Progression of sacroiliitis in men and women according to the cohort of early axial spondyloarthritis (CORSAR) over 3 years of follow-up

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease with predominant involvement of the sacroiliac joints (SIJ) and/or the spine. Despite the fact that the prevalence of axSpA is almost the same in men and women, there is evidence of a delay in diagnosis and a more severe course of the disease in females. The available reports on the progression of structural changes in the SIJ in men and women with early axSpA are contradictory. Meanwhile, the analysis of radiographic progression in the SIJ has fundamental importance both for timely diagnosis and for assessing the effectiveness of therapy in axSpA. Such studies have not yet been carried out in the Russian Federation.Objective: to assess the radiographic progression of sacroiliitis (SI) over 3 years in men and women with early axSpA.Material and methods. The study included patients from the cohort of early axSpA CORSAR, formed at the V.A. Nasonova Research Institute of Rheumatology. Currently, it includes 175 patients with axSpA. We analyzed the data of 64 patients, followed for at least 3 years. To assess the radiographic progression of the disease at baseline and after 3 years, the sum of X-ray stages of SI in the left and right SIJ was determined (the total stage of SI). Progression was assessed by the change in the total stage of SI in the right and left SIJ (0-8) during the observation period. We also calculated the proportion of patients with deterioration (increase in the total stage of SI by at least 1 stage), with improvement (decrease in the total stage of SI by at least 1 stage) and without progression. In order to fully exclude the error in measuring the radiographic progression of SI, we counted patients with “net” progression, that is, the proportion of patients with improvement was subtracted from the proportion of patients with deterioration.Results. Among 64 patients with early axSpA, there were 37 (57.8%) men and 27 (42.2%) women. For 3 years, the median of the total stage SI in men was 0 [0; 1], in women - 0 [0; 2] (p>0.05). When assessing the progression of the total stage SI over 3 years, no significant differences were found between the number of men and women with improvement, with deterioration, “net” progression and without progression. Men with early axSpA showed a higher level of C-reactive protein (CRP) at baseline, women had higher BASDAI and ASDAS CRP values after 3 years. In 8% of patients, there was a regression of X-ray signs of SI.Conclusion. The radiographic progression of SI in patients with early axSpA does not depend on gender and disease activity. In some patients with early axSpA, reverse development of structural damage to the SIJ is possible.

Dynamics of clinical manifestations and cytokine concentrations in rheumatoid arthritis patients on tofacitinib therapy

Objective - to study the dynamics of clinical and laboratory parameters of inflammatory activity of the disease and cytokines in rheumatoid arthritis (RA) patients on a background of tofacitinib (TOFA) treatment.Material and methods. Ten patients with a reliable diagnosis of RA have been examined: patients' age was 51.0 (48.0; 62.0) years, duration of disease was 7.0 (3.0; 20.0) years. All patients had high disease activity: DAS28 -5.88 (5.53; 5.94), CDAI - 33.0 (29.0; 36.0), SDAI - 33.72 (30.75; 36.85). All patients were treated with TOFA at a dose of 5 mg 2 times a day on a background of methotrexate therapy, non-steroidal anti-inflammatory drugs, and glucocorticoids. Observations were performed before treatment and after 3 and 6 months of therapy. Serum levels of 15 cytokines (IL-1β, IL-4, IL-6, TNF-α, INF-γ, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, sCD40L) were examined using multiplex xMAP technology.After 3 and 6 months of TOFA therapy, there was a significant decrease in DAS28 of 4.55 (3.47; 5.16) and 3.92 (3.80; 4.60); CDAI - 16.5 (11.0; 23.0) and 18.0 (15.0; 19.0); SDAI - 16.6 (11.23; 23.06) and 18.07 (15.06; 19.10); ESR - 19.0 (11.0; 26.0) and 7.0 (4.0; 18.0); CRP - 0.56 (0.50; 1.99) and 0.71 (0.51; 1.1) respectively. IL-6 levels decreased after 3 and 6 months of therapy (p<0.05). The concentration of INF-γ significantly decreased after 3 months (p<0.05), but remained unchanged thereafter. Concentrations of IL-25 and IL-31 decreased after 3 months (p<0.05), and by the 6th month of treatment there was an increase, however, not reaching the initial values.Conclusion. The results of the study show the efficacy of TOFA in RA and create prerequisites for further study of the cytokine-dependent mechanisms of inflammation in this disease.

Urate-lowering drugs in the treatment of gout: The unknown about the known

The main direction of drug therapy for gout and other diseases associated with hyperuricemia is the long-term use of drugs aimed at correcting the level of uric acid. However, in addition to the urate-lowering effect, these drugs may have other beneficial pleiotropic effects. The article will discuss the additional effects of xanthine oxidase inhibitors, as well as drugs used to treat gout-related diseases that have urate-lowering effects.

Anxiety, depression and stress tension screening in patients with rheumatic and musculoskeletal diseases at the onset of the 2019 coronavirus disease (COVID-19) pandemic

The aim - screening of anxiety, depression and stress in patients with rheumatic and musculoskeletal diseases (RMD) and medical workers at the beginning of the COVID-19.Material and methods. 150 patients (men/women: 39 (26.0%)/111 (74.0%); mean age - 43.2±16.1 years) with RMD, hospitalized at the V.A. Nasonova Research Institute of Rheumatology (Moscow) from July to November 2020, and 32 relatively healthy medical workers (men/women: 3 (9.38%)/29 (90.6%), mean age - 40.7±14.6 years) as a control group was included in the study. The Hospital Anxiety and Depression Scale (HADS) and the Depression Anxiety and Stress Scale - 21 Items (DASS-21) were used for anxiety, depression and stress screening. Results. Frequency of anxiety-depressive spectrum disorders in patients with RMD was 48% (according to DASS-21) and 27.2% (according to HADS), which did not differ significantly from the control group - 46.9% and 18.8% respectively. According to the DASS-21, patients with systemic sclerosis were significantly more likely to have a combination of clinically significant anxiety, depression and stress compared to healthy control (6 (46.2%) vs 4 (12.5%); p=0.02) and patients with spondyloarthritis (6 (46.2% vs 5 (16.1%); p=0.045). The severity of anxiety was significantly higher among patients with RMD - systemic lupus erythematosus, primary Sjogren's syndrome and systemic sclerosis, according to both scales. The severity of depression, anxiety and stress was significantly higher in women with RMD, rural residents and patients taking moderate and high doses of glucocorticoids. The pathological stress level was experienced by younger medical workers (27.5±5.45 vs 45.8±13.8 years; p=0.001). The transferred coronavirus infection did not lead to an increase in the severity of depression, anxiety and stress tension among patients, however, among medical workers, the frequency of clinically significant anxiety (4 (57.1%) vs 6 (24%)) and stress (3 (42.8%) vs 5 (20%)) was 2.2-2.9 times higher in those who have been ill. When compared with the results of the similar screening by HADS in 2012, the proportion of RМD-patients with clinically significant anxiety and depression over the past 8 years and in connection with the pandemic COVID-19 has not significantly changed.Conclusion. A new threat to health, isolation and uncertainty at the beginning of the COVID-19 were an additional stressful factor for patients with RМD, however, given the high background prevalence of low-severity chronic depression with frequent onset before RМD, the factor of the COVID-19 is not a key factor in provoking mental disorders.

The effect of late diagnosis on survival and risk of vascular complications in Takayasu's arteritis patients

Aim. To assess the effect of late diagnosis on survival and risk of vascular complications in Takayasu's arteritis (TA) patients. Methods. 183 patients with TA who were treated at the Sverdlovsk Regional Clinical Hospital No. 1 during the period from 01.01.1979 to 31.04.2018 were examined. There were 139 women and 44 men included, median age at the time of diagnosis being 35 [24; 44] years in females and 34 [26.5; 42] years in males and a median interval from the first symptoms onset to the diagnosis of 3 [1; 7] and 4 [1.5; 8] years respectively. The diagnosis of TA met the ACR criteria (1990).Results. During the follow-up period, 31 deaths were observed (18 in males and 13 in females). The median age of death for women was 36 [32-44] years, for men - 50 [40-57] years. Cardiovascular complications were recorded in 72 patients (27 men and 45 women). Vascular complications and namely acute cerebrovascular accident observed in 31 (43%) patients, including ischemic stroke in 24 (35%), transient ischemic attack in 3 (3%) and hemorrhagic stroke in 4 (6%) were the most frequent. Arterial thromboses were registered in 32 (44%) cases. In 162 (88.5%) patients, the diagnosis was established more than six months after the appearance of the first symptoms.At the primary physician visit in 71 (39%) patients, the initial diagnosis was erroneous. The most common symptoms they had were regarded as a manifestation of arterial hypertension (in 18% cases). 4 years or more interval from the onset of TA symptoms to diagnosis was associated with a significant cardiovascular events odds increase (OR=1.8; 95% CI: 1.07-3.34) and premature death by the 5th year of follow-up (OR=2.9; 95% CI: 1,27-6,55).Conclusion. In the retrospective TA cohort setting, late diagnosis verification and delayed treatment initiation were associated with an increased risk of premature death and severe vascular complications, described earlier in other samplings. Timely diagnosis and as early as possible appropriate treatment administration can prevent the disease progression and disabling complications occurrence.

The effect of therapy on subclinical atherosclerosis of the carotid arteries in patients with calcium pyrophosphate crystal deposition disease and osteoarthritis (pilot study)

Endothelial dysfunction associated with chronic microcrystalline inflammation plays a role in the progression of atherosclerosis in calcium pyrophosphate crystal deposition diseases (CPPD).The aim of the study was to assess the dynamics of the development of atherosclerosis based on changes in the thickness of the intima-media complex (ICIM) of the carotid arteries (CA) in patients with CPPD receiving long-term anti-inflammatory therapy (colchicine, methotrexate, hydroxychloroquine).Materials and methods. 26 patients with CPPD and 26 patients with osteoarthritis aged over 18 years old were included. Exclusion criteria: age >65 years; presence of cardiovascular diseases. The blood lipid spectrum, hs-CRP level, anthropometric parameters were determined for all, and Doppler ultrasound ultrasonography of the carotid arteries (CA) was performed. Patients were followed up for not <6 months, assessed ICIM CA at 1 visit, then patients with CPPD, at the discretion of the attending physician, were prescribed methotrexate at a dose of 15 mg per week, hydroxychloroquine 200 mg 1 time per day or colchicine 0.5 mg 2 times a day. Patients could take NSAIDs if they were in pain. The SCORE index has been calculated for everyone.Results. Initially, ICIM values did not differ in patients with CPPD and OA. Initially, ICIM>0.9 mm were detected in 11 of 22 (50%) patients with CPPD and in OA in 8 of 19 (42%) (p=0.39). In dynamics, patients with CPPD revealed a decrease in the number of patients with ICIM>0.9 mm from 42 to 18%. At the same time, in 8 patients with CPPD, ICIM>0.9 mm was combined with a CRP level >0.2 mg/l. Out of 22 patients with CPPD, 14 (64%) patients showed a decrease in the mean values of ICIM, in 2 (9%) patients - an increase, in 5 patients the mean values of ICIM did not change. After 6 months of therapy, out of 11 patients with CPPD with ICIM >0.9 mm, after 6 months of therapy, in 7 cases there was a decrease in the indicator less than the specified value, in 5 of them a decrease in serum CRP level <2 mg/l was recorded. In patients with CPPD, the serum CRP level significantly decreased; in patients with OA, it did not change. Out of 19 patients with OA, 9 (47%) patients showed an increase in the mean ICIM over time, while the rest did not change. In those treated with hydroxychloroquine, a decrease in the mean ICIM parameters was observed in 5 out of 6 (83%) patients, colchicine - in 6 out of 9 (67%) patients, methotrexate - in 4 out of 7 (57%) patients.With CPPD, the result of therapy with colchicine, methotrexate and hydroxychloroquine in relation to the development of the initial signs of atherosclerosis according to Doppler ultrasound ultrasonography of CA can be realized based on the presence of chronic inflammation.

Review of guideline for the management of ANCA-associated vasculitis, presented in 2021 by the American College of Rheumatology/Vasculitis Foundation

The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of severe life-threatening autoimmune diseases, and one of the most important problems in practical rheumatology. This article discusses 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of AAVs, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). The guideline features 26 recommendations and 5 upgraded position statements for GPA/ MPA, as well as 15 recommendations and 5 upgraded position statements for EGPA, which became the basis for the proposed algorithms for the treatment of patients with GPA/MPA and EGPA. Particular attention has been paid to the use of biologics.

Composition of the body in male patients with rheumatoid arthritis with account of androgenic status

Aim. To evaluate alterations in body composition and bone mineral density (BMD) in male patients with rheumatoid arthritis (RA) taking into account their androgen status. Materials and methods. The single-stage study included 96 male RA patients. The mean age of patients was 59 [54; 64.75] years. The control group included 30 healthy men of comparable age. The androgen status assessment was based on sex hormone binding globulin (SHBG), total and free testosterone levels determination. Body composition and BMD measurements were performed using dual-energy X-ray absorptiometry (DXA) on the Stratos dR device (DMS, France) with the program “Whole Body”. Depending on the combination of BMD, lean- and fat-mass parameters, phenotypes of body composition were determined. The study was approved by Pirogov Russian National Research Medical University Local Ethics Committee. All patients signed informed consent.Results. Generally, lumbar spine, femoral neck and total hip BMD in RA patients was significantly less than in the control group (p<0.05). In 69 (71.9%) patients with RA osteopenic syndrome was detected. It was represented by osteopenia and osteoporosis (OP) in 60.4% and 11.5% of cases respectively. The spine and femoral neck BMD correlated negatively with SHBG level, and positive correlation was detected between BMD and free testosterone level. The RA patients had significantly less lean mass than the control group. Low lean mass was found in 48.9% of patients in the main group and was not detected in the control group. Appendicular lean mass (ALM) correlated positively with total and free testosterone levels. According to DXA data, the adipose tissue content (%) corresponded to obesity in 63.3% of patients. Adipose tissue indicators correlated negatively with SHBG, total and free testosterone levels. The BMD of various skeleton parts correlated positively with trunk lean mass, and the femoral neck and total hip BMD had positive relationships with body mass index (BMI). Body composition alterations were revealed in 93.2% of RA patients. The most common phenotypes were osteosarcopenic obesity (25%), osteopenic obesity (21.6%) and osteopenic sarcopenia (14.8%). Conclusion. Our study shows that RA course in men is associated with the development of osteopenic syndrome in 71.9% of cases and ALM decrease to diagnostic values of sarcopenia in 48.9% of cases. This fact should be considered in the development of a gender approach to RA patients management and rehabilitation.

Adult Still's disease: New horizons

Still's disease in children (systemic juvenile idiopathic arthritis - JIA) and adult Still's disease (ASD) are considered as systemic autoinflammatory diseases of unknown etiology, which are based on similar immunopathogenetic mechanisms associated with genetically determined disorders of the mechanisms of innate immunity. ASD was first described 50 years ago by the English rheumatologist Eric George Lapthorne Bywaters. The molecular basis of ASD immunopathogenesis is the activation of innate immunity associated with NLRP3 inflammasome-dependent mechanisms of inflammation, characterized by the overproduction of “pro-inflammatory” cytokines - interleukin (IL) 1 and IL-18, inducing the synthesis of other proinflammatory inflammatory mediators. A review of new data concerning the mechanisms of immunopathology, clinical polymorphism, laboratory biomarkers and the possibilities of ASD pharmacotherapy is presented.Particular attention is paid to the prospects for the use of monoclonal antibodies to IL-1β - canakinumab. The problems associated with the generality of clinical and laboratory disorders, pathogenetic mechanisms and pharmacotherapy of ASD and coronavirus disease 2019 (COVID-19) are considered.

Course and outcomes of COVID-19 in patients with immunoinflammatory rheumatic diseases: Preliminary data from the NIIR/APP-COVID-19 registry and literature review

The materials of the Russian NIIR/ARP-COVID-19 database, which included adult (over 18 years old) patients with immuno-inflammatory rheumatic diseases (IIRD) who underwent COVID-19 (coronavirus disease 2019), and a literature review concerning the course and outcomes of COVID-19 in patients with these diseases, are presented. From July 17, 2020 to April 23, 2021, 156 messages were received and analyzed. The study group was represented mainly by women (75%). The average age of patients was 52.0±14.8 years, of which 53 (33.9%) patients were aged 60 years and older. The most frequent clinical manifestations of COVID-19 were fever (62.2%), cough (40.4%), anosmia (37.8%), shortness of breath (33.3%). During the course of COVID-19, computed tomography of the chest organs was performed in 143 patients. When assessed on an “empirical” visual scale, stage 0 of lung lesion was observed in 49 (34.3%) patients, stage 1 in 40 (28%), stage 2 in 35 (24.5%), stage 3 in 19 (13.2%), stage 4 in 0. In the study group, a favorable outcome was observed in 137 (97.9%) patients. Fatal outcome was registered in 3 patients. The effect of COVID-19 on the course of IIRD was assessed in 131 patients: in 52 (39.7%) patients, the course of IIRD worsened, in 1 (0.8%) it improved, in 78 (59.5%) there was no effect. Literature data on the risk of infection with the SARS-CoV-2 virus, the course and outcomes of COVID-19 in rheumatic and musculoskeletal diseases are contradictory, which dictates the need to continue collecting data on the rheumatological problems of COVID-19 in the Russian patient population, taking into account international experience.