The concept of a 'health care realm' is introduced. The healthcare realms considered were those patients who have only Physical Health Problems (PH), patients with neither physical nor mental health issues and who are seeking advice to remain healthy (HP), patients only with Mental Health Problems (MH), patients with both Physical Health and Mental Health Problems (PH&MH) and patients with Psychosomatic Health conditions (PS). Described is how patients' minds and bodies interact and its relevance to rheumatology practice. Presented is the culmination of 34 years of the author's experience of rheumatological disorders based in Family Medicine in a United Kingdom General Practice. Also presented are 2 small studies supplementing the main conclusions. The first small study counted the main consultation content of 246 patients, as considered by the principals in the practice. Of these 73.5% were for physical health conditions, 13.3% for health promotion, 11.5% for mental health conditions and 1.8% for psychosomatic conditions. The second small study was a survey of experienced GPs, Physicians and Psychiatrists, asking about their opinions on how well the patients in different health care realms were being managed across the healthcare system. Of the 5 realms, the collective view was that it was the patients in the PH realm who was clearly received the best care. The least good care was being given to patients in the PS realm and only marginally better were patients in the MH Realm. This paper argues that clinicians need a different thinking approach when meeting patients from different healthcare realms. It is known that when doctors treat PH patients, they consider the patient's symptoms against templates of knowledge for the conditions in the differential diagnosis. Furthermore, HP patients are assessed by comparing the patient's bio-measurements against known markers of good health When being consulted by patients in the MH or PS realms, it is advocated, not to follow the approach of PH patients. For patients in the MH realm it is best to address the patient's life as a whole and to consider, how did the person arrive to the situation he is in and what needs to be done to restore the patient's life back on track. For patients in the PS realm, ideally the aim is to help the patient make the link between the physical symptom and its psychological aetiology. A step towards this is to describe how the body physically mediates the symptom.

Objective: to evaluate changes in T- and B-lymphocyte subpopulations at different stages of rheumatoid arthritis (RA).

Patients and methods. The study included 53 patients with a definite RA diagnosis according to the 2010 ACR/EULAR criteria (mean age 54.2 [47; 62] years). Group 1 included 27 patients (25 women and 2 men) without history of synthetic disease modifying anti-rheumatic drugs (sDMARDs) intake, group 2 included 26 patients (22 women and 4 men) receiving sDMARDs (methotrexate or leflunomide). The control group consisted of 29 healthy volunteers (23 women and 6 men), the median age was 58.5 [53; 62] years. In all participants flow cytofluorometry according to the standard technique with immunophenotyping of T- and B-lymphocytes was performed.

Results and discussion. Compared to controls, patients in group 1 who had not previously received sDMARDs showed a transient increase in "switched" memory B-cells, transient B-cells, and plasmablasts, which was not observed in patients of group 2 (on sDMARDs therapy). Patients with advanced RA showed a statistically significant decrease in the absolute and relative number of memory B-cells, the absolute and relative number of "switched" B-lymphocytes, as well as the number of plasmablasts and transient cells. In RA patients, a statistically significant rela tionship was established between the number of swollen joints and the level of plasmablasts (r=0.51), memory cells (r=0.54), and "switched" B-cells (r=0.41), p< 0,05 in all cases. There were no statistically significant changes in other subpopulations of B-lymphocytes and the profile of T-lymphocytes.

Conclusion. Changes in the B-lymphocyte profile are characteristic of different stages of RA. At an early stage, there is an increase in the number of transient B-lymphocytes, plasmablasts and plasmocytes, and in the advanced stage, a decrease in the level of certain populations of B-lymphocytes, such as memory B-cells and "switched" B-lymphocytes. It can be assumed that the ineffectiveness of sDMARDs is associated with a change in the population composition of B-lymphocytes, which requires further study.

Objective: to test the hypothesis of a possible relationship between the rs12218 polymorphism of the SAA1 gene and a predisposition to different clinical phenotypes of juvenile idiopathic arthritis (JIA).

Patients and methods. Genetic typing of rs12218 polymorphism was carried out in 142 children: 77 of them were diagnosed with JIA, including 30 patients with oligoarthritis (oJIA), 20 with polyarthritis (pJIA), and 27 with systemic onset (sJIA). Sixty five healthy volunteers were included in the control group. The rs12218 polymorphism of the SAA1 gene was investigated using real-time polymerase chain reaction.

Results and discussion. A high risk of developing the clinical phenotype of oJIA in carriers of the C mutant allele of the rs12218 T/C polymorphism of the SAA1 gene was established. Statistically significant differences between the clinical phenotypes of oJIA and sJIA in the frequency distribution of genotypes and alleles of rs12218 T/C polymorphism of the SAA1 gene are shown.

Conclusion. The results of the studies have confirmed the important role of the rs12218 T/C polymorphism of the SAA1 gene in the formation of susceptibility to clinical variants of JIA.

Extensive use of magnetic resonance imaging (MRI) in clinical practice revolutionized our understanding of the pathogenesis of axis spondyloarthritis (aSpA) and treatment approaches. The use of MRI to diagnose non-radiographic aSpA is well established. At the same time, the possibility of its use for follow-up and treatment assessment is actively discussed.

Objective: To present comparative analysis of clinical and laboratory data, reflecting the activity of the disease, and analysis of MRI results in patients with ankylosing spondylitis (AS) receiving biological disease modifying anti-rheumatic drugs therapy (bDMARDs).

Patients and methods. The study included 39 patients with AS, mainly men (74.3%), 24 patients (61.5%) had late and 15 (38.5%) – advanced stage of the disease. The average age was 41.0 [34.0; 48.0] years. All patients were administered bDNARDs; inhibitors of the tumor necrosis factor α or inhibitors of interleukin 17 were drug of choice. The median of treatment duration was 1.5 [1.0; 4,5] year. All patients had sacroiliac (SI) and spinal MRI. The activity of the disease was estimated using BASDAI and ASDAS-CRP/ESR indexes, functional disorders – using the BASFI questionnaire. Results and discussion. There was no significant difference in disease activity between patients with osteitis in the SI/spine or without it: BASDAI – 4.7 [2.7; 5,5] and 4.2 [2.9; 8,1], respectively (p=0.533); ASDAS-ESR – 2.6 [2.2; 3,0] and 2.6 [2.2; 3,2], respectively (p=0.725); ASDAS-CRP – 2.5 [2.1; 3,4] and 3.1 [2.8; 3.9], respectively (p=0.172). There was no significant difference in the number of osteitis foci between group of patients who have achieved the therapeutic target (ASDAS < 2.1) and those who have not (ASDAS ≥2.1) – 1.0 [0.0; 3.5] and 1.0 [1.0; 4.0], respectively, (p=0.376), and no difference in amount of inflammatory changes – 1.0 [0.2; 1.7] and 0.1 [0.0; 1,1] cm3, respectively (p=0.124). Conclusion. The data suggests a limited MRI informative value as a method for managing the efficacy of bDMARDs treatment in patients with the advanced / late stage of the AS.

Objective: to compare results of ultrasound examination (US) of the wrist joints (WJ) and small joints of hands with the clinical signs in patients with early rheumatoid arthritis (eRA) and hand osteoarthriti (OAH).

Patients and methods. The study included 42 patients with eRA (group 1) and 38 patients with OAH (group 2). The average age of patients with eRA was 48.60±14.86 years, the duration of clinical manifestations was 7.45±1.77 months, of patients with OAH – 54.97±12.45 years and 8.26±1.83 months, respectively. The ratio of men and women in both groups was approximately the same, the majority were women. All patients with eRA had clinical and instrumentally confirmed signs of OA: I, II, and III radiological stages of OA according to Kellgren–Lawrence were detected in 10 (23.80%), 23 (54.76%) and 9 (21.43%) patients respectively. In erosive OA II and III X-ray stage was diagnosed in 16 (42.10%) and 22 (57.90%) patients, respectively. All patients underwent ultrasound of the joints, as well as a general clinical examination, which included an assessment of the number of painful joints, the number of swollen joints, and a general assessment of pain intensity using a visual analogue scale (100 mm). RA activity was determined using the DAS28 index. We also studied laboratory parameters – the levels of CRP, rheumatoid factor and antibodies to cyclic citrullinated peptide in blood serum.

Results and discussion. Comparison of the two groups of patients showed that ultrasound in B-mode and power Doppler mode with eRA and OAH showed more pronounced inflammatory and destructive changes in the wrist joints and small joints of the hands, with the exception of the distal interphalangeal joints (DIPJ). In addition, only in patients of the 1st group there was a close correlation between the enhancement of the Doppler signal and levels of inflammatory markers. Conclusion. eRA compared with OAH is characterized by more pronounced ultrasound signs of inflammatory and destructive changes in the wrist joins and small joints of the hands, with the exception of DIPJ.

Objective: to study the contribution of neurogenic mechanisms to the pathogenesis of chronic pain in patients with rheumatoid arthritis (RA), knee osteoarthritis (OAk) and ankylosing spondylitis (AS). To evaluate the effectiveness of an anticonvulsants in complex therapy of RA and OAk.

Patients and methods. The study included 518 patients, 208 (40.2%) had definite RA, 160 (30.9%) had OAk and 150 (28.9%) had AS. All patients were rheumatologically and neurologically examined to determine the state of the somatosensory system; DN4 and Pain DETECT questionnaires were used to diagnose pain descriptors characteristic of neuropathic and nocyplastic pain; visual analogue scale (VAS) was used for pain intensity at rest assessment; algometry – for detecting secondary hyperalgesia. Functional, affective disorders and quality of life were assessed as well. Moreover, efficacy of the anticonvulsant in the complex therapy of RA and OAk was evaluated.

Results and discussion. 49.5% of RA patients had neuropathic pain. It has been statistically significantly shown that older patients with a long history of the disease, advanced X-ray stage and high level of anxiety and depression experience neuropathic pain more frequently. Disease activity and ESR level did not affect the severity of the neuropathic component of pain. In 37.5% of OAk cases, signs of nociplastic pain were observed. Patients in this group were in pain according to VAS, worse functional state and quality of life, as well as a higher level of anxiety, the differences were statistically significant. 12.7% of AS patients had nociplastic pain. There was no association with the age and duration of the disease. Higher levels of disease activity, pain and depression and worse functional abilities were observed when nociplastic pain was present. The effectiveness of anticonvulsant is demonstrated in the complex therapy of chronic articular pain in RA and OAk, which confirms the role of central sensitization in the pathogenesis of pain in these diseases.

Conclusion. Chronic pain in RA, OAk and AS patients in some cases has mixed nature, both inflammatory and neurogenic mechanisms (neuropathic and nociplastic) are involved. It is necessary to examine patients to identify the neuropathic component of pain, which will improve pain control and ensure a holistic approach to therapy. In patients with RA and OAk, having a mixed nature of pain, complex treatment, containing a central action drug from a group of anticonvulsants, is more effective compared with standard anti-inflammatory therapy.

Non-steroidal anti-inflammatory drugs (NSAIDs), colchicine and glucocorticoids (GC) are used to prevent arthritis attacks in gout, but data on their comparative effectiveness is lacking.

Objective: to compare the efficacy and safety of various anti-inflammatory drugs at the start of treatment in patients with gout.

Patients and methods. Of the 108 patients with gout, observed in the V.A. Nasonova Research Institute of Rheumatology, 97 (94%), mostly men, entered a single-center prospective study. The observation period was at least 24 weeks, patients received combined urate-lowering and prophylactic anti-inflammatory therapy unintermittingly. The control group included 12 patients in whom anti-inflammatory drugs were contraindicated. At the start of urate-lowering therapy, allopurinol 100 mg per day was prescribed, followed by dose titration until the target uric acid (UA) level of < 360 μmol/L level was reached, in patients with severe tophus gout it was < 300 μmol/L. The maximum dose of allopurinol was 900 mg per day; in patients with reduced glomerular filtration rate (<60 ml/min/1.73m2 ) – 300 mg per day. For the prevention of arthritis attacks, the drug of choice was colchicine 0.5 mg per day, when contraindicated and/or poorly tolerated, NSAIDs were prescribed in the minimum effective dose. If there were any NSAIDs use restriction or intolerance – prednisone 7.5 mg per day was administered. The effectiveness of anti-inflammatory therapy (NSAIDs, colchicine or GC) was evaluated after 3 and 6 months which included analysis of the frequency of exacerbations and the duration of arthritis attacks, the intensity of pain according to the visual analogue scale (VAS) during a gout attack.

Results and discussion. Of 97 patients with gout, 85 (88%) received anti-inflammatory therapy: NSAIDs – 16 (19%), colchicine – 60 (71%), GC – 9 (10%). In 65% of patients who were administered anti-inflammatory therapy, there were no recurrence of arthritis, whereas in 12 patients of the control group who did not receive this treatment, recurrence of arthritis was absent only in 25% of cases (p=0.008). After 3 and 6 months of follow-up, the duration of gout attacks and the intensity of joint pain according to the VAS for recurrent arthritis were significantly less (p< 0.05 in both cases) in the treatment group (with any anti-inflammatory drug) than without treatment. Arthritis attacks were more likely to be absent when taking NSAIDs than when using colchicine and GC both after 3 (63%) and 6 (81%) months (p< 0.05 in both cases). After 3 months of observation, the intensity of pain according to the VAS during the development of a gout attack was less for NSAIDs therapy than for colchicine and GC (p< 0.05 in both cases), and after 6 months there was no difference between NSAIDs, colchicine and GC. Within first 3 months, there was no difference in the duration of arthritis attacks among anti-inflammatory drugs, whereas after 6 months duration of attacks was the smallest for NSAID therapy (p< 0.05). Adverse reactions occurred only in NSAID and colchicine therapy in 2 and 5 patients, respectively. The patient's refusal to continue therapy without cause occurred in 13 (15%) cases, more often when taking colchicine.

Conclusion. The proposed algorithm of anti-inflammatory drugs prescription for prevention of arthritis recurrence can reduce the risk of gout attacks development with good tolerance of the therapy. At the same time, better control of the frequency and duration of arthritis attacks, as well as the intensity of pain according to the VAS, is observed with the use of NSAIDs than with the use of colchicine and GC.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to control pain in rheumatoid arthritis (RA). However, many aspects of the therapeutic effect of NSAIDs in RA have not been sufficiently studied. In particular, this concerns the effect of NSAIDs on the inflammatory activity of the disease.

Objective: to study the comparative efficacy and safety of NSAIDs in RA patients with moderate and low disease activity.

Patients and methods. The study group consisted of 404 patients with RA, 69% women and 31% men, mean age 58.6±10.0 years, with moderate and low disease activity – DAS28<5.1 (mean value 3.7±1.5), who initially had moderate or severe pain: >4 cm on the visual analog scale (VAS) 0–10 cm. All patients received DMARDs, mostly methotrexate 15 to 25 mg weekly, 8.2% biological agents, 18.6% glucocorticoids. All patients were prescribed NSAIDs at the full therapeutic dose. The results of treatment were evaluated after 2 weeks, 1, 3 and 6 months. Criteria of efficacy were the dynamics of pain (10 cm VAS), Patient Global Health (PGH on a 10-cm VAS), the change in the tender joints count (TJC) and swollen joints count(SJC), and dynamics of RA activity (DAS28).

Results and discussion. 54.2% of patients received aceclofenac, 19.8% nimesulide, 14.3% meloxicam, 9.1% diclofenac, 2.6% – other NSAIDs. After 2 weeks, the pain decreased from 6.3±1.2 cm to 4.5±1.5 cm on VAS (p<0.001). The severity of pain continued to decrease further, and after 6 months of observation was 4.0±1.2 (p< 001, compared with the baseline level). A similar result was observed for the TJC, SJC, and PGH: the dynamics of these indicators, in comparison with the baseline level, was statistically significant after 2 weeks and after 1, 3, and 6 months of observation (p< 0.05). There was a decrease in the disease activity by DAS28: from 3.7±1.5 to 3.4±1.1 after 3 months (p=0.041) and 3.1±0.9 after 6 months (p=0.02). The effectiveness of aceclofenac and other NSAIDs for pain reduction, TJC, SJC, PGH and DAS28 did not differ. The tolerability of aceclofenac was better than of other NSAIDs: the frequency of dyspepsia after 2 weeks was 23.3% and 36.2% (p=0.004). The frequency of arterial hypertension and edema in patients who used aceclofenac, after 2 weeks and 6 months was slightly lower than in patients treated with other NSAIDs, but the difference was not statistically significant.

Conclusion. The use of NSAIDs can effectively control the pain and other symptoms of RA, as well as the disease activity by DAS28 in patients with moderate or low disease activity. Aceclofenac is not inferior to other NSAIDs in analgesic potential and exceeds them in tolerability.

The group of scleroderma diseases includes a number of clinical entities, the main symptom of which is skin tightening. Scleroderma is a prominent example of these diseases, characterized by excessive synthesis and deposition of collagen in organs and tissues. A patient with juvenile systemic scleroderma with induration of the skin and underlying tissues, and persistent contractures of large joints since childhood, is described. This clinical example illustrates disease course peculiarities and differential diagnosis of systemic and limited (focal) scleroderma and scleroderma-like conditions in pediatric patients. The feasibility of pathogenetic therapy aimed at improving patient's the quality of life with formed disease phenotype is shown.

The article provides a description of the systemic lupus erythematosus patient with multiple avascular bone necrosis (ABN), homozygous mutation in clotting factor V (Leiden) gene, who successfully underwent the total hip replacement. The role of high doses of glucocorticoids and coagulation disorders, in particular the homozygous mutation in factor V (Leiden) gene, in the development of ABN is discussed.

Difficulties in diagnosis and therapy of scleroderma-panniculitis (S-PN), one of the variants of the septal PN, are discussed. Feasibility of ultrasonography, magnetic resonance imaging of soft tissues and histological examination of the lesions in order to set the diagnosis of PN in time is considered. The clinical case of S-PN combined with antiphospholipid syndrome is presented.

Updated ACR recommendations for the treatment of gout concerning lifestyle are discussed. Factors related to a lifestyle, above all food habits, for many years were of leading importance in the treatment of patients with gout, even after application of effective drugs. The authors of the updated ACR recommendations for the first time offered to reconsider the role of environmental factors in the genesis of gout and objectively assess the possibility of its non-drug treatment. On the one hand, regardless of the activity of the disease, the need for restrictions of the alcohol, purine-rich products and fructose-containing beverages, as well as the decrease of body weight in obese patients and vitamin C usage unviability are confirmed. On the other hand, these recommendations are conditional. Their new version of ACR recommendations is significantly different from both its previous version and other international and national recommendations, including recommendations on the diagnosis and treatment of gout used in the Russian Federation.

The review highlights the problem of finding new effective treatment strategies for COVID-19. Tumor necrosis factor α (TNF-α) is considered as a therapeutic target. The theoretical basis for the successful use of TNF-α inhibitors (ITNFα) for the treatment of COVID-19 is presented, as well as data on existing practical developments, including ongoing clinical trials. Two drugs from the group of ITNFα – infliximab and adalimumab – are currently being considered as possible options. The safety issues of ITNFα treatment in patients with immunophaling rheumatic diseases and COVID-19 are discussed. The review also provides current data on vaccination against COVID-19, in particular on the vaccines currently available in Russia, which are at different stages of clinical trials. We conclude that randomized clinical trials of the effectiveness and safety of ITNF-α in patients with the new coronavirus infection are needed. Such trials will promote transition from theoretical speculations to real clinical practice.

Well-established and some little-known treatments of axial spondyloarthritis / ankylosing spondylitis (AS), which have appeared in recent years are discussed, also discussed are emerging trends for AS treatment.

In recent years, highly effective target drugs – inhibitors of interleukin 17A (iIL17A) – monoclonal antibodies, – have been widely used to treat patients with psoriatic arthritis (PsA). The efficacy of iIL-17A in psoriasis, PsA, and axial spondyloarthritis has been proven in large multicenter randomized clinical and observational studies. The accumulated evidence and first direct comparative studies with inhibitors of tumor necrosis factor α (iTNFα) suggest that this class of drugs is becoming one of the key drugs in PsA, and the choice of this therapy is more justified, which is reflected in international recommendations. The 2019 revised EULAR guidelines consider iIL 17 first-line biologics along with iTNF-α, whereas iIL-17A is a drug of choice in patients with significant concomitant skin psoriasis.

The article highlights the current status of symptomatic slow-acting drugs (SYSADOA) in osteoarthritis (OA). Mechanism of action, clinical studies data on the effectiveness of glucosamine (GA) and chondroitin sulfate (CS) and their combinations in OA, their positive symptomatic and structural-modifying effects, are described. The article provides the latest recommendations for the OA treatment with these two drugs and presents an argument for the combination therapy with both drugs as a background therapy in the earliest stages of OA. It is indicated that such therapy should be long-term due to its high safety and possible reduction of cardiovascular accidents risk as well. It is noted that therapeutic doses of CS and GA are ≥1500 and ≥800 mg per day, respectively, and encapsulated forms of SYSADOAs have advantages due to their pharmacokinetic features.

The article presents current data on synovitis (inflammation of the synovial membrane), which is often the only clinical manifestation of osteoarthritis (OA), and considered to be one of the risk factors for the OA development. Synovitis severity correlates with the severity of OA symptoms. The assessment of the prevalence of synovitis presents significant difficulties and depends on the nature and severity of the disease, the cohort in question, diagnostic method, and therapy. The classification based on etiological, clinical and histological characteristics of synovitis is presented. Examination of synovial tissue characteristics and its changes during inflammatory response can significantly expand the possibilities for therapy and prognosis. The use of symptomatic delayed-action drugs (SYSADOA) is considered as the basic treatment of OA. Chondroitin sulfate (Chondroquard®) is one of the well established drugs, it has symptom- and structural-modifying properties. The article presents the results of studies confirming its effectiveness in reducing the severity of knee synovitis.

The effectiveness of combined drugs, consisting of chondroitin and glucosamine (GA) in the treatment of osteoarthritis (OA) is discussed. Due to their high safety and pleiotropic effects, these drugs can be used in patients with OA (primarily with metabolic and inflammatory phenotypes) and comorbid diseases. The effect of oral chondroitin and GA on the intestinal microbiota is described: regulation of the composition, metabolic and immunological activity of intestinal microbiota. The relationship between the regular administration of chondroitin and GA and decrease in overall mortality and mortality from cardiovascular diseases, as well as the decrease of malignancy development risk is marked.