PROBLEMS OF RHEUMATOLOGY DURING THE 2019 CORONAVIRUS PANDEMIC
In mid-2021, the SARS-CoV-2 (Severe Acute Respiratory coronavirus 2) infection, which caused the coronavirus disease (COVID-19) pandemic, affected more than 157 million people in all regions of the world and led to more than 3.2 million deaths. It is assumed that elderly age, uncontrolled inflammation, anti-inflammatory therapy, comorbid pathology, genetic and other factors can potentially lead to an increase in “sensitivity” to viral and bacterial infections, including SARS-CoV-2. The new version of the recommendations of the Association of Rheumatologists of Russia formulates the main provisions concerning the tactics of managing patients with Immune-mediated Rheumatic Diseases during the ongoing COVID-19 pandemic.
Combating the consequences of COVID-19, a disease caused by the new coronavirus infection SARS-CoV-2, is a serious and very urgent task facing modern medicine. COVID-19 often has a severe course and is accompanied by multiple organ damage, systemic immune inflammation, coagulopathy, neuroendocrine and metabolic disorders. Even with a relatively favorable course, the consequences of SARS-CoV-2 infection can be degenerative changes in many organs (pulmonary fibrosis, cardiosclerosis), various functional and psychoemotional disorders. As a result, in 10–50% of patients, various unpleasant symptoms persist for a long time after the acute manifestations of COVID-19 subside and the virus is eliminated. This pathology is referred to as “post-COVID syndrome” (PCS). The main elements of PCS are chronic pain, fatigue, and psychoemotional problems. Functional disorders, autoimmune processes, and severe psychological distress after COVID-19 can cause the development and exacerbation of diseases characterized by chronic pain and fatigue, such as fibromyalgia and chronic fatigue syndrome. Therapy and prevention of PCS include correction of functional disorders, pain control, and consistent physical, psychological, and social rehabilitation.
The global diversion of health resources during the COVID-19 pandemic from the provision of routine medical care, and the more frequent and severe course of this infection in older patients justify the need to study the impact of the pandemic on the management of patients with osteoporosis.
Aim – to assess the impact of the COVID-19 pandemic on the management of patients with osteoporosis, as well as the impact of anti-osteoporotic drugs on the incidence of COVID-19.
Material and methods. A cross-sectional study was conducted, including a telephone survey and analysis of outpatient records of 304 patients with osteoporosis, who were recommended therapy with anti-osteoporotic medications. The average age was 70.8±8.8 years. The vast majority of patients took bisphosphonates in oral or parenteral forms.
Results. Problems with the timely conduct of laboratory tests were noted by 91 (30.4%) subjects, DXA testing – 98 (32.8%). 65 (22.1%) were unable to receive the drug in a timely manner. Problems were more common when taking parenteral drugs (p=0.002). The cumulative incidence of COVID-19 was 12.2%, which is twice as high as in the population. There was a tendency to a lower incidence of confirmed SARS-CoV-2 infection when treated with denosumab or zoledronic acid. COVID-19 cases were not associated with either a vitamin D dose or a 25(OH)D level.
Conclusions. During the COVID-19 pandemic, there is a significant decline in the quality of medical care for patients with osteoporosis, which cannot but lead to a new epidemic in the future – an epidemic of low-energy fractures. Our data confirmed the predisposition of older age groups to a higher incidence of COVID-19. However, there is no clear association of osteoporosis therapy with the risk of developing clinical manifestations of COVID-19.
ORIGINAL RESEARCH
Aim – to analyze long-term results of intensive treatment initiated at rheumatoid arthritis (RA) onset in real clinical practice.
Material and methods. 93 RA patients were included. Subcutaneous MTX was initiated at 10–15 mg per week with further dose escalation up to 20–30 mg per week. If MTX monotherapy did not allow to achieve treatment target of remission or low disease activity, biologics were added.
Results. Against the background of observation, there was a significant decrease in the activity of diseases and the level of acute phase indicators, after 12 months of treatment, the values of the DAS28-ESR indices were 2.76 [2; 3.7], SDAI – 5.34 [1.8; 9.7], CDAI – 5 [1.5; 9.5], corresponded to low disease activity; remission was achieved in 48.6%, low activity – in 17.5%, moderate activity remained in 31%, high activity – in 2.7% of patients. After 6 years the median age of patients was 58 [49; 66] years, the disease duration – 84 [79; 89] months, the low disease activity was documented in 21.3%, and remission – in 7.8% of patients. After 6 years, the value of the activity indices was: DAS28 – 4 [3.4; 4.59], SDAI – 15.06 [9.32; 21], CDAI – 15 [9; 21]; remission – in 7.7%, low disease activity – in 21.1%, moderate activity – in 60%, high activity – in 11.1% of patients.
Conclusion. Intensive therapy initiated at RA onset demonstrates high effectiveness, allowing to achieve remission/low disease activity in about 30% of patients. Adherence to this strategy allowed to discontinue biologics in and synthetic DMARDs after achieving treatment target.
Psoriatic arthritis (PsA) is a heterogeneous inflammatory arthritis associated with psoriasis (Ps); it belongs to the group of spondyloarthritis and is accompanied by damage to both the spine and peripheral joints, as well as the development of enteritis and dactylitis.
In addition to skin and joint damage, PsA has numerous comorbid conditions that are pathogenetically related to the underlying disease, such as inflammatory bowel disease (IBD) and autoimmune eye disease, as well as cardiovascular diseases, obesity and metabolic syndrome, diabetes, osteoporosis, malignancies, mental disorders, and various concomitant diseases. We present data of the prevalence of these pathological conditions among the cohort of PsA patients included in the Russian register.
Objective – to study the prevalence of comorbid and concomitant diseases in PsA patients.
Materials and methods. The Russian multicenter, observational study with retrospective and prospective data collection of PsA patients included 614 patients with the established diagnosis psoriatic arthritis, corresponding to the CASPAR criteria, from 39 subjects of the Russian Federation, female/male – 331 (54%)/283 (46%). The average age was 45.2±0.52 years, duration of PsA – 5.7±0.27 years, Ps – 15.71±0.56. Duration of observation period: January 2016 – November 26, 2019. The diagnosis of comorbid and concomitant diseases was confirmed by medical specialists in accordance with the ICD-10 code. The analysis of the frequency and structure (%) of these diseases was carried out.
Results. The majority of PsA patients had limited Ps: the area of Ps skin lesion (BSA, Basic Surface Area) was less than 3% in 372 (61.5%) patients, BSA from 3% to 10% – in 185 (30.6%), BSA>10% – in 47 (7.8%). Comorbid and concomitant diseases were detected in 297 (48%) of 614 patients. 183 (61.6%) patients had 2 or more diseases in addition to Ps and PsA.
Diseases of the circulatory system were detected in 229 (77.1%) PsA patients with comorbid and concomitant diseases (arterial hypertension – in 194 (65.3%), coronary heart disease – in 22 (7.4%)). Diseases of the endocrine system, metabolic disorders were detected in 156 (52.5%) patients with PsA (diabetes mellitus in 44 (14.8%), hyperlipidemia in 44 (14.8%), metabolic syndrome in 36 (12.1%), obesity in 7 (2.4%), and others). Gastrointestinal diseases were observed in 62 (20.9%) patients. Diseases of the biliary system – in 33 (11.1%) patients. Diseases of the musculoskeletal system and connective tissue that are not associated with PsA – in 44 (14.8%). Diseases of the genitourinary system – in 23 (7.7%) patients. Respiratory diseases – in 17 (5.7%) patients. Infectious diseases – in 11 (3.7%). Eye diseases were detected – in 10 (3.4%) patients. Hematological diseases were diagnosed in 6 (2.0%) patients. Depression – in 4 (1.3%) patients.
Conclusions. Among 297 patients with PsA with comorbid and concomitant diseases, diseases of the circulatory system are the most common (in 77.1%), less often – diseases of the endocrine system, metabolic disorders (in 52.5%) and diseases of the digestive system (in 32%). Uveitis (2.7%), IBD (1.3%), and depression (1.3%) were rarely detected in our cohort. The majority of patients in the Russian registry had mild forms of Ps (61.5%), and severe Ps (BSA>10%) was observed only in 7.8%.
Thus, PsA is associated with a high prevalence of comorbid and concomitant diseases, especially cardiovascular. When choosing a treatment, these diseases should be taken into account. In connection with the new possibilities of therapy, it is necessary to evaluate the potential impact of therapy on patients with comorbid and concomitant diseases in real clinical practice.
Aim – to study the relationship between body composition and bone mineral density (BMD) in postmenopausal women with rheumatoid arthritis (RA).
Material and methods. 68 postmenopausal women, median age 59 [54; 63] years, with RA were included in the study. Bone mineral density (BMD) and body composition were assessed with dual energy X-ray absorptiometry.
Results. 33 (48.5%) women had osteopenia, and 17 (25.0%) – osteoporosis (OP). Low lean muscle mass was found in 10 (14.7%) patients. There were positive correlations between different areal BMD and body weight, trunk fat, trunk lean muscle mass and total lean muscle mass. In the multivariate linear regression analysis total lean muscle mass was associated with BMD of lumbar spine (β=0.638; p=0.001) and total hip (β=0.473; p=0.008), and appendicular lean muscle mass, estimated using the appendicular muscle index, with femoral neck BMD (β=0.360; p=0.014).
Conclusion. 73.5% of patients with RA had a reduced BMD, and 14.7% women – low muscle mass. The revealed significant association between the lean muscle mass and BMD of lumbar spine and proximal femur indicates the importance of detecting and correcting low lean muscle mass, as well as preventing its decline in order to prevent loss of BMD and osteoporotic fractures.
Aims of the trial – to study the frequency of drug use in pregnant women with ankylosing spondylitis (AS), to determine the effect of discontinuation of drugs of various groups, as well as the dose of non-steroidal anti-inflammatory drugs (NSAIDs) used, on AS activity during gestation.
Material and methods. 50 pregnancies in 49 patients with AS that met the modified New York criteria of 1984. The average age of the patients was 31.7±4.9 years, the duration of the disease was 134.4±85.8 months. The visits were conducted at 10–11, 20–21 and 31–32 weeks of gestation. The BASDAI in the month of conception and in the I, II and III trimesters of pregnancy was: 1.4 [0.6; 3.3], 2.3 [1.2; 4.4], 2.8 [1.4; 4.2] and 2.2 [1.6; 4.0], respectively. The total dose of NSAIDs was determined by the NSAID intake index (Dougados M., 2011).
Results and discussion. NSAIDs. After inclusion in the study, the drug of choice was ibuprofen, which was canceled for all women not later than on 32 week of gestation. At the time of conception and in the first, second and third trim. NSAIDs were taken by 23 (46%), 20 (40%), 30 (60%) and 21 (43.8%) women, respectively. NSAIDs intake index in I trimester (5.8 [2.9; 11.8]) was lower than before pregnancy (28.6 [16.7; 50]) and in II (15.5 [4.7; 30.9]) and III trimesters (24.4 [9.5; 50]) (p<0.05). No relationship between the index of ibuprofen intake, as well as the fact of withdrawal of NSAIDs and AS activity throughout gestation was found.
Sulfasalazine (SS) in correspondence with arthritis was taken 3 months before conception by 11 (22%) women, during pregnancy – by 6 (12%) women at a dose of 1.25±0.25 g. Withdrawal of SS was not associated with recurrence of arthritis.
Glucocorticoids (GC) at a dose of 7.5±2.5 mg 3 months before pregnancy and in the I, II and III trimesters of pregnancy were taken by 1 (2%), 4 (8%), 8 (16%) and 10 (20.8%) women, of whom 1 patient had arthritis and 1 had inflammatory bowel disease. The rest of the patients received GC due to high AS activity due to axial manifestations and the unavailability of TNFα inhibitors. Against the background of taking GC, the AS activity did not decrease: BASDAI in the II and III trimesters was 5.5±0.6 and 5.8±1.3 (p>0.05).
TNFα inhibitors: 3 months before pregnancy and in the trim. of pregnancy were taken by 11 (22%), 7 (14%), 6 (12%) and 2 (4.2%) patients. In those who canceled therapy (both independently and on the recommendation of a rheumatologist) on the eve of pregnancy, an increase in AS activity was noted; BASDAI in the month of conception and in I, II, III trimesters was: 2.7 [0.8; 3.5], 5.1 [3.1; 5.9], 5.5 [5; 6] and 6.7 [5.3; 7.3] (p<0.05) compared to the month of conception. Cancellation of TNF-α in the month of conception was a risk factor for high AS activity (BASDAI>4) in the II trimester (OR=30.4; 95% CI: 1.5–612.3; p=0.03) and in the III trimester (OR=32.7; 95% CI: 1.6–662.2; p=0.02).
Conclusion. NSAIDs and GC in low doses do not reduce the activity of AS. Withdrawal of TNF-α inhibitors on the eve of pregnancy is a predictor of high AS activity. It is necessary to increase the knowledge of rheumatologists and patients about the therapeutic possibilities during pregnancy to avoid unjustified drug withdrawal.
Background. EULAR experts include osteoscintigraphy of joints in the list of promising methods for the diagnosis of joint diseases. However, the method remains little used in rheumatology in our country.
Aim of the study – to develop an algorithm for differential diagnosis for the most common arthropathies based on quantitative osteoscintigraphy.
Materials and methods. 3 hours after the injection of pyrophosphate labeled with Tc-99m, scintigraphy of skeletal bones was performed according to the “whole body” program. The joint/adjacent bone uptake ratio was calculated. The CHAID algorithm was used for classification tree constructing.
Results. The study included 266 patients aged 46.6±14.3 years, 134 men (50.4%). Axial spondyloarthritis (including ankylosing spondylitis) was diagnosed in 40 patients, peripheral spondyloarthritis (including reactive arthritis) – in 87, rheumatoid arthritis– in 45, osteoarthritis – in 68, psoriatic arthritis – in 26 people. A total of 2279 joints were included in the analysis. A classification tree algorithm for differential diagnosis of arthropathies was constructed. Key indicators for identifying subgroups in the algorithm were the intensity of radiopharmaceutical uptake in the wrist, knee and hip joints. The significance level of differences between the resulting groups at all points of the algorithm branching, taking into account the Bonferroni adjustment, was p=0.001 or less. In the training sample, 51.5% of the observations were correctly classified. According to results of the cross-validation, the expected rate of correct classifications in the actual application of the algorithm is 38.0%.
Conclusions. An algorithm for differential diagnosis of the most common inflammatory diseases of the joints has been developed. It allows the use of quantitative osteoscintigraphy data in the diagnosis of arthritis.
REVIEWS AND LECTURES
25 years ago, a new non-steroidal anti-inflammatory drug (NSAID) – meloxicam (Movalis®) – entered the clinical practice of our country. This drug was the first embodiment of the concept of selective blockade of cyclooxygenase 2 – the main pathway followed by pharmacological science to create a safe NSAID. A series of large-scale, well-organized randomized controlled trials and observational post-registration studies have confirmed the good efficacy and low incidence of adverse reactions (ADR) when using meloxicam. In our country, this drug has become one of the most popular analgesics. Until now, the original meloxicam has enjoyed a high level of trust among Russian doctors and patients. The reason for this is a long and very extensive experience in the clinical use of meloxicam (over 25 years, 63.7 million packages of the original drug were sold, which means that millions of our Russian citizens were treated with it), as well as a large number of clinical studies conducted by Russian scientists. So, to date, there are 36 Russian studies (n=8498) assessing the efficacy and safety of the original meloxicam in a variety of diseases and clinical conditions. Practically all of these studies have shown good therapeutic results: on average, pain relief is 50–75% of the initial level; good or excellent assessment of the drug effect in 70–80% of patients. The incidence of HP was on average 10.5±5.4%, and there were no serious life-threatening complications.
This review briefly presents the data of Russian and major foreign clinical studies, which studied the therapeutic potential and safety of meloxicam.
The article presents data on epidemiology, pathogenesis, clinical manifestations, diagnosis and therapy of enthesopathy in spondyloarthritis. The approaches to assessment of this pathology are examined and detailed, modern clinical and ultrasound indices are given. The features of enthesopathy in diseases that included in the group of spondyloarthridies are described.
PEDIATRIC RHEUMATOLOGY
The aim of this study was to analyze the clinical, laboratory and molecular genetic data of 26 patients (15 boys, 11 girls) diagnosed with mevalonate kinase deficiency syndrome (MKD).
Subjects and methods. The age of MKD manifestation ranged from 0 to 30.0 months (M – 1.5 months). Clinical manifestations and their severity were extremely diverse: from symptoms resembling Marshall’s syndrome to severe systemic manifestations with respiratory failure, hepatosplenomegaly and pancytopenia.
Results/Conclusion. All patients had homozygous/compound-heterozygous mutations in the MVK gene, including 10 newly described variants. In all 20 patients, who have been treated with IL-1 inhibitors long enough to assess the effect of the treatment, drastic improvement of the condition was noted, but only in 17/20 patients achieved full remission.
Background. Patients with juvenile idiopathic arthritis (JIA) may have incomplete vaccination againts different vaccines leads to lower protective levels of anti-vaccine antibodies.
The aim of the study – to evaluate the rate and the main factors of incomplete vaccination against measels, parotitis, rubella (MMR), and diphtheria in JIA patients.
Methods. In the present study were included data 170 JIA (55 boys and 115 girls) aged from 2 to 17 years, who received scheduled vaccination before the age of 2 years and before JIA onset against measles, parotitis, diphtheria and rubella. Incomplete vaccination means the reduced number of vaccine to age. In all patients the IgG anti-vaccine antibodies levels were detected with ELISA. Data presented with odds ratio ()OR) with 95 confidence interval (CI).
Results. Incomplete vaccination against MMR was in 50 (32.5%) of children less than 6 years. Incomplete vaccination against diphtheria was in 6/16 (37.5%) of children less than 6 year, in 53/110 (48.2%) of children aged 6–14 years and in 26/44 (59.1%) of the JIA patients more than 14 years. The main predictors in logistic regression for incomplete vaccination for MMR were: onset age <4 years (OR=12.2 [95% CI: 5.0–28.9]; p=0.0000001), JIA duration >3.1 years (OR=4.4 [95% CI: 2.0–9.9]; p=0.0002), methotrexate duration >3 years (OR=5.7 [95% CI 2.7–12.0]; p=0.0000012); biologic treatment (OR=2.5 [95% CI: 1.3–4.9]; p=0.008) and treatment >1 biologic (OR=3.3 [95% CI: 1.1–10.4]; p=0.002); for diphtheria were: JIA duration >3.1 years (OR=3.4 [95% CI: 1.8–6.5]; p=0.0002), methotrexate duration >2.8 years (OR=4.1 [95% CI: 2.1–8.1]; p=0.00004), biologic treatment (OR=2.4 [95% CI: 1.3–4.4]; p=0.006). In the multiple regression only JIA onset age (p=0.00001) and duration of methotrexate (p=0.003) were predictors of incomplete vaccination against MMR. Methotrexate duration (p=0.005) and biologics treatment (p=0.05) were predictors of incomplete vaccination against diphtheria.
Conclusion. The main predictor of incomplete vaccination was younger onset age of JIA. Children received more intensive immunosupression usually have scheduled vaccination rarely which leads to increased number of patients without protective antibody levels. These facts indicate the attitude of physicians parents to vaccination in immunocompromised children. Further investigations required for assessment of safety of vaccinations in children with rheumatic diseases may be a factor for changing this prejudice.
ORTHOPEDIC RHEUMATOLOGY AND REHABILITATION
Aim of the research – to evaluate the effectiveness, to analyze the complications and long-term results of total hip arthroplasty (THA) in patients with active psoriatic arthritis (PsA).
Materials and methods. The results of THA were studied in 26 patients with PsA (19 men, 7 women; average age 54.8±3.1 years, from 38 to 56 years) up to 2 years after surgery. The diagnosis of PsA was established according to CASPAR criteria.
Results. The visual analogue scale assessment showed a significant decrease in the intensity of pain in the hip joint in the postoperative period. The average DAPSA activity index before surgery was 25.9 (11–34), after 2 months – 31.3 (16–38), after 6 months – 30.5 (12–37), with a further decrease to 26.1 (12–35) by 24th month. The results of clinical and functional assessment according to Harris in 19 (73%) patients corresponded to an excellent level, in 7 (27%) – to a good level. No infectious, thromboembolic complications were detected. In 1 (4%) patient periprosthetic intraoperative fracture of the femur was diagnosed No new skin psoriatic elements in the field of surgical intervention was fixed.
Conclusion. Our data indicate the effectiveness of THA in active PsA, provided that the requirements for careful planning of the intervention, prevention of possible complications and an individualized approach to rehabilitation are met.
Aim of the study – to determine the risk factors for the early development of osteonecrosis and to analyze the results of surgical treatment of patients with systemic lupus erythematosus in the long term after total hip arthroplasty.
Materials and methods. The study group included 42 patients with systemic lupus erythematosus (SLE) complicated by osteonecrosis (ON) of the femoral head, who underwent 59 total hip arthroplasty (THA) operations. Before surgery and 6–21 years after THA, in order to assess the long-term results of surgical treatment of patients, the following was assessed: activity of the underlying disease – according to the SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index 2000); the severity of irreversible changes in internal organs – according to the SLICC/ACR index of damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology); the clinical and functional state of the hip joint – according to the HHS (Harris Hip Score); the intensity of pain syndrome – according to the visual analogue scale (VAS); quality of life (QOL) – using the SF-36 questionnaire. The concentration of antibodies to cardiolipin (aCL) of IgM and IgG isotypes was determined by enzyme-linked immunosorbent assay (normal range – 0.0–10.0 GPL for IgM, 0–7 MPL for IgG).
Results. After 6–21 years of follow-up after THA, there was a statistically significant decrease in pain intensity according to VAS, improvement according to the HHS from 40.0±14.9 to 83.3±17.4 points, SLE activity according to the SLEDAI-2K from 0 to 20 points (median – 4 [4; 8] points) before surgery and from 0 to 41 points (median – 0 [0; 4] points) after a long period of observation. There was a pronounced statistically significant positive dynamics for all QOL indicators studied (p≤0.005 in all cases). The most significant changes were found on the scales RE (Role-Emotional), RP (Role-Physical Functioning) and BP (Bodily Pain). The early development of ON was associated with the degree of activity of the underlying disease, the cumulative dose of glucocorticoids, kidney damage and arthritis in the first year from the onset of SLE, as well as hematological disorders and the presence of aCL in the blood serum 3 years before the onset of ON. The total number of complications was 10.2%.
Conclusion. Total hip arthroplasty in patients with systemic lupus erythematosus can achieve a statistically significant reduction in pain intensity, increase functional activity and improve their quality of life.
CLINICAL OBSERVATIONS
The present report illustrates efficacy of rituximab (RTX) in granulomatosis with polyangiitis (GPA) with severe lung involvement. Female patient, 45 years old, was ill since March 2016, her disease manifested at the onset with fever, recurrent epistaxis, otitis media, mastoiditis, conjunctivitis and arthritis. Thoracic CT scan showed multiple decaying pulmonary infiltrates. The presence of PR3-ANCA confirmed the diagnosis of GPA. Induction therapy included high doses of glucocorticoids, cyclophosphamide (total dose 4 g), with following azathioprine and mycophenolate mofetil. Lung disease continued to progress with emerging extensive infiltrates and forming a giant cavity with air-fluid level in the right lung. Further treatment included antibiotics followed by surgical draining of lung cavity in December 2018. Fever, necrotic rhinitis and otitis persisted despite treatment, lab findings included red blood cells in the urine, C-reactive protein 90 g/l, thrombocytosis 740×109 /l, anemia (Hb 80 g/l). RTX 2 g and intravenous immunoglobulin were initiated in December 2018, a second course of RTX (0.5 g) was administered 4 months later. Patient’s condition was gradually improving, CT scan at 6 months after RTX treatment showed fibrous tissue in the area of former cavity. One year later, total RTX dose was 3.5 g, further regression of changes and GPA remission were achieved. There were no adverse reactions.
Anti-B cell therapy with RTX is a safe and highly effective option in GPA patients with severe destructive lung disease, potentially curative even in cases of giant pulmonary cavities.
ISSN 1995-4492 (Online)