VA Nasonova Scientific Research Institute of Rheumatology

Autoinflammatory diseases (AIDs) represent a heterogeneous group of conditions pathogenetically associated with dysregulation of innate immunity and clinically characterized by recurrent episodes of sterile inflammation in affected organs in the absence of infection, allergy, and high titers of circulating autoantibodies or autoreactive T cells. The overwhelming majority of monogenic AIDs (mAIDs) are accompanied by skin rashes, the type of which is determined by the specific disease and, to some extent, by differing pathogenetic mechanisms. The first part of the article presents the cutaneous characteristics of the most common mAIDs: Familial Mediterranean fever (FMF), cryopyrinassociated periodic syndromes (CAPS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), periodic syndrome with hyperimmunoglobulinemia D / mevalonate kinase deficiency (HIDS/MKD). Skin involvement in these diseases reflects systemic inflammation associated with hyperproduction of the key pro-inflammatory cytokine interleukin (IL)-1β. In other AIDs, symptoms mainly depend on increased levels of cytokines such as IL-18, IL-36, etc. (NLRC4-associated autoinflammatory disease; deficiency of the IL-36 receptor antagonist – DITRA), as well as activation of interferon signaling pathways (interferonopathies). Different pathogenetic mechanisms determine the diversity of clinical phenotypes, including cutaneous manifestations. Knowledge of these features helps establishing a correct diagnosis, obtaining genetic confirmation (without which accurate identification of these rare conditions is impossible today) and selecting appropriate therapy. Pathological examination plays a special auxiliary role and should be used in diagnostically challenging situations.

BACKGROUNDJuvenile arthritis damage index (JADI) is a tool that measures the degree of aggressiveness of the juvenile idiopathic arthritis (JIA) course and assesses articular [JADI - articular damage (JADI-A)] and extraarticular [JADI - extraarticular damage (JADI-E)] damage. While aggressive JIA often requires early biologic disease-modified antirheumatic drugs (bDMARDs), the utility of JADI as a predictor of treatment response remains underexplored.AIMTo evaluate the potential of JADI as a predictor of bDMARD treatment response in JIA patients.METHODSThis prospective study included 112 highly active non-systemic JIA biologic-naïve patients with a mean age of 12.2 ± 4.6 years and a median disease duration of 2.5 (interquartile range: 1-5) years. Their clinical and radiological assessment, juvenile arthritis disease activity score 71, JADI-A, and JADI-E, were evaluated twice: Before the biologic initiation (baseline) and 12 months after (end of study). At baseline, 50% had any damage, with 43% with articular damage and 23% with extraarticular damage.RESULTSDuring the study, JADI-A/JADI-E improved (33.9%/9.8%), worsened (8.9%/5.4%), or remained unchanged (57.1%/84.8%). Patients with baseline damage had higher markers of JIA activity: Polyarticular course, earlier onset age, ANA-positivity, and more active joints. Patients without initial structural damage (JADI“-“) were more likely (odds ratio = 3.8, 95% confidence interval: 1.6-9.0, P < 0.004) to achieve a low degree of activity or remission (46.2%), while on biological therapy, their scores were comparable to JADI-positive (18.3%). Pre-biological joint damage according to the JADI-A index (P = 0.003), wrist (P = 0.035), elbow (P = 0.027), cervical spine limitation of motion (P = 0.051), and erosions confirmed by magnetic resonance imaging (P = 0.002), were associated with poor response to biological treatment and follow-up JIA activity.CONCLUSIONBaseline structural damage in JIA is associated with diminished bDMARDs efficacy, increased disability, and shorter remission duration. JADI enhances conventional clinical risk stratification by facilitating timely initiation of bDMARDs, adherence to treat-to-target strategy and tailored patient care.

Introduction . Rheumatoid arthritis (RA) is a disease characterized by epidemiological sexual dimorphism (affecting predominantly women). For many of women, the onset of the disease occurs around menopause, making it important to analyze the relationship between RA and estrogen deficiency. Aim. To study the clinical features of RA in women depending on the age of menopause. Materials and methods . A retrospective study of 246 postmenopausal women with an established diagnosis of RA in postmenopause was conducted. Patients were divided into subgroups depending on the age of menopause: early (before 45 years, n = 71) and timely menopause (≥45 years, n = 175), a comparison of quantitative and qualitative indicators was made between the subgroups. In the subgroup with early menopause, a division was made depending on the natural (n = 46) or surgical cause (n = 25) of its onset, followed by an intergroup comparison. Results. Women with early menopause were comparable with the group with timely onset of menopause in terms of the main clinical and laboratory parameters characterizing RA. Women with natural early menopause, compared with early surgical menopause, were characterized by significantly higher levels of C-reactive protein (6.45 [3.35; 22.33] mg/L vs. 3.20 [1.70; 10.90] mg/L; p = 0.03) and ESR (28.50 [16.50; 58.00] mm/h vs. 16.00 [11.00; 29.00] mm/h; p = 0.021), as well as trends toward higher DAS28 activity (p = 0.06), more swollen joints (4.50 [2.25; 8.00] vs. 3.00 [1.00; 6.00]; p = 0.089), and a higher incidence of erosive arthritis (78.3% vs. 56.0%; p = 0.077). On the other hand, early surgical menopause was associated with a higher incidence of cardiovascular disease and hypertension (72.0% versus 34.8%; p = 0.003), as well as higher fasting glucose levels (5.49 [4.88; 5.79] mmol/l versus 5.00 [4.79; 5.40] mmol/l; p = 0.03) compared to women with early natural menopause. Conclusions . The age of menopause in our sample did not have a significant effect on the clinical course of RA, but women with early natural menopause had higher rates reflecting the inflammatory activity of RA, and women with early surgical menopause more often suffered from metabolic disorders.

In immuno-mediated rheumatic diseases (IMRD), laboratory biomarkers, which include autoantibodies, proteins of the acute phase of inflammation, cytokines, markers of endothelial damage, components of the complement system, subpopulations of lymphocytes, indicators of bone metabolism, and many others, occupy a central place in the diagnosis, assessment of activity, and monitoring of the effectiveness of pharmacotherapy. In the range of biomarkers of inflammation in recent years, special attention has been drawn to calprotectin (CP), which is a heterodimeric complex of S100A8 and S100A9 calcium-dependent proteins. Currently, to characterize inflammation in IMRD, attention is drawn to determining the concentration of CP in biological fluids, the so-called circulating or serum (s) CP, an increase in the concentration of which may be more associated with local (in situ) than with systemic synthesis of protein. The narrative review summarizes the clinical significance of the sCP determination in IMRD as a new biomarker of inflammation. Preliminary recommendations regarding indications for determining the sCP in IMRD are presented.

The aim of the study – to evaluate the safety and influence of tenoxicam (Texared®) on the duration and severity of morning stiffness, spinal pain at night, activity and function in patients with ankylosing spondylitis (AS) Materials and methods. The study included 30 patients (aged 18 to 60) with AS who sequentially sought medical care at the V.A. Nasonova Research Institute of Rheumatology and voluntarily signed an informed consent form to participate in the study. Most patients (66.7%) were male. The average age of patients was 37.6±9.5 years, and the average duration of the disease was 134.5±92.3 months. HLA-B27 antigen positivity was detected in 76.7% of cases. All patients who voluntarily agreed to participate in the study and signed an informed consent form at the initial visit were prescribed tenoxicam (Texared®) at a daily dose of mg. At week 0, 14 days and 90 days (3 months) after the start of therapy, standard clinical and laboratory examinations were performed. Results and discussion. On the background of regular tenoxicam administration, most patients with AS achieved a reduction in clinical parameters of disease activity compared to baseline and its dynamics after 90 days: a decrease in BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) indices to 3.8 (p&lt;0.016) and ASDAS (Ankylosing Spondylitis Disease Activity Score) to 2.8±1.3 (p&lt;0.011) was noted; the severity and duration of morning stiffness to 3.9±2.5 and 3.0±2.7 (p&lt;0.01 in both cases), respectively; patient assessment of disease activity to 4.1±2.2 (p&lt;0.00); night-time back pain – to 3.0±2.6 (p&lt;0.00). After 14 days of treatment, one third of patients achieved a 20% improvement according to ASAS (Assessment of SpondyloArthritis International Society) criteria. After 90 days, the number of responders was 70.3%. Tolerability of therapy was good in 44.4% of cases. No serious adverse events were recorded during the study. Conclusion. In patients with high and very high AS activity, tenoxicam (Texared®) therapy has been shown to have a positive effect on disease activity, including the severity of night-time back pain and the severity and duration of morning stiffness. The drug is well tolerated and has a favourable safety profile.

Nonsteroidal anti-inflammatory drugs (NSAIDs) occupy one of the central positions in the multimodal control of acute and chronic musculoskeletal pain and have broad indications, including rheumatic diseases. Lornoxicam, an oxicam-class NSAID, is a balanced cyclooxygenase (COX)- 1/COX-2 inhibitor characterized by rapid onset of its effect, fast elimination, and a short half-life, which reduces the risk of its accumulation and provides good tolerability. Therapeutic equivalence has been demonstrated among the three lornoxicam formulations (Xefocam tablets, Xefocam injection, and Xefocam Rapid), obviating the need for dose adjustment when switching from parenteral to oral administration.

Objective. To compare serum concentrations of galectins 1, 3 and 9 in women with systemic lupus erythematosus (SLE) and healthy donors; to assess the relationship of these biomarkers with disease activity and specific clinical manifestations.Material and methods. This cross-sectional study included women with SLE (n=121) and women without immune-inflammatory rheumatic diseases (n=21; control group). Serum levels of galectins 1, 3 and 9 were measured using enzyme-linked immunoassay (Cloud-Clone Corp., China).Results and discussion. Levels of all three galectins were higher in SLE patients compared with the control group. Weak correlations were found between SLEDAI-2K and galectin 1 (r=0.33, p=0.0003) and galectin 3 (r=0.26, p=0.005), and between the damage index and galectin 3 (r=0.2, p=0.04). In patients with SLE and cutaneous involvement, arthritis, or hemolytic anemia, serum galectin 1 was higher than in patients without these manifestations. Women with nephritis and serositis had higher galectin 3 concentrations than those without such features. Patients with SLE and antiphospholipid syndrome (APS) had lower galectin 1 levels, whereas those with secondary Sjцgren’s syndrome (SS) had higher concentrations of galectins 3 and 9. Anti-dsDNA antibody levels correlated with galectin 1 (r=0.19, p=0.039), galectin 3 (r=0.2, p=0.027), and galectin 9 (r=0.19, p=0.034) concentrations, while C3 and C4 complement levels correlated only with galectin 9 concentrations (r=-0.19, p=0.04 and r=-0.18, p=0.045, respectively).Conclusion. Serum concentrations of galectins 1, 3 and 9 are elevated in women with SLE. Levels of galectins 1 and 3 show weak associations with SLE activity, while galectin 3 levels correlates with the severity of irreversible damage. Certain clinical features of SLE are associated with higher levels of these biomarkers: for galectin 1 – cutaneous involvement, arthritis, hemolytic anemia, absence of APS; for galectin 3 – nephritis, serositis and SS; for galectin 9 – SS.

Takayasu arteritis (TA) is a rare systemic disease characterized by granulomatous inflammation affecting large arteries, primarily the aorta and its branches. First described in Japan, where the disease has a high prevalence, TA was subsequently reported, though less frequently, in other ethnic groups. Rare cases of familial aggregation suggest the involvement of genetic factors in the pathogenesis of TA. During nearly 45 years of genetic research on TA, a strong association has been established with the HLA-B5(52) antigen/HLA-B*5201 allele, as well as with other HLA and non-HLA molecular genetic markers.

The aim of the study was to determine the frequency, assess survival, and characterize the clinical features of systemic lupus erythematosus (SLE) in association with pulmonary arterial hypertension (PAH).Material and methods. According to the results of echocardiographic screening, 8 patients with PAH-SLE were identified after verification of the diagnosis on a right heart catheterization. Two cohorts of patients with SLE observed at the V.A. Nasonova Research Institute of Rheumatology were taken as a comparison group: the first is historical, with a long follow-up period (n=154), the second is modern, with a short duration of the disease (n=400). The analyzed patient groups were examined according to a single scheme, differences in signs and survival were assessed. The intrahospital frequency of PAH in SLE was estimated based on statistical data for the period from 2008 to 2017.Results. Despite the small number of patients in the main group, signs associated with the presence of PAH were identified: predominantly chronic course of SLE, with a long period (6–11 years) the course of the disease before the first clinical signs of PAH, the presence of Raynaud’s syndrome without capillaroscopic changes, Roand Smithautoantibodies. The survival rate of patients with PAH-SLE and the long-term observed SLE cohort did not differ. The in-hospital prevalence of SLE with echocardiographic screening was 0.29%.Conclusion. PAH is a rare manifestation of SLE associated with the features of the course and clinical picture, which does not significantly affect survival when using PAH-specific therapy.

The expert council evaluated the appropriateness of using a preparation containing a combination of B-group vitamins in the multimodal treatment of pain associated with osteoarthritis (OA). Theoretical rationale, clinical trial data, and meta-analyses support the consideration of high-dose B vitamin complexes as an effective component of combination therapy for musculoskeletal pain in OA.