FRONTIERS
Rheumatoid arthritis (RA) is an immune-mediated rheumatic disease (IMRDs) characterized by chronic erosive arthritis and systemic damage to internal organs, leading to early disability and reduced life expectancy in patients. A particularly important place among the systemic manifestations of RA is occupied by interstitial lung diseases (ILD) – the most severe form of pulmonary pathology in RA, defined as RA-ILD, which is pathogenetically associated with risk factors (smoking, etc.) and autoimmune mechanisms underlying RA. RA-ILD is a subtype of RA characterized by a severe course and a poor prognosis. The review presents new data regarding risk factors and biomarkers for RA-ILD; modern diagnostic capabilities based on the use of functional lung tests, high-resolution computed tomography, ultrasound examination of the lungs. Particular attention is paid to the efficacy and safety of pharmacotherapy, including methotrexate, biologics, JAK inhibitors, and antifibrotic therapy. An algorithm for the pharmacotherapy of RA-ILD has been proposed.
PROBLEMS OF RHEUMATOLOGY DURING THE 2019 CORONAVIRUS PANDEMIC
The SARS-CoV-2 coronavirus pandemic is a leading medical problem that is in the focus of attention of representatives of all medical specialties. In addition to fighting the COVID-19 infection itself, the task of preventing and treating a wide range of complications arising after the disease is becoming increasingly urgent. One of these complications is avascular necrosis (AN) of bone tissue – a severe pathology that leads to serious suffering, a decrease in the quality of life and disability of patients. For the period from 2020 to 2022 there are 9 reviews in the world literature devoted to the pathogenesis, clinical features and treatment possibilities of this complication. During the same period, 5 articles were published describing clinical observations of AN after suffering COVID-19.
The purpose of this work is to demonstrate our own clinical observations, as well as to review the available literature data on the problem of AN after COVID-19 infection. Based on the analysis, it can be concluded that AN after SARS-CoV-2 infection most often develops in the femoral head (>50% of cases), occurs regardless of the severity of the disease and the cumulative dose of glucocorticoids used in the acute period of the disease. It seems advisable to perform an MRI of the hip joints at least once every 3 months for all patients who have had COVID-19 in severe and moderate form during the first year after convalescence.
PROGRESS IN RHEUMATOLOGY IN THE XXI CENTURY
Among the variety of clinical manifestations of psoriatic arthritis (PsA) – including peripheral arthritis, dactylitis, enthesitis, and axial disease – spondylitis is the least studied. There is no generally accepted definition of axial PsA (axPsA), nor is there any common terminology or diagnostic criteria for it. In the rheumatology community, there is also no consensus regarding radiological and MRI assessment of axial involvement in PsA patients, while disease activity indexes and the therapeutic tactics are borrowed from those used in treating axial spondyloarthritis (axSpA) and ankylosing spondylitis (AS). However, despite a range of similarities in immunopathogenetic mechanisms of axPsA and axSpA, there are also certain differences that may affect the treatment response in these patients. The aim of this review is the analysis of data on axial disease in PsA. The article discusses the genetic features, clinical presentations, imaging techniques, differential diagnostics and treatment options of axPsA.
REVIEWS AND LECTURES
Immune-mediated rheumatic diseases (IMRDs) are a broad group of pathological conditions based on impaired immunological tolerance to one’s own tissues leading to inflammation and irreversible organ damage. Laboratory diagnosis of IMRDs includes a wide range of biomarkers (autoantibodies, acute phase proteins, cytokines, markers of endothelial damage, components of the complement system, immunoglobulins, cryoglobulins, lymphocyte subpopulations, indicators of bone metabolism, apoptosis markers, genetic markers, etc). One of the leading aspects of laboratory diagnosis of IMRDs is the study of the level of inflammation markers in the blood (erythrocyte sedimentation rate, C-reactive protein (CRP), serum amyloid protein (CAA), ferritin, procalcitonin, apolipoprotein AI, calprotectin, etc). The analysis of inflammation markers makes it possible to assess the disease activity, the nature of the progression and the prognosis of the outcomes of a chronic inflammatory process, as well as the effectiveness of the therapy. The review presents the latest data on the role of the most frequently studied inflammatory markers such as CRP, CAA and ferritin.
Calcium pyrophosphate crystal deposition disease (CPPD) is a disease caused by the deposition of calcium pyrophosphate crystals, mainly in the articular cartilage, and often manifests as severe acute or chronic arthritis. Therapy given in such cases with non-steroidal anti-inflammatory drugs, colchicine, methotrexate and glucocorticoids is often effective. In these cases, the possibility of prescribing biological drugs, primarily interleukin 1 (IL-1) inhibitors, is being considered. The article analyzes the experience of using Anakinra, an IL-1 receptor antagonist, registered in the Russian Federation in 2021, in 5 patients with persistent arthritis in CPPD. The article also presents an analysis of data from key studies on the use of the drug in patients with CPPD.
Gastrointestinal disorders are important place among the visceral manifestations of systemic autoimmune and immunoinflammatory rheumatic diseases (RD). Pathology of the esophagus, stomach, small and large intestine can vary from moderate functional disorders to the development of severe chronic inflammation with metaplasia and dysplasia of the mucous membrane, the formation of multiple erosions, hemorrhages and deep ulcers. Complications of gastrointestinal pathology in RD, such as bleeding, perforations and strictures, can cause death. This review examines the main clinical manifestations, possibilities of diagnosis and treatment of gastrointestinal lesions in systemic scleroderma, idiopathic inflammatory myopathies, systemic vasculitis, Sjogren’s syndrome and disease, as well as systemic lupus erythematosus.
Patients with rheumatic diseases (RD) are at high risk of osteoporosis (OP) and osteoporotic fractures. The Trabecular bone score (TBS) is a relatively novel method of assessing bone quality, which independently predicts fracture risk regardless of bone mineral density (BMD). A lower TBS in patients with RD compared to controls is shown in most studies concerning TBS and RD. The data obtained indicate that TBS predicts fractures better in RD, especially in patients receiving glucocorticoids, than BMD or the FRAX algorithm. TBS degradation has been associated with disease activity in ankylosing spondylitis, systemic sclerosis, and rheumatoid arthritis in a few studies. However, there is little data in the literature on the effect of rheumatic disease therapy and OP treatment in patients with RD on predictive ability of TBS for incident fracture.
ORIGINAL RESEARCH
Objective – to compare the clinical efficacy and cost-effectiveness of IL-17 inhibitors (SEC, IXE, NTK) in the treatment of adult patients with ankylosing spondylitis (AS) in the healthcare system of the Russian Federation.
Material and methods. The study is a sub-analysis of a previously published systematic review and network meta-analysis of the comparative efficacy of biologics in adult patients with AS in the Russian Federation. NNT values were calculated for BASDAI 50 and ASAS 20/40 after 16 weeks of therapy for all studied drugs. CpR was estimated for each biologic after 16 weeks and one year of therapy. Additionally, we carried out an assessment of the financial burden of the most cost-effective strategies for the treatment of AS.
Results. The use of NTK is characterized by an average of no more than three patients needed to treat to achieve one ASAS 20/40 or BASDAI 50 response, while on IXE and SEC – no more than 4–5 patients need to be treated, depending on the estimated effectiveness criterion. According to CpR estimate, NTK is the most cost-effective IL-17 inhibitor for the treatment of AS, both after 16 weeks and after one year of therapy.
Conclusion. The obtained results make it possible to compare the effectiveness of IL-17 inhibitors from a clinical and economic points of view and can be used both in decision making process of treatment strategies for individual patients, and at the population level – when deciding on the reimbursement of drugs
Objective – to evaluate the features of clinical manifestations, course, outcomes and quality of life related to health in patients with systemic lupus erythematosus in the Republic of Kazakhstan.
Patients and methods. The study included 102 patients with systemic lupus erythematosus (SLE) with a reliable diagnosis according to SLICC (2012). Disease activity was assessed by the SLEDAI 2K index, organ damage (IOD) by SLICC/ACR (2000). Statistical processing was carried out using SPSS 13 software (IBM Corp., USA). Variables with a parametric distribution are presented as М±SD, nonparametric – as a median (Me) [25th; 75th percentile].
Results and discussion. The cohort was dominated by female patients (98%), Asians (83.33%), young patients (33.85±10.58 years) with a disease duration of 5 [2; 9] years with high (30.8%) and very high (39.2%) degree of activity (SLEDAI-2K – 17.64±8.80 points). The debut of the disease was in 18.6% of patients in adolescence, it was characterized by an unfavorable course. Clinical manifestations of the disease: skin lesions (acute active and chronic forms) (98%), joints (79.4%), non-scarring alopecia (75.5%), neuropsychiatric disorders (49%), mucous membranes (46.1%), hematological (54.9%) and immunological disorders (100%). IOD: low – in 20.6%, medium – in 59.8%, high – in 9.8% of patients, 0 – in 9.8%, Risk factors for poor outcome were in 93.1% of patients. Assessment of health-related quality of life (HRQOL) in SLE patients showed a significant decrease on all scales. Correction of the treatment program, taking into account the factors of adverse outcome (FRNI), consisted in strengthening therapy with the inclusion of genetically engineered biological drugs (GEBP).
Conclusion. SLE is a socially significant disease in Kazakhstan with a high incidence rate (101%) over 10 years (2009–2018). The cohort of SLE patients is dominated by young people, females. The duration of the disease is up to 5 years with a delayed verification of the diagnosis of SLE. Organ damage is already in the onset of the disease and the presence of FRNI of the disease in 93.1% of patients, which indicates the severity of the course, which requires early diagnosis and active involvement of pathogenetic treatment, including GEBD.
Purpose of the study – to study the efficacy and safety of tenoxicam (Texared®) in patients with active axial spondyloarthritis.
Material and methods. The study included 35 patients with active axial spondyloarthritis with BASDAI≥4.0. Patients were given continuous oral tenoxicam (Texared®, Dr. Reddy’s Laboratories) at a dosage of 20 mg/day. Subsequently, 5 patients were excluded from the study due to discontinuation of the drug after 5–10 days of administration. 30 patients were included in the final analysis. Initially and after 30 days, to assess the severity of pain and stiffness, activity, patients filled out questionnaires in electronic form using Google forms, a general assessment of pain in the lower back and the intensity of night pain by the patient, subjective sleep characteristics were carried out. The doctor calculated the BASDAI, ASDAS-CRP, BASMI indices, and evaluated the activity according to the doctor’s opinion. The baseline blood pressure level was determined, and a patient diary was issued for ambulatory blood pressure measurement in the morning/evening for 30 days. After 30 days, the patient’s ambulatory blood pressure control was assessed. At baseline and after 30 days, biochemical blood parameters were studied, including a complete blood and urine test.
Results and conclusion. In patients with axial spondyloarthritis with high and very high activity, a positive effect of tenoxicam (Texared®) therapy on disease activity was noted. The effect of Texared® develops with regular use already during the first 2 weeks, and after 4 weeks there is a clear decrease in the severity of pain in the lower back, a decrease in the duration of morning stiffness. The drug is well tolerated, has a favorable safety profile, no serious adverse events and few side effects that do not require discontinuation of therapy.
Background. The goal of “treat-to-target” strategy (T2T) in psoriatic arthritis (PsA) is attaining remission or minimal disease activity (MDA). The benefits of T2T are shown recently in the study TICOPA and REMARCA. But prognostic factors for achievement MDA in PsA patients (pts) at the early-stage hasn’t been studied yet.
Objective – to determine the prognostic factors associated with achievement of minimal disease activity within 12 months (mo) of treatment according to T2T strategy in early psoriatic arthritis patients.
Methods. 77 pts (M/F=36/41) with early PsA fulfilling the CASPAR criteria were included. Mean age 36.9±10.45 years, PsA duration 11.1±10.0 mo, psoriasis duration 82.8±92.1 mo. At baseline (BL) and at 12 mo of therapy PsA activity by tender joins count (TJC) out of 68; swelling joints count (SJC) out of 66; pain; patient global assessment disease activity (PGA) using visual analogue scale; CRP; dactylitis, enthesitis by LEI and plantar fascia; BSA; HAQ and fatigue by FACIT 4 scale were evaluated. A score FACIT <30 indicates severe fatigue, the higher the score – the better the quality of life. All pts were given therapy with Methotrexate (MTX) s/c, 29 pts with ineffectiveness of MTX after 3–9 mo of treatment were added biologic DMARDs. The one-factor model of logistic regression was used to identify a group of features that are associated with achievement MDA.
Results. By 12 mo of therapy, the proportion of pts who have reached MDA (5/7) were calculated. Pts were split into 2 groups: MDA+ (n=45) and MDA– (n=32).Comparative analysis of BL features in both groups and one-factor model of logistic regression showed the following features were associated with achievement MDA: TJC and SJC<3 (p<0.001); PGA≤20 mm (p<0.001); pain≤15 mm (p<0.001); CRP≤5 mg/l (p<0.03); HAQ≤0.5 (p<0.001); FACIT>30 points (p<0.021); absent of entesitis (p<0.003), dactylitis (p<0.029) and nail damage (p<0.012). Early PsA pts with combination of these features on first visit have more chance to achieve MDA in comparison to PsA pts without them (OR=9.684 [95% CI: 4.6–20.4]).
Conclusion. It is a combination of features on first visit – oligoarthritis, moderate activity, absent of entesitis, dactylitis, nail psoriasis, significant impact on function and fatigue – that constitutes a clinical prognostic factors for achievement MDA after 12 mo of treatment in pts with early PsA according T2T.
Background. Recently, numerous studies have shown that TNFAIP3 gene polymorphisms have been associated with susceptibility to certain autoimmune inflammatory diseases, including systemic lupus erythematosus, scleroderma, rheumatoid arthritis and psoriasis. However, the results of studies devoted to the study of associations between TNFAIP3 gene polymorphisms and the risk of ankylosing spondylitis (AS) are ambiguous and few.
The aim of the study was to study the possible association of hs10499194 polymorphism of the TNFAIP3 gene with a predisposition to AS and its clinical phenotypes.
Material and methods. The rs10499194 S/T polymorphism of the TNFA1P3 gene was studied in two hundred patients with AS (130 men and 70 women). All patients were diagnosed with AS, according to the modified New York criteria, 1984 and high activity of the disease. Demographic and clinical-serological characteristics were studied in all patients. The average age of patients was 39.4±12.6 years; the average duration of the disease was 15.0±10.6 years. Out of 200 patients, 175 (87.5%) were seropositive for HLA-B27 antigen. Extra axial arthritis was detected in 125 (62.5%) patients, 148 (74.0%) had enthesitis, 137 (68.5%) had coxitis. The polymorphism rs10499194 of the TNFAIP3 gene was studied using an allelespecific polymerase chain reaction in real time (PCR-RV) using the Synthol kit.
Results. The analysis of the frequencies of genotypes and alleles did not show significant differences with the control group. Stratification by sex, age, and clinical manifestations showed an association of the CT genotype with an increased risk of AS among men (OR=2.24; p=0.010), the TT genotype and the T allele with a high risk of predisposition to the development of extra axillary peripheral arthritis (OR=3.94; p=0.019 and OR=1.64; p=0.027 respectively). The BASDAI index was statistically significantly higher in carriers of the TT genotype compared to the CT genotype (p=0.002).
Conclusion. The present study confirmed the association of the genetic polymorphism rs10499194 of the TNFAIP3 gene with AS. Stratification by gender and clinical manifestations showed an association of the CT genotype with an increased risk of AS among men, the TT genotype and the T allele with a high risk of predisposition to the development of extra axillary peripheral arthritis and a high BASDAI index in carriers of the TT genotype.
CLINICAL OBSERVATION
The study objective is to demonstrate a rare cause of recurrent acute cerebrovascular diseases in a young patient – Sneddon syndrome. The patient revealed gene polymorphism: homozygous 4G/5G in the plasminogen activator inhibitor-1 (PAI-1) gene, C807T in the glycoprotein I gene (GPIa), T1565C in the glycoprotein III gene (GPIIIa), G1639A in the vitamin K epoxide reductase gene (VKORC1), increased homocysteine, which were risk factors for thrombosis.
Articles
ISSN 1995-4492 (Online)