FRONTIERS
Systemic lupus erythematosus (SLE) is a systemic autoimmune rheumatic disease of unknown etiology, characterized by overproduction of organ-specific autoantibodies to various components of the cell nucleus and the development of immune-inflammatory damage to internal organs. According to modern concepts, one of the key mechanisms of SLE immunopathogenesis is associated with dysregulation of type I interferon (IFN) synthesis The complex of data obtained in the process of fundamental and clinical research served as the basis for the development of a new approach to the pharmacotherapy of SLE, associated with the use of monoclonal antibodies (mAbs) that block the activity of IFN type I or its receptors. Among these drugs, anifrolumab (AFM) occupies a special place, which is a human IgG1 mAbs that bind to cellular receptors for IFN-α. The article discusses the materials of the main studies concerning the efficacy and safety of AFM in SLE, and the prospects for the use of this drug in the treatment of this disease.
INTERNATIONAL AND RUSSIAN GUIDELINES FOR THE TREATMENT OF RHEUMATIC DISEASES
Lyme disease (LD) or tick-borne borreliosis affects thousands of people every year in different regions of the world, primarily the United States and Europe. In endemic areas, early LD is a common disease that requires high medical vigilance. Considering the extreme relevance of this problem for public health, in November 2020, the committee of experts of three American scientific societies published an updated version of the clinical guidelines for the prevention, diagnosis and treatment of LD, the main provisions of which are presented in this article. It is emphasized that in the absence of vaccines, the risk of LD and other diseases transmitted by ticks can be reduced by using personal protective equipment and repellents. Antibiotic prophylaxis is carried out by a single oral administration of doxycycline. In the laboratory diagnosis of LD, the determination of antibodies to B. burgdorfery in the blood serum is a first-line study. At the second stage, serum samples are examined using an immunoblot for IgM and IgG. The basis of treatment of LD is rational antibiotic therapy. The choice of an antibiotic depends on a number of factors, including the presence of extracutaneous manifestations of LD (neuroborreliosis, carditis, arthritis). The most commonly used are doxycycline, amoxicillin, cefuroxime-axetil and ceftriaxone.
ORIGINAL RESEARCH
Aim of the work – to compare the frequency of upper respiratory tract (URT) involvement in patients with ANCAassociated vasculitides (AAV), to reveal its main clinical and radiological patterns and to estimate their association with the serological profile (ANCA presence and type).
Material and methods. This retrospective study evaluated 369 patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). The enrolled patients were diagnosed with AAV according to the ACR criteria, CHCC classification (2012) and EMA algorithm. Patients with URT manifestations underwent standard ENT assessment and X-ray/CT. Serum ANCA levels were measured by ELISA.
Results. URT involvement was diagnosed in 280 (75.9%) patients with AAV. It was significantly more common among
the patients with GPA (86.4%) and EGPA (85.5%) compared with the MPA group (29.2%) (p<0.001).
URT manifestations mainly appeared as sinusitis (77.2% – GPA; 33.3% – MPA; 70.8% – EGPA) and rhinitis with crusting (87.8%, 72.2% and 16.9% respectively).
Proteinase 3 ANCA positive patients had a significantly higher incidence of bone destructive URT lesions, including sinuses wall destruction (p<0.001) and saddle nose deformity (p=0.016), compared with myeloperoxidase-ANCA-positive patients. Similar results were obtained in the GPA group separately.
Localized disease with isolated URT involvement was observed in 41.3% cases of ANCA negative GPA (p<0.001).
Conclusion. The frequency and patterns of upper respiratory tract manifestations depend both on the nosologic form of AAV and type of ANCA. Localized forms of URT involvement can be observed in patients with GPA and are closely associated with absence of ANCA, which determines the need for especially high suspicion level.
Objective of the study – to compare, in real clinical practice, according to the data of the Russian Psoriatic Arthritis Registry, characteristics of two groups of psoriatic arthritis (PsA) patients: with and without nail psoriasis.
Material and methods. 588 PsA patients (277 males and 311 females) with PsA according to CASPAR criteria were included in the Russian Psoriatic Arthritis Registry. Patients’ age was 48.6±0.5 years, disease duration – 7.0±0.3 years. Patients underwent standard clinical examination of PsA activity. Disease activity measures evaluated in this study included DAPSA (Disease Activity in Psoriatic Arthritis), BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and ASDAS-СRP (Ankylosing Spondylitis Disease Activity Score). Enthesitis was measured using LEI (Leeds Enthesitis Index) index. Dactylitis was detected, the number of digits with acute dactylitis was defined. Skin lesion severity was evaluated in terms of BSA (Body Surface Area) affected, and PASI (Psoriasis Area Severity Index); PASI was calculated in case BSA > 3%. The criteria of minimal disease activity (MDA) had been used to assess the treatment efficiency. MDA was achieved if a patient met ≥5 of the 7 following categories: tender joint count (TJC) ≤1, swollen joint count (SJC) ≤1, PASI≤1 or BSA≤3%, patient pain VAS ≤15, patient global activity (PGA) VAS ≤20, Health Assessment Questionnaire Disability Index (HAQ) ≤0.5, and tender entheseal points ≤1. Patients were split into two groups: those with nail psoriasis (group 1), and those without nail psoriasis (group 2).
Results. 312 (53.1%) patients had nail psoriasis and 276 (46.9%) did not. Patients’ age in group 1 was 45.7±11.9 years, in group 2 – 48.8±13.2 years (р>0.05). PsA duration in groups 1 and 2 did not differ, it was 7.1±6.6 and 7.0±6.2 years respectively (р>0.05). Higher proportions of patients with nail psoriasis were male, disabled from working and chronic smokers compared to patients without nail psoriasis: 51.9% vs 44.1% (р=0.013), 37.20% vs 26.40% (р<0.01) and 18.9% vs 8.7% (р<0.01) respectively. Patients with nail psoriasis had more severe erosive peripheral arthritis compared to patients without nail psoriasis. Median TJC was 8 [4–15] vs 5 [2–12] (р=0.002), SJC – 5 [1–9] vs 2 [0–7] (р=0.003), and erosive radiographic arthritis of feet was found in 45.0% vs 31.2% of patients (р=0.003) respectively. Group 1 patients had higher disease activity measured by DAPSA – 25 [15–39] vs 20 [12–33] (p=0.001) and ASDAS-CRP – 3.1 [2.2–4.0] vs 2.8 [1.8–3.5] (р=0.004), compared to group 2 patients. Patients with nail psoriasis had higher frequency of heel enthesitis and dactylitis; axial disease was diagnosed more often among them, compared to patients without nail psoriasis. Heel enthesitis was detected in 53 (17.0%) vs 28 (10.1%; р=0.016), dactylitis – in 76 (24.4%) vs 46 (16.7%; р=0.022), spondylitis – in 109 (35.0%) vs 73 (26.4%; р=0.025) patients respectively. Patients in group 1 had worse skin psoriasis than in group 2. Patients with nail psoriasis significantly more often had moderate and severe skin psoriasis according to BSA, compared to patients without nail psoriasis (39.9% vs 26.1% and 14.8 vs 1.1% respectively; р<0.01 for both comparisons); group 2 patients significantly more often had limited skin psoriasis compared to group 1 patients – in 72.8% vs 45.3% of cases respectively (р<0.01). Median PASI index in groups 1 and 2 was 6 [2–14] vs 3 [1–6] respectively (р<0.01). Group 1 patients gave worse assessment of their disease than group 2 patients; median PGA was 50 [40–70] mm vs 50 [30–65] mm VAS respectively (р=0.044). Less patients with nail psoriasis compared to patients without nail psoriasis had achieved MDA throughout the whole study. At the first visit MDA was detected in 3% vs 9% (р=0.006) of patients, at the second – in 12% vs 27% (р<0.001), at the third – in 14% vs 28% (р=0.011), at the fourth – in 17% vs 38% (р<0.001) and at the fifth in 27% vs 52% (р=0.004) of patients respectively. Patients with and without nail psoriasis were given equivalent therapy with diseasemodifying antirheumatic drugs (DMARDs) and biological agents (bDMARDs). DMARDs were given to 78.2% and 80.1% of patients respectively (р>0.05), it was mostly methotrexate (MTX); MTX was used in 66.0% and 64.1% of cases respectively (р>0.05). bDMARDs were prescribed to 22.1% and 28.3% (р>0.05) of patients, including tumour necrosis factor (TNF) inhibitors – in 67% and 63% of cases, interleukin (IL) inhibitors – in 33% and 37% of cases (р>0.05 for both comparisons). Taking into account the similar disease duration and equivalent therapy in both groups, it could be concluded that patients with nail psoriasis achieved MDA less frequently due to greater disease severity.
Conclusion. Nail involvement is identified in more than half (53%) of PsA patients of the Russian Psoriatic Arthritis Registry. Nail psoriasis is associated with significantly worse disease status as measured by severe peripheral arthritis, enthesitis, dactylitis, spondylitis and skin lesions; higher frequency of erosive arthritis was detected in this category of patients. Patients with nail psoriasis had achieved MDA less frequently compared to patients without nail psoriasis. Nail involvement is associated with worse response to therapy and patients’ disability. These data emphasize the importance of accurate diagnostics of nail psoriasis and optimization of treatment approach, including “targeted” therapy.
Upadacitinib (UPA), a JAK inhibitor, is a new therapeutic option that allows patients with insufficient response to therapy with basic anti-inflammatory drugs (DMARDs) or genetically engineered biological drugs (GEBDs) to achieve the goals of therapy for rheumatoid arthritis (RA). Despite the availability of convincing data from international randomized clinical trials, there is insufficient information about the efficacy and safety profile of UPA, the quality of life of patients receiving the drug in real clinical practice.
Aim of the study – to assess the efficacy and tolerability of the UPA drug at a dose of 15 mg/day in patients with rheumatoid arthritis with moderate and high disease activity and to assess their quality of life in real clinical practice.
Materials and methods. The study included 41 patients with RA with insufficient effect of previous therapy with DMARDs or GEBDs, persisting moderate or high disease activity, who were initiated with UPA therapy in 7 rheumatological centers of the Russian Federation. To assess the activity of the disease, standard indices were used: DAS28- ESR, DAS28-CRP, SDAI, CDAI. Functional ability was assessed according to the HAQ questionnaire, quality of life – according to the EQ-5D questionnaire, the activity of the disease according to the patient’s opinion – according to the RAPID-3 index. The HADS scale was used to identify the states of depression, anxiety and emotional disorder.
Results. During the first week of taking the drug, there was a marked decrease in pain from 60 to 30 mm on a visual analogue scale, which lasted until the third month of therapy. There was a statistically significant decrease in morning stiffness, the number of painful and swollen joints, health assessments by the doctor and patient, erythrocyte sedimentation rate and C-reactive protein (p≤0.001). A decrease in disease activity was also noted according to the dynamics of the activity indices DAS28, SDAI, CDAI (p<0.001). The goals of therapy (remission or low disease activity) by the 3rd month of therapy according to the combined indices of activity DAS28-ESR and DAS28-CRP reached 44.8 and 63.4% of patients, respectively, according to the SDAI index – 56.7%, according to the CDAI index – 25.9%. A pronounced improvement in joint function (70% improvement according to the criteria of the American College of Rheumatology) was noted by 33.3% of patients, population indicators of functional state (HAQ≤0.5) had 15.8% of patients. The difference in the HAQ index by the 3rd month of therapy compared to the indicator before treatment was –0.60 points. The quality of life, assessed by patients using the EQ-5D questionnaire, improved in 98.5% of patients, with a 70% improvement noted in more than a third of them (41.7%). The drug was well tolerated, no adverse reactions were registered by the 3rd month of therapy, all patients continued treatment.
Conclusions. The first results of the use of UPA in RA patients with insufficient efficacy of previous therapy with DMARDs or GEBDs in real clinical practice indicate its efficacy and safety, an improvement in the functional state and quality of life of patients by the 12th week of the study.
Postoperative pain (POP) is a serious complication that reduces the result of total knee (TKA) or hip arthroplasty (THA) in patients with osteoarthritis (OA). The search for predictors of postoperative pain is an actual problem.
The aim of the study – to assessing relationship the polymorphisms of the KCNS1, COMT and OPRM1 genes and the development of POP in OA patients who underwent TKA or THA.
Material and methods. The study group consisted of 95 patients with OA knee or hip (64.6% of women, 65.4±9.0 years) who underwent TKA (47.8%) or THA (52.2%). The presence of POP was determined when pain in the area of surgical intervention ≥40 mm (100 mm visual analog scale, VAS) persisted or appeared 3 and 6 months after surgery. All patients underwent genotyping of polymorphisms of the genes KCNS1 (rs734784), COMT (rs6269, rs4633) and OPRM1 (rs1799971) by polymerase chain reaction in real time using original sequence-specific primers and samples labeled with various fluorescent labels. Registration and interpretation of the obtained results were carried out on the DT-96 amplifier (DNA-Technology LLC, Russia).
Results. POP was observed in 32.6% of patients who underwent TKA or THA. The frequency of POP after TKA and THA was 30.2% and 34.0% (p=0.882). Statistical analysis revealed no differences in the frequencies of the genotypes of the studied genes (p>0,05). The presence of a homozygous genotype of the GG polymorphism of the KCNS1 gene (rs734784) was associated with the presence of POP in accordance with the recessive genetic model (GG vs AA+AG; odds ratio (OR) – 3.96 [95% confidence interval (CI): 1.51; 10.37]; p=0.005). The presence of the mutant allele T (TT+CT) in the genotype of the COMT polymorphism (rs4633) reduced the risk of POP compared to the carrier of the CC genotype (OR=0.32 [95% CI: 0.12; 0.83]; p=0.02) in accordance with the dominant genetic model. There was no significant correlation between the development of POP and the carrier of different genotypes and alleles of the COMT (rs6269) and OPRM1 (rs1799971) genes.
Conclusions. There is a statistically significant association the polymorphism of the KCNS1 (rs734784) and COMT (rs4633) genes and the development of chronic POP in patients who underwent TKA or THA. Further studies of the genetic predisposition to POP are required on more clinical material.
To improve the rheumatology service in the Russian Federation, it is necessary to determine the true extent of primary and general incidence of osteoarthritis (OA).
The aim of the study is a detailed assessment of trends in the dynamics of OA incidence in the Russian Federation, the North-Western Federal district (NWFD) and the Arkhangelsk region (AR).
Materials and methods. We evaluated trends in the dynamics of both incidence and prevalence of OA in the Russian Federation (RF), NWFD and AR in the period 1994–2018 based on data from the annual statistical reports of the Ministry of health of the Russian Federation (form 12). Data on the population of AR were obtained in the regional Bureau of statistics – Archangelskstat, for the northwestern Federal district and the Russian Federation from freely available statistical collections of Rosstat. We analyzed the indicators of the adult population (over 18 years old). To evaluate time trends, we used segmented analysis using the Joinpoint Regression Program (National Cancer Institute, USA) to analyze linear trends, evaluate their statistical significance, and identify time points of their change (joinpoints).
Results. In the period from 2004 to 2012 in Russia was a decline in the number of annually detected cases of OA, the prevalence of OA increased steadily in the 2016 year recorded a decline in the number of cases of OA in NWFD and AR. The analysis showed a discrepancy in the trends of incidence of OA in the Russian Federation, the northwestern Federal district and AR, which was nonlinear and chaotic. In all territories, the prevalence was increasing. In the Russian Federation, the period from 2004 to 2008, when the primary incidence of OA fell sharply, was marked by a stable increase in the prevalence from 2041.6 to 3383.3 per 100 thousand population.
Conclusion. Analysis of official statistical information on the both incidence and prevalence of OA shows a significant variation in indicators, their fluctuations are not related to changes in the practice of diagnosis and treatment of this disease and, most likely, are associated with gaps in its accounting. Improving the epidemiological assessment of OA is possible with the introduction of a system of personalized patient registration-the osteoarthritis registry.
Aim of the research – to determine the frequency of osteoporosis (OP) and to identify risk factors for a decrease in bone mineral density (BMD) in postmenopausal women with systemic sclerosis (SSс).
Subjects and methods. The study included 113 postmenopausal women (median age – 60.0 [54.0; 63.0] years) with a reliable diagnosis of SSc according to the ACR/EULAR criteria (2013). The exclusion criterion was the presence of overlap syndromes. All women were interviewed according to a unified questionnaire, a laboratory and instrumental examination was conducted, including Dual-energy X-ray absorptiometry.
Results. OP and osteopenia in at least one measurement area were diagnosed in 45.1% and 48.7% of women, respectively. Multivariate linear regression analysis revealed a negative effect of the total experience of taking glucocorticoids (GCs) on the value of BMD in the lumbar spine (b=–0.005; R2=0.136; p=0.017). Body mass index (BMI) (b=0.007; R2=0.208; p<0.001), glomerular filtration rate (GFR) (b=0.313; R2=0.213; p<0.001) is positive, and the cumulative dose of GCs (b=–0.269; R2=0.134; p<0.001), the duration of taking proton pump inhibitors (PPI) (b=–0.277; R2=0.291; p<0.001) and the duration of postmenopause (b=–0,223; R2=0.134; p<0.001) negatively affected the BMD of the femoral neck. BMD in the total hip (TH) was generally positively associated with BMI (b=0.493; R2=0.244; p<0.001), GFR (b=0.313; R2=0.150; p<0.001), 25-hydroxy calciferol level (b=0.273; R2=0.284; p=0.001), and negatively – with the cumulative dose of GCs (b=–0.219; R2=0.289; p<0.001).
Conclusion. 93.8% of postmenopausal women with SSс had reduced BMD. Of the traditional risk factors, only BMI, the duration of postmenopause and the level of vitamin D had an impact on the state of BMD, and among the specific ones – the cumulative dose and duration of taking GCs, PPI and GFR.
REVIEWS AND LECTURES
Gout is the most common inflammatory arthritis in adults and has continued to increase in prevalence over the past decades. Gout is characterized by hyperuricemia with the obligatory crystallization of urates and an associated inflammatory reaction, as well as metabolic effects caused, among other things, by these processes. In particular, the diagnosis of gout is identified with a high risk of carbohydrate metabolism disorders, which is 2 times higher than the population risk: according to various sources, from 21 to 26% of patients with gout have type 2 diabetes mellitus (DM 2). However, the role of uric acid and urate-lowering drugs in its development in patients with gout remains controversial. The possibility of influencing the risk of developing diabetes mellitus type 2 of chronic inflammation, the activity of interleukin-1β and other pro-inflammatory cytokines, hyperuricemia, xanthioxidase and other factors associated with gout is discussed. It is possible that the level of uric acid is associated with diabetes and other metabolic diseases, causing pathophysiological changes not only through inflammation, but also oxidative stress, damage to the vascular endothelium. It is also suggested that gout and DM 2 may share genetic markers. The interrelation of violations of purine and carbohydrate metabolism prompts the search for drugs that have a simultaneous positive effect on purine and carbohydrate metabolism. However, it is not clear what the level of uric acid should be considered as a risk factor, there are conflicting data on the possibility of reducing the risk of developing diabetes with various anti-gout therapies.
The article summarizes the modern concepts of microscopic polyangiitis (MPA), a primary ANCA-associated systemic necrotizing vasculitis without immune globulin deposition (pauci-immune) that affects mainly small vessels, while granulomatous inflammation is absent. Necrotizing glomerulonephritis is very common and pulmonary capillaritis often occurs. MPA can cause rapidly progressive damage to organ systems. The modern possibilities of MPA treatment, primarily anti-B cell therapy with rituximab, are discussed.
ORTHOPEDIC RHEUMATOLOGY AND REHABILITATION
Objective – to compare the results and complications of open wedge high tibial osteotomy (OWHTO) in patients operated on according to the standard technique and using the developed method of performing the operation using the original fixator.
Materials and methods. 73 patients with primary and secondary OA of the knee I–III stages were recruited into the study, which were divided into 2 groups. Group 1 consisted of 43 patients, who underwent 46 OWHTO from 2005 to 2019 using the standard technique using short plates with a fixed spacer (Puddu I (5 times) and II generation (24 times), Osteomed (17 times)) and bone grafting. Group 2 consisted of 30 patients who were operated on in 2018– 2020 using the developed surgical technique and the original fixator. To assess the result, we studied the change in pain according to the Visual Analog Scale (VAS), as well as the functional (FS) and objective scores (OS) of the knee according to the Knee Society Score (KSS) before surgery, after 3 months and 1 year after OWHTO.
Results. In group 1, one year after OWHTO, the results were obtained: excellent in 43.5% of cases, good – in 41.0% and satisfactory – in 15.2% of patients. In group 2, an excellent result was obtained in 59.3% of patients, good – in 33.4% and satisfactory – in 7.3% of cases. In group 1, 15 (32.7%) patients were diagnosed with 26 complications, and in group 2 – 5 (16.6%) patients with 5 complications.
Conclusions. The use of the developed surgical technique and the original fixator made it possible to increase the percentage of excellent and good treatment results from 84.5% to 92.7% and to reduce the number of complications associated with OWHTO from 32.7% to 16.6%.
CLINICAL OBSERVATIONS
Sarcoidosis is a rare multisystem disease which may accompany various autoimmune diseases in 17,6% cases. Despite of the fact that T-cell immunity impairments play a key role in these two conditions, their combination is extremely rare. It is difficult to choose therapy for patients with coexisted diseases, and it is even harder in case of comorbid pathology. In this article we considered a complicated case of treatment patient with a coexistence of rheumatoid arthritis and sarcoidosis, which had occurred during rituximab therapy. In addition to the combination of two autoimmune diseases, the selection of therapy for this patient was complicated by secondary immunodeficiency and intolerance to the main basic drugs.
Alopecia areata (АA) is an autoimmune multifactorial disease characterized by increased hair loss as a result of morphological and functional changes in hair follicles. АA is divided into four main forms, among which the most severe is the universal form (UA), in which complete hair loss is possible throughout the body. Alopecia in the practice of a rheumatologist can occur with some systemic diseases of the connective tissue, with the use of high doses of chemotherapy drugs and, more recently, with the use of inhibitors of tumor necrosis factors alpha (TNF-α). The article presents 3 clinical cases of the development of UA during therapy with TNF-α. Possible mechanisms are discussed, as well as the role of pro-inflammatory cytokines in the development of this condition.
ISSN 1995-4492 (Online)