>0.05). The CRP > 5 mg/L in CPPD and in the control group was greater than in RA (p<0.05) and gout (p<0.05), but CRP≥5 mg/L was determined in 18 patients (43%) with CPPD and only in 3 (7%) people in the control group (p<0.05). A high and very high risk of cardiovascular disease (CVD) on the ATP III scale in CPPD was noted in 5 (12%) in gout – in 7 (17%), in RA – in 9 (21%) and in the control group – in 8 (19%) cases. Its frequency in all groups was comparable.
A high and very high risk of CVD for RRS was identified in 9 (21%), 14 (33%), 12 (29%) and 7 (17%) cases, respectively.

Conclusions: CVR under CPPD, RA and gout is comparable and quite high. The RRS scale may be a more objective method of assessing CVD risk in patients with CPPD, gout and RA.

PROGRESS IN RHEUMATOLOGY IN THE XXI CENTURY

520-531 1379
Abstract
A significant progress has been made in recent years in management of severe systemic scleroderma (SSD) manifestations, such as Raynaud’s phenomenon, renal crisis, and pulmonary arterial hypertension, subsequently improving survival and quality of life. At the same time, treatment algorithms for interstitial lung damage in SSD have not yet been developed. The review provides relevant information on therapeutic efficacy of drugs with various mechanisms of action, including immunosuppressive drugs (cyclophosphamide, mycophenolate mofetil, etc.), and high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation. New drugs with antifibrotic activity, including recently marketed in Russia nintedanib for treatment of interstitial lung diseases in SSD, as well as perspectives for potential use of biologics (rituximab, tocilizumab, etc.), and lung transplantation are considered separately.
532-543 981
Abstract
The explanation of the mechanisms underlying the pathogenesis of rheumatoid arthritis (RA), along with the development of a wide range of biologics (bDMARDs), is among the major achievements of medicine in the 21st century. A new direction in the pharmacotherapy of inflammatory rheumatic diseases is associated with the development of “targeted” oral anti-inflammatory drugs, which include Janus kinase (JAK) inhibitors. One representative of the class of JAK inhibitors is upadacitinib (UPA), which has been registered for the treatment of RA and is undergoing clinical studies in patients with ankylosing spondylitis, psoriatic arthritis, and other inflammatory rheumatic diseases. This review presents new data on the efficacy and safety of UPA in RA.

REVIEWS AND LECTURES

544-549 1217
Abstract
The article presents information about a rare hereditary disease – primary hypertrophic osteoarthropathy with autosomal dominant and autosomal recessive inheritance. Genetic heterogeneity is responsible for the clinical polymorphism of symptoms that appear in childhood and adolescence. Differential diagnosis should be carried out with secondary hypertrophic osteoarthropathy, which occurs in 90% of cases and is associated with malignant neoplasms, rheumatic diseases and other diseases. X-ray signs are of great importance to clarify the localization, extent and nature of bone lesions. There is no specific treatment for the disease.
550-559 690
Abstract
Systemic vasculitis (SV) associated with anti-neutrophilic cytoplasmic antibodies is a multifactorial process characterized by the variability of the epitope specificity of anti-neutrophilic cytoplasmic antibodies and the diversity of clinical phenotypes of the disease. In recent years, there has been an increasing interest in the combination of AAV and the phenomenon of IgG4 hyperproduction, which varies widely within AAV, from anti-neutrophilic cytoplasmic antibodies products of IgG4 subclass of undetermined significance, the presence of IgG4 positive plasma cells in the foci of immunoinflammatory lesions in patients with a definite diagnosis of AAV, to the typical clinical manifestations of an IgG4-related disease (IgG4-RD). We introduce own clinical case and analyze the combined data of the literature, which included 35 cases of a combination of AAV and IgG4-related pathology, indicating existing differences in the clinical manifestations of classical IgG4-RD and when combined with AAV. The currently accumulated data allows us to discuss the allocation of a specific clinical and immunological variant of AAV with IgG4 hyperproduction, characterized by a combination of clinical manifestations of AAV and clinical and / or histological signs of IgG4-related pathology. It is important to emphasize that the allocation of phenotypes of AAV in the future may be important for the personalized choice of treatment tactics for patients.

ORTHOPEDIC RHEUMATOLOGY AND REHABILITATION

560-569 17727
Abstract

Aim: to evaluate the effectiveness of hyaluronic acid (HA) preparations with different molecular weights and in combination with chondroitin sulfate (HS) for intra-articular (IA) injections in the treatment of patients with stage I–III knee OA.

Subjects and methods. IA HA injections were performed 160 patients with primary and post-traumatic knee OA of the I–III stages at the department of traumatology-orthopedics, V.A. Nasonova Research Institute of Rheumatology for the period from September 2017 to June 2019. Patients were divided into 4 groups. Group 1 consisted of 80 patients treated with low molecular weight (LMW) HA, group 2–20 patients treated with medium molecular weight (MMW) HA, group 3–30 patients treated with high molecular weight (HMW) HA, and group 4–30 patients who were intraarticular introduced HA with HS. The course of IA injections was 2 for LMW, HMW, and HA with HS, and 3 for MMW HA. Injections were performed with an interval of 1 week. To evaluate the results of treatment, we studied the intensity of pain according to VAS and the total score of KOOS before treatment and on follow-up examinations 1, 3 and 6 months after the course of IA HA injections.

Results. The maximum reduction in pain with IA HA injections at stage I of knee OA occurred by 3 months after the course of treatment. Moreover, improvement was detected by 1 month in 84.3% of cases, and remained until the end of the study in 71.1% of patients. All HA preparations used in stage I of knee OA were effective. At stage II of the knee OA after 3 months after the course of IA HA, different efficiencies of HA preparations were revealed. So, in the groups of LMW, MMW and HA with HS, the improvement persisted up to 3 months, and in the group of HMW HA – up to 1 month. After 3 months, the best results were shown by HA with HS, by 6 months the results were comparable. IA HA injections at the II stage of knee OA led to good and excellent results 1 month after the course of treatment in 53.9% of cases, but by the end of the study, improvement remained in only 30.8% of patients. In the case of the use of HA in stage III of the knee OA, the effectiveness of the studied drugs was comparable, and the maximum improvement was achieved by 1 month. The positive effect of IA HA injections in patients with stage III of the knee OA one month after the course of treatment was obtained in 40.6% of cases, by 3 months it decreased to 18.8%, and by 6 months – to 15.7% of patients.

Conclusions. IA injections of HA at stage I of the knee OA is a highly effective method of conservative treatment, which allows to relieve pain and improve the condition of the knee joint for a period of 6 months or more. The use of HA preparations at stage II of the knee OA allows reducing pain up to 3 months with IA injections of LMW and MMW HA, as well as HA with HS. HMW HA helps reduce pain intensity for a period of 1 month. The use of HA preparations in stage III of the knee OA leads to a short-term relief of symptoms of OA.

570-576 931
Abstract

Local injections of platelet-rich plasma (PRP) and hyaluronic acid (HLA) are considered an effective method for treating chronic shoulder pain (CSP) associated with damage to the tendons of the rotator cuff muscles (RCM).

The aim of the study is to compare the effectiveness and safety of local therapy of PRP and HLA in patients with CSP caused by damage to the tendons of the RCM muscles.

Materials and methods. The study included 100 patients (54% women and 46% men, average age 51.5±15.1 years) with CSP (persisting for ≥3 months) associated with damage and tendinitis of the supraspinatus, subacute, scapular or small round muscle, confirmed by magnetic resonance imaging or ultrasound (ultrasound). The patients were randomized into two groups of 50 people who were treated with PRP (three injections at 7-day intervals) or HLA (two injections at 7-day intervals). The injections were performed under ultrasound control in the subacromial SAC. The results of the study were evaluated by the dynamics of pain intensity (on a visual analog scale, up to 100 mm) and functional disorders (ASES and CSS indices) after 1, 3 and 6 months.

Results. Against the background of the use of PRP and HLA, there was a significant improvement in the condition of patients, while both drugs showed approximately the same effectiveness. The severity of VAS pain decreased from 56.8±15, respectively, after 6 months.5 and 57.6±17.8 mm to 31.8±27.8 and 30.2±26.3 mm, ASES-c 55.8±15.9 and 53.6±14.7 to 74.6±22.4 and 77.3± 22.4, CSS-c 59.2±14.4 and 47.8±16.9 to 69.9±17.3 and 65.6±19.2. the Dynamics of all these indicators in comparison with the baseline level was statistically significant (p<0.001). Number of patients with moderate / mild pain (<40 mm VAS) after 6 months. after the introduction of PRP and HLA was 48% and 60%, requiring regular NSAID intake 30% and 28%, respectively. In all parameters, the difference in the effectiveness of PRP and HLC was not statistically significant (p>0.05). The effectiveness of PRP and HLA (in terms of pain dynamics, ASES, and CSS) was significantly higher in individuals younger than 45 years, compared to older patients. The tolerability of therapy was good – after the introduction of PRP, 40% of patients had a short-term (3–4 days) increase in pain, which did not require the use of additional analgesics or interruption of treatment. No serious adverse reactions were observed when using PRP and HLA.

Conclusion. OTP and GLA are effective and safe in the treatment of CSP associated with damage to the tendons of the RCM muscles. The dynamics of pain intensity and functional status after the use of these drugs did not differ. Treatment of PRP and HLA is more effective in people younger than 45 years.

ABSTRACTS OF THE V EURASIAN CONGRESS OF RHEUMATOLOGY. MOSCOW 24–26 SEPTEMBER 2020



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