Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening condition associated with the development of thrombotic occlusion of microvasculature vessels, with a mortality rate of about 50%.

The pathogenesis of CAPS is based on cellular activation, complement system induction, cytokine stimulation, inhibition of anticoagulant factors and fibrinolysis, which leads to progressive thrombotic microangiopathy, disseminated intravascular coagulation (DIC), and systemic inflammatory response syndrome. Classification criteria for CAPS include microthrombotic involvement of ≥3 organs (most commonly lungs, kidneys, and central nervous system) for ≤1 week with high titers of antiphospholipid antibodies.

Differential diagnosis is carried out with DIC, heparin-induced thrombocytopenia, hemolytic uremic syndrome, HELLP syndrome, sepsis. Treatment of CAPS in the acute phase involves anticoagulant and immunosuppressive therapy (glucocorticoids, plasmapheresis, IV immunoglobulin, rituximab, eculizumab). Timely diagnosis and adequately selected treatment of CAPS can reduce mortality from 50 to 30%.

Further study of CAPS is needed to improve the prognosis and increase the life expectancy of patients.

Numerous recent studies have shown that TNFAIP3 and TNF-α gene polymorphisms are associated with susceptibility to certain autoimmune and inflammatory diseases, including systemic lupus erythematosus (SLE), systemic scleroderma, rheumatoid arthritis, psoriasis, etc. However, the results of studies on associations between these polymorphisms and the risk of developing SLE in children are ambiguous and few in number.

Objective: to test the hypothesis of a possible association between the rs10499194 polymorphism of the TNFA1P3 gene and the rs1800629 polymorphism of the TNF-α gene with susceptibility to juvenile SLE (jSLE) and its clinical phenotypes in the Russian pediatric population.

Material and methods. Both polymorphisms were studied by allele-specific real-time polymerase chain reaction in 63 children (15 boys and 48 girls) with a confirmed diagnosis of jSLE, whose mean age was 12.3±3.2 years (3–17 years), and the mean duration of the disease was 4.1±2.4 years. Data on the frequency of genotypes and alleles of the corresponding TNFA1P3 and TNF-α gene polymorphisms in 309 healthy unrelated blood donors over the age of 18 years (20–45 years) were used as controls.

Results and discussion. The study showed that the frequency of the rs10499194T mutant allele of the TNFA1P3 gene in patients with jSLE was significantly lower compared to the control (20.6 and 30.7%; p=0.023), and its carriage slightly reduced the risk of developing SLE (odds ratio, OR 0.58; 95% confidence interval, CI 0.32–1.05, p=0.053). The frequency of the rs1800629A mutant allele of the TNF-α gene was slightly higher in jSLE compared with controls (38.1 and 26.2%, respectively; p=0.056), and its carriage slightly increased the risk of developing SLE (OR 1.73; 95% CI 0.93–3.16; p=0.056). An analysis of the frequency distribution of the rs10499194 genotypes in groups of patients with and without arthritis revealed significant differences (p=0.003). Carrying genotypes with the mutant T allele (CT+TT genotypes) in jSLE significantly reduced the risk of developing of arthritis (p=0.003). At the same time, the risk of arthritis in carriers of at least one C allele was 3.76 times higher than in carriers of the other allele (p=0.006). No relationship was found between the rs1800629 TNF-α gene polymorphism and the clinical phenotypes of jSLE.

Conclusion. The rs10499194T mutant allele statistically significant reduces the risk of arthritis development as one of the clinical manifestations of jSLE, and the rs1800629A mutant allele of the TNF-α gene is associated with a tendency to increase the risk of jSLE.

Multisystem inflammatory syndrome in children (MIS-C) is a new and relatively rare nosology in children associated with COVID-19 infection, which is characterized by severe multiple organ involvement and poses an immediate life threat.

Objective: to analyze the clinical, laboratory and instrumental examination data of patients with MIS-C associated with COVID-19 infection, hospitalized in the Republican Infectious Diseases Hospital of the Komi Republic and the Republican Children's Clinical Hospital of the Ministry of Health of the Komi Republic from April 2020 to April 2022.

Material and methods. The retrospective study included 15 patients. The diagnosis was verified according to the Guidelines of the Russian Ministry of Health (version dated July 3, 2020). The results of clinical, instrumental and laboratory examination of patients were evaluated in comparison with literature data.

Results and discussion. The prevalence of MIS-C in the Komi Republic was 5.5 per 100,000 persons under 18 years of age. The majority of the study cohort were males (66.7%), the median age was 3 years. 46.7% of cases were between the ages of 8 and 14 years. At the onset of clinical manifestations, all patients had fever and gastrointestinal symptoms. In 80% of children, pathological changes of skin and mucous membranes, as well as respiratory disorders were revealed. Involvement of the cardiovascular system in the pathological process was noted in 66.7% of cases. Less frequently, the urinary tract was affected. When analyzing laboratory data, an increase in the level of inflammatory markers, as well as lymphopenia and neutrophilia, were noted. Most patients received therapy with intravenous immunoglobulin and systemic glucocorticoids, as well as anticoagulants and acetylsalicylic acid. The outcomes of the disease in most cases were favorable, in 6.7% of patients a lethal outcome was recorded.

Conclusion. The analysis of cases of MIS-C illustrates the high frequency of seroconversion to the SARS-CoV-2 virus, the predominance of males compared to females (2:1 ratio), the prevalence of the age group under 4 years, the heterogeneity of clinical manifestations and generally favorable prognosis. The diversity of clinical features of COVID-19 warrants a high degree of suspicion for MIS-C, as well as the development of a predictive tool, the "MIS-C Suspicion Index".

The “Treat-to-target” (T2T) strategy for axial spondyloarthritis (axSpA) has made it possible to optimize therapy in most patients, but in some of them the treatment goals are not achieved.

Objective: to analyze the clinical features of patients with ankylosing spondylitis (AS) with inefficacy of two or more biological disease modifying antirheumatic drugs (bDMARDs).

Material and methods. From February 2020 to March 2022 458 patients with AS, who met the modified New York criteria of 1984, were admitted to V.A. Nasonova Research Institute of Rheumatology. From this group, 30 (6.6%) patients with high clinical disease activity and inefficacy of at least two bDMARDs were selected. The control group consisted of 139 (30.5%) patients with AS, who either had no history of bDMARDs use, or had previously received only one of them. All patients were examined in accordance with generally accepted methods and underwent a double expert control.

Results and discussion. Men predominated in the main and control groups (67 and 60%, respectively). In patients of the main group, there was a higher laboratory activity of the disease, especially ESR (p=0.002), more often peripheral arthritis was detected. In both groups, there was a high incidence of coxitis (69.2 and 69.7%, respectively), while in the main group there were significantly more patients who underwent total joint arthroplasty, and the frequency of detected syndesmophytes was 2 times lower compared to the control. Differences in the features of AS onset were also established: in the main group, the disease often began with reactive arthritis (ReA), while in the control group, with inflammatory back pain.

Conclusion. The T2T strategy in axSpA does not always lead to the achievement of the intended goals, and, according to our data, among inpatients with AS, the number of people with a history of inefficacy of two or more bDMARDs reaches 6%. In these patients, compared with the control, the following features of the disease can be distinguished: frequent onset with ReA, a significant incidence of peripheral arthritis and joint arthroplasty, and a higher ESR.

Mesenteric panniculitis (MPn) is a rare form of adipose tissue inflammation, mainly of the intestinal mesentery, less often of the omentum, preand retroperitoneal tissue. There are not many descriptions of MPn in rheumatic diseases in the literature: in systemic lupus erythematosus, systemic sclerosis, Sjogren's syndrome, rheumatoid arthritis (RA), ankylosing spondylitis, mesenteric form (MF) of idiopathic lobular panniculitis (ILPn) and IgG4-related disease (IgG4-RD). Given the polymorphism of clinical manifestations, including systemic ones, it is of interest to look at the problem of MPn from the perspective of a rheumatologist.

Objective: to evaluate the clinical and laboratory features of MPn in modern rheumatological practice.

Material and methods. The study included 64 patients (19 men and 45 women aged 19 to 76 years, median disease duration 28.6 [0.3; 243] months). Laboratory and instrumental studies were carried out according to a single algorithm, which included standard clinical, immunological methods, as well as the determination of fecal calprotectin and tumor markers, ultrasound of the skin and subcutaneous adipose tissue (SAT), computed tomography of the chest and abdominal organs, abdominal positron emission tomography, pathomorphological examination of biopsies of the skin, pancreas and mesentery.

Results and discussion. 89% of patients had abdominal pain, 48.4% had nausea, 53.1% had weakness, 44% had subfebrile fever, 32.8% had articular syndrome, and 29.6% – skin and pancreas involvement. Median ESR was 34 [11; 52] mm/h, CRP level – 14 [2; 72] mg/l. Most of the immunological parameters remained within the normal range, but in some cases there was an increase in the concentration of rheumatoid factor, antibodies to the cyclic citrullinated peptide, IgG4. The level of tumor markers CA 125, CEA, CA 19–9 and TumorM2-PK was increased 2 times or more in 5 patients. In our study, all radiological signs and all degrees of severity of MPn were observed. An additional examination confirmed the presence of MF ILPn, RA, IgG4-RD, gastrointestinal, malignant, hematological and other diseases, which made it possible to identify five diagnostic blocks.

Conclusion. Early diagnosis and correct interpretation of the described changes require a lot of work-up and a multidisciplinary approach, which contributes to accurate and timely recognition of the disease.

Osteoarthritis (OA) is a chronic progressive joint disease that leads to disability. One of the main treatment approaches in OA is to reduce pain and increase the functional activity of patients.

Objective: to evaluate the efficacy, tolerability and safety of Meloxicam Canon (MC) in the form of a 1% gel for external use as a symptomatic therapy in patients with knee OA, accompanied by pain.

Material and methods. The randomized, open, multicenter study included 100 patients aged 50 to 80 years with stage II–III knee OA, who were randomized into two groups in a 1:1 ratio. In the main group, patients applied MC gel topically, and in the comparison group –Amelotex® gel. Patients were examined at baseline, and after 7, 14 and 28 days. The following indicators were studied: intensity of pain during movement on a visual analogue scale (VAS), affected knee circumference (AKC); Lequesne and WOMAC indices; patient global health assessment (PGHA) according to VAS; response to therapy, tolerability according to the number of adverse reactions (AR), safety according to blood and urine tests.

Results and discussion. Pain intensity according to VAS by the end of the observation period decreased on average by 65.0±25.6% in the main group, and by 62.8±29.1% in the comparison group (p<0.0001 for each group). AKS significantly decreased by visit 3 in both groups. There was an improvement in PGHA by VAS by 69.7±24.3 and 66.6±26.8% on average, respectively (p><0.0001 for each group). The average decrease in the Lequesne index was 55.0±30.1 and 52.8±38.3%, and in the WOMAC index – 58.9±30.8 and 59.3±31.8%, respectively, in the main group and comparison group (p><0.0001 in each group for both indices), while there were no differences in the dynamics of all indicators between the two groups (p>0.05). During the observation, no negative dynamics in patients’ condition in both groups was noted. No serious ARs or deaths were recorded during the study.

Conclusion. The conducted multicenter study demonstrated that MC gel is an effective and safe drug for local use in OA, accompanied by pain.

Local forms of non-steroidal anti-inflammatory drugs (NSAIDs) are characterized by a high safety profile due to low systemic absorption. They do not increase the risk of developing class-specific gastrointestinal, cardiovascular and kidney adverse events (AEs), which makes it possible to prescribe them even in severe comorbid pathology, which is typical for patients with osteoarthritis (OA).

Objective: to evaluate the efficacy and safety of Artoxan gel (tenoxicam) 1% in comparison with Diclofenac gel 1% in patients with knee OA in a prospective comparative randomized trial.

Material and methods. The study included 60 patients with Kellgren–Lawrence stages II–III knee OA, aged 41 to 78 years. The patients were randomly divided into two groups: the 1st group received Artoxan gel 1%, 5 cm 2 times a day for 14 days; 2nd – Diclofenac gel 1% according to the same scheme. During therapy, we assessed pain using a visual analog scale, the WOMAC index, quality of life using the EQ-5D questionnaire, satisfaction with therapy, and time to effect.

Results and discussion. It has been demonstrated that local forms of NSAIDs have a positive effect on all clinical manifestations of OA: effectively reduce pain, stiffness, improve the functional state of the joints and quality of life. They also have a good safety profile and a fast symptomatic response. Comparison of the two groups showed that in patients receiving the local form of tenoxicam, there was a tendency to a more rapid and pronounced analgesic effect.

Conclusion. The results of the study confirm the good efficacy and safety of local forms of NSAIDs. 

Marble disease, or osteopetrosis (OPT), is rare in the practice of a rheumatologist, internist or pediatrician. This group of hereditary diseases is based on a defect in the formation, development and functioning of osteoclasts (OCL), which leads to disruption of the processes of resorption and remodeling of bone tissue. Disturbance of resorption leads to increased density and changes in the quality of the bones, as a result of which they become more fragile. As a rule, the disease manifests with pathological fractures. In recent decades, 70% of patients with OPT have been found to have mutations in at least 10 genes that lead to impaired functioning of the OCL. Depending on the variant of inheritance, autosomal dominant, autosomal recessive and intermediate types of OPT are distinguished. Autosomal dominant OPT has a benign course that can be asymptomatic or characterized by multiple bone fractures and other spinal anomalies. The disease usually manifests in adulthood or adolescence. Life expectancy in patients of this group does not differ from that in the general population. Malignant, or infantile, OPT is associated with an autosomal recessive inheritance pattern. Its clinical manifestations are observed from the moment of birth, without treatment, patients die within the first decade of life. In such patients, in addition to the skeletal pathology, there is involvement of the hematopoietic system, compression of the cranial nerves and their function disturbance.

The article presents a clinical case of autosomal dominant OPT diagnosed in adulthood (at the age of 38), when the patient referred to the doctor for the first time. Differential diagnosis with ankylosing spondylitis and paraneoplastic spondyloarthritis was performed.

A clinical case of the development of rapidly progressive systemic sclerosis after repeated coronavirus infection is described. The contribution of occupational hazards, the oncological process and radiation therapy to the pathogenesis of this disease is discussed. Hydropericardium was a feature of the clinical picture, as well as rare immunological markers of the late onset of systemic sclerosis.

Obliterative (constrictive) bronchiolitis (OB) is a rare disease characterized by destruction of the bronchiolar epithelium and subsequent progressive airway obstruction. OB is most common in rheumatoid arthritis (RA) compared to other systemic rheumatic diseases. Clinical manifestations of OB are found mainly with a long duration of RA and the absence of adequate therapy for articular manifestations. We present a clinical observation, demonstrating the distal respiratory tract involvement in a patient with RA during the first year of the disease, which is observed in no more than 10–20% of cases. The nonspecificity of respiratory symptoms on the background of immunosuppressive therapy led to a diverse differential diagnostic spectrum of pulmonary pathology. For timely diagnosis and optimization of therapeutic approaches, clinical suspicion for respiratory lesions in patients with RA and interdisciplinary cooperation are necessary.

Gout is a chronic inflammatory arthropathy, caused by articular and periarticular sodium monourate (MUN) crystals deposition on the background of chronic hyperuricemia. Gout belongs to the group of autoinflammatory diseases characterized by activation of the innate immune system. In some cases, especially in women, with a long course of the disease and absence of adequate therapy, chronic arthritis is detected, which has little difference from that in rheumatoid arthritis (RA). At the same time, until recently, the combination of RA and gout was considered casuistry due to the inhibition of crystal formation by specific factors associated with RA, what is more mechanisms of inflammation development characteristic of these diseases are completely different. However, according to the latest data, the coexistence of these two diseases in one patient is possible, and the therapy of both, gout and RA (in some patients) can be successful when prescribing biological disease modifying antirheumatic drugs, in particular inhibitors of the interleukin 1 receptor (IL1r).

The article presents a rare clinical case of chronic tophi gout in an elderly patient who was followed up for a long time with a diagnosis of RA, a significant improvement was achieved on therapy with the IL1r antagonist anakinra.

The goal of treatment of rheumatoid arthritis (RA) is to achieve remission or low disease activity. A wide range of disease-modifying antirheumatic drugs is used for the treatment of RA, including biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi). However, even with the use of bDMARDs and JAKi, this goal can be achieved only in 40–60% of patients. Insufficient response to bDMARs and JAKi is the reason for switching to other drugs from the same group, such as tumor necrosis factor-α inhibitors, and to drugs with a different mechanism of action. The need to change therapy may be associated with its ineffectiveness due to various immune, genetic and epigenetic mechanisms, with the development of adverse reactions, as well as with comorbid pathology. To date, there is no certain predictors of effectiveness of a particular bDMARDs and JAKi and of the need and strategy for changing the therapy.

The review considers the effectiveness of various classes of bDMARDs and JAKi in RA, the frequency and risk factors associated with the need to switch patients to other drugs, the role of chemokines as promising markers of response to RA treatment.

Glucocorticoids (GCs) are one of the most commonly used drugs for the treatment of rheumatoid arthritis (RA), the effectiveness of which is beyond doubt. The review considers current literature data on the safety of GCs use, as well as the most common adverse events associated with such therapy. Most authors point to an increased risk of complications with an increase in the daily dose and/or duration of GCs treatment. At the same time, a safe dose of GCs has not been determined. Probably, the optimal tactic is the selection of an individual dose of GCs in each individual case, taking into account the activity of RA and the spectrum of comorbid conditions. In this case, the minimum effective doses and short courses of GCs should be used, regular monitoring of clinical and laboratory parameters should be carried out in order to detect adverse events early.

The article discusses the relevance of determining DNA double-strand breaks (DSBs) using the analysis of γ-H2AX foci as a marker of DNA instability in various conditions. The issues of the formation of DSBs and the peculiarities of their detection in various tissues are highlighted. Changes in the intensity of DSBs formation during the use of radiological diagnostic methods, stress, increased physical exertion, some oncological and rheumatic diseases, as well as the dynamics of DNA repair on the background of various methods of therapy were analyzed.

Treatment of such a serious systemic disease as gout is often carried out incorrectly, despite the presence of a large number of recommendations and drugs. The reluctance of some doctors to follow current recommendations for the management of patients with gout is one of the factors for poor adherence of patients to therapy. The review considers modern approaches to the treatment of gout, which provide for long-term strategies for lowering of serum uric acid level.

Chronic shoulder pain (CSP) is a clinical syndrome associated with inflammatory and degenerative musculoskeletal changes, characterized by pain in the shoulder that persists for at least 3 months, arising or aggravated by functional activity in this area. The frequency of CSP in the modern population reaches 20–33%, it is one of the leading causes of severe suffering, disability and seeking for medical attention.

 The main causes of CSP are shoulder rotator impingement syndrome (subacromial impingement syndrome), calcific tendinitis, adhesive capsulitis, shoulder and acromioclavicular joint osteoarthritis. Accurate diagnosis of these diseases is necessary for the correct choice of treatment. Differential diagnosis is carried out using tests that evaluate the function of the shoulder joint and the rotator cuff muscles (Neer, Speed, Hawkins tests, etc.), as well as using instrumental methods (ultrasound, magnetic resonance tomography, X-ray). In CSP, it is necessary to exclude septic, oncological, visceral, systemic rheumatic and other diseases, as well as musculoskeletal pathology of the cervical spine, upper chest and back, which can cause pain in the shoulder region.

Therapy for diseases that cause CSP should be personalized and complex, aimed at maximum pain control and restoration of function. For this purpose, non-steroidal anti-inflammatory drugs, local injection therapy with glucocorticoids, hyaluronic acid, and platelet-rich plasma are used. In some cases, muscle relaxants, antidepressants, anticonvulsants, local injections of botulinum toxin type A are indicated. Physiotherapy and medical rehabilitation methods play a fundamental role in the treatment of CSP.

Musculoskeletal diseases, such as osteoarthritis (OA), nonspecific back pain (NBP), and periarticular soft tissue pathology (PSTP – tendinitis, enthesitis, bursitis, etc.) are one of the most common reasons for visiting general practitioners. The treatment of this pathology is based on the complex use of drugs and non-drug methods for maximum pain control and lost function restoration. Considering the common pathogenesis of musculoskeletal pain in OA, NBP, and PSTP, it is advisable to base the therapy of these diseases on a single algorithm. Of course, when prescribing treatment, one should take into account "red flags" (symptoms of life threatening diseases), features of the clinical course, patient's psycho-emotional condition, and comorbid diseases.

Development of a unified tactic for the treatment of musculoskeletal pain will significantly reduce the time spent on a diagnostic search and the choice of adequate therapy, which will facilitate the work of a general practitioner. Thus, non-drug approaches (patient education, kinesiotherapy, psychotherapeutic methods, etc.), non-steroidal anti-inflammatory drugs (NSAIDs) and symptomatic slow-acting drugs (SYSADOA) seem to be the most rational approach in the debut of the treatment of OA, NBP and PSTP. Among NSAIDs, celecoxib seems to be one of the optimal drugs in terms of efficacy and safety, and among SYSADOAs – diacerein. There is evidence that the combined use of these drugs may increase their analgesic and anti-inflammatory potential.