Systemic lupus erythematosus (SLE) is a systemic autoimmune rheumatic disease of unknown etiology, characterized by the overproduction of organ-specific autoantibodies to various components of the cell nucleus and by the development of immune-mediated inflammatory damage to internal organs. SLE is the prototype of a systemic human autoimmune disease; it is an extremely heterogeneous disease in terms of both clinical manifestations and a genetic predisposition and pathogenetic mechanisms, which often complicates the early diagnosis of the diseases and makes it impossible to personify therapy. Despite the fact that in the 21st century, the 15-year survival rate for SLE has increased up to 85%, the inadequate control of disease activity and the need for almost constant intake of glucocorticoids and immunosuppressive drugs result in the accrual of irreversible damages to internal organs and, as a consequence, in decreases in quality of life, disability, social maladaptation, and premature death. The paper considers the new 2019 EULAR/ACR diagnostic criteria for SLE, the contemporary 2019 EULAR recommendations for the management of SLE, and new pharmacotherapy options for this condition, which are based on the deciphering of the mechanisms of SLE immunopathogenesis.

Erosive osteoarthritis (EOA) of the hand is an osteoarthritis (OA) phenotype that is characterized by central and marginal erosions of the articular surfaces in the distal and proximal interphalangeal (DIP and PIP) joints and in some cases by a fairly aggressive course with obvious pain syndrome and a high level of functional impairment. Diagnostic criteria and management tactics for EOA patients are still under investigation.

Objective: to evaluate the nature of the changes detected by hand joint magnetic resonance imaging (MRI) in patients with EOA and non-erosive OA (NEOA) of the hand.

Subjects and methods. Examinations were made in 61 females meeting the American College of Rheumatology (ACR) diagnostic criteria for hand OA; the patients' mean age was 66.34+5.79 years; the median age at disease onset was 50 [45; 56] years; the duration of pain was 15 [11; 20] years. All the patients underwent MRI of the second-fifth DIP, PIP, and metacarpophalangeal (MCP) joints of the right hand. The patients also filled out the AUSCAN questionnaire. EOA and NEOA were detected in 30 and 31 patients, respectively.

Results and discussion. The patients with EOA and those with NEOA were matched for gender, age, and disease duration. The DIP joints in patients with EOA were found to have significantly more frequently and a greater number of large osteophytes (OPs), (53 and 16%, respectively), joint space narrowing (JSN) (73 and 35%), degenerative collateral ligament changes (DCLCs) (93 and 55%), subluxations (47 and 13%), and bone marrow edema (BME) (57 and 19%) than in those with NEOA. Synovitides and subchondral cysts occurred with approximately the same frequency in EOA and NEOA. The PIP joints in patients with EOA significantly more frequently showed BME (37%) and DCLCs (97%) than in those with NEOA. Subluxations in the PIP joint of the right hand were encountered exclusively in patients with EOA. Their incidence was 17%. Degenerative symptoms (small, less often moderate sizes of OPs, JSN, and DCLCs) were identified with approximately the same frequency in both groups (p>0.05). The PIP joints in patients with EOA were significantly more often found to have BME (53 and 26%, respectively; (p<0.05), cortical defects (CDs) of the metacarpal head (73 and 45%) than in those with NEOA. The incidence of subchondral cysts, OPs, JSN, and DCLCs was not significantly different in both groups (p>0.05). Large OPs in the PIP joint were found relatively rarely. Subluxations in the PIP joints were undetected in both groups.

Conclusion. The symptoms of active inflammation are predominant and degenerative changes are more pronounced in patients with EOA unlike those with NEOA. Articular surface defects in the PIP joints in patients with hand OA differ from erosions in those with rheumatoid arthritis. These CDs in EOA are much more common than those in NEOA; however, the nature of their occurrence is unclear; therefore, the patients in whom they have been found need dynamic monitoring.

Kidney involvement is one of the extraarticular manifestations of ankylosing spondylitis (AS). Due to a number of disadvantages of traditional parameters for evaluating renal function, an active search is underway for new markers.

Objective: to evaluate urinary excretion of liver-type and heart-type fatty acid-binding proteins (L-FABP and H-FABP) in patients with AS.

Subjects and methods. Urine samples were examined in 50 patients (37 men and 13 women) at least 18 years of age with a reliable diagnosis of AS without secondary nephropathy (with the exception of AS-associated changes). The median age of the patients was 39 [34; 56] years; the duration of AS was 10 [7; 18] years. L-FABP and H-FABP levels were measured by enzyme-linked immunosorbent assay. The values obtained were given for urinary creatinine excretion. The results were compared with those of the gender- and age-matched control group.

Results and discussion. L-FABP excretion in patients with AS without chronic kidney disease (CKD) was significantly higher than that in the control group: 0.05 [0.01; 0.09] and 0.03 [0; 0.06] ng/mmol of creatinine, respectively (p=0.04). Only 6 patients were found to have H-FABP excretion and its level did not exceed 601.5 ng/mmol of creatinine. In healthy volunteers, the excretion of H-FABP was below the detection range. The level of FABPs did not depend on age, glomerular filtration rate (GFR), or disease activity. The level of H-FABP correlated with albuminuria (rs=0.49; p<0.05). L-FABP and H-FABP concentrations were weakly correlated with each other (rs=0.24; p<0.05).

Conclusion. Urinary excretion levels of L-FABP and H-FABP are higher in patients with AS than those in healthy individuals. The found correlations may indicate the excretion of these FABPs at different stages of kidney involvement and thus be of interest for assessing the level and stage of tubulopathy in patients with AS.

Objective: to assess whether the modified combined glucocorticoid (GC) toxicity index (MCGTI) can be used to analyze adverse reactions (ARs) to GCs administered in the management of rheumatoid arthritis (RA).

Subjects and methods. The investigation enrolled 71 RA patients (57 females, 14 males; mean age, 51.7+15.2 years). All the patients met the ACR/EULAR classification criteria and took GCs (the median duration of GC treatment duration was 7.1 [0.9; 12.0] years). In addition to the standard clinical, laboratory, and instrumental indicators, the daily and cumulative doses of GCs (in prednisolone equivalent) and MCGTI were analyzed.

Results and discussion. The value of MCGTI statistically significantly correlated with treatment duration (r=0.411), age (r=0.384), and the cumulative dose of GCs (r=0.361), but did not correlate with their maximum dose (r=0.06). A ROC analysis showed that the critical level of the cumulative dose of GCs in relation to MCGTI was 17,337.5 mg.

Conclusion. MCGTI correlates with cumulative dose (making it possible to establish its critical level), treatment duration, and age, which is the basis for further study of whether this can be applied in clinical practice to evaluate, predict, and prevent ARs.

A wide range of biological agents recently introduced into clinical rheumatology determines a special interest in their tolerance. The paper presents the authors’ own data, as well as a review of foreign literature on this issue.

Objective: to analyze the tolerability of infliximab (INF) in patients with rheumatoid arthritis (RA) in real clinical practice

Subjects and methods. The analysis included 135 RA patients receiving INF alone or in combination with diseasemodifying antirheumatic drugs.

Results and discussion. The total tolerance of INF was satisfactory. Adverse reactions (ARs) were noted in 28.1% of cases, including in 19 (14.1%) patients who had serious ARs that required drug discontinuation.

Conclusion. The best tolerance was observed with a combination of INF and methotrexate. The authors draw attention to the need for medical examination prior to each drug administration.

Family Mediterranean fever (FMF), or a periodic disease, is the most common hereditary disease among Armenians. FMF manifests mainly in childhood, presenting a significant problem for the pediatric health care system in Armenia. The clinical presentations of FMF have much in common with that of vasculitides: fever, abdominal pains, arthritis, myalgias, and skin damage. The data available in the literature indicate the high incidence of vasculitides in patients with FMF in the ethnically significant groups compared with the general population.

Objective: to investigate the clinical and genetic characteristics of FMF-associated vasculitides in children of Armenia. Subjects and methods. The National Pediatric FMF Center, Arabkir Medical Complex, Institute of Child and Adolescent Health, examined a group of 715 children (438 boys, 277 girls; mean age, 8.64+0.17 years) with FMF. The diagnosis of FMF was confirmed using the Tel-Hashomer criteria and the MEFV gene mutation analysis. The Epi-Info 2000 program was used for statistical analysis.

Results and discussion. The rate of vasculitides was 4.3% (n=31), being generally higher than expected. In particular, the diagnoses made were Henoch-Scho nlein pirpura (HSP) in 11 (1.5%) children, protracted febrile myalgia (PFM) in 20 (2.7%), and Behcet’s disease (BD) in 1 (0.1%) patient. The patients were characterized by early-onset FMF (at an average of 3 years) with a moderate/severe course, frequent episodes, a predominance of articular syndrome, more commonly acute relapsing arthritis, with the addition of clinical presentations of vasculitis on average 5—6 years after the onset of FMF, and genetically by the M694V homozygous genotype (M694V/M694V). HSP and PFM were observed in 2.9 and 4.6% of patients with the M694V homozygous genotype, respectively (p<0.02).

Conclusion. The rate of FMF-associated vasculitides in the children of Armenia was 4.3%: HSP, PFM, and BD were diagnosed in 1.5, 2.7, and 0.1% of patients, respectively. The findings allow HSP and PFM to be considered as additional markers for the severe course of FMF and the M694V homozygous genotype as a risk factor for PFM. They also indicate the feasibility of the MEFV gene mutation screening in children with vasculitides in Armenia for an association with FMF for early diagnosis of the disease, timely administration of colchicine, and prevention of complications.

Objective: to estimate the changes of the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI) over a five-year period in patients with systemic sclerosis (SS) according to the clinical type of the disease and the use of low doses of glucocorticoids (GCs), methotrexate (MTX), and hydroxychloroquine (HCQ).

Subjects and methods. The data of a clinical observation in 68 patients with SSD were analyzed, by estimating the SCTC-DI at two time points: May-July 2019 and retrospectively in 2014. The changes of the index values were studied in the observed patients according to the SS type (diffuse, n=15 and limited, n=46) and treatment (low doses of GCs, n=29, MT, n=18 and HCQ, n=16) used for at least 36 months within 5 years.

Results and discussion. The observed patients with SS over a five-year period showed increases in the average SCTC-DI from 3.91 to 6.73 and in the number of patients with SCTC-DI >1 from 76.4 to 88.2%. The increase in SCTC-DI in diffuse SS was more significant than in limited SS (its median was 5.10 [4.34; 6.35] and 2.19 [1.84; 3.06], respectively; p<0.05). Analysis of SCTC-DI dynamics established that in patients treated with MTX, the increase in the score for musculoskeletal system damage was less than in those untreated with this drug (its median was 0.24 [0.11; 0.33] and 0.63 [0.41; 0.75], respectively; p<0.05). The increase in the score for cardiovascular system damage during GC treatment was less significant than without this therapy (0.12 [0.05; 0.27] and 0.47 [0.31; 0.56], respectively; p<0.05). In patients receiving low-dose GCs, the increase in the score for gastrointestinal tract damage was more significant than without such therapy (1.02 [0.87; 1.21] and 0.73 [0.51; 0.83], respectively; p<0.05).

Conclusion. The investigation demonstrated an increase in the values of all components of the SCTC-DI for damage to various organs and systems in SS over a five-year period. The SCTC-DI is a promising tool for evaluating the impact of ongoing therapy on the development of irreversible damage to the target organs of the SS disease process.

Various clinical and immunological phenotypes of systemic sclerosis (SS) differ in the frequency and severity of manifestations of the disease, the progression of damage to internal organs, and prognosis. The detection rate of anti-U1-ribonucleoprotein (RNP) (anti-U1RNP) antibodies in SSD ranges from 5 to 30%. They are found in various rheumatic diseases (SS, systemic lupus erythematosus, rheumatoid arthritis, polymyositis, and Sjo gren’s syndrome) and are associated with a more favorable course, a good response to treatment (in particular, that with glucocorticoids), and a good prognosis. In SS, the clinical and laboratory associations of anti-U1RNP have been insufficiently investigated.

Objective: to compare clinical, laboratory, and instrumental findings in patients with SS positive for anti-U1RNP, anti-topoisomerase-I (anti-Scl70), and anticentromere antibodies (ACA).

Subjects and methods. Sixty-five anti-U1RNP antibody-positive patients were selected for a study group (Group 1) from the general database of patients who met the 2013 ACR/EULAR criteria for SS and who were followed up at the V.A. Nasonova Research Institute of Rheumatology in 2012 to 2017. The comparison groups included 50 anti-Scl70 antibody-positive patients with SS (Group 2) and 50 ACA-positive ones (Group 3). Anti-U1RNP negativity was confirmed in patients of the comparison groups.

Results and discussion. Most patients in Groups 1 and 3 had the limited type of SS (88 and 94%, respectively) and a chronic course of the disease (82 and 94%) while Group 2 patients showed an acute and subacute course (52%) and predominantly the diffuse type of SS (58%). All the patients with SS had a higher level of antinuclear factor. The feature of the anti-U1RNP positive group was a preponderance of the limited type of the disease with minimal skin damage concurrent with a more frequent involvement of the musculoskeletal system (damages to the joints (65%) and muscles (43%), as well as with the high rate of damage to internal organs (in particular, the lung, heart, and gastrointestinal tract). The patients of this group exhibited high inflammatory and immunological activities, hematological disorders (hypocomplementemia (15%) and leukopenia (14%)). Sjo gren’s syndrome was detected in one-third of these patients.

Conclusion. Further study of anti-U1RNP-positive SS will be able to create a management algorithm and to more clearly define the risks and prognosis of the disease for this group of patients.

Magnet therapy (Mt) is a well-known physiotherapy technique that is widely used to treat knee osteoarthritis (OA). Objective: to determine the efficiency and safety of Mt for knee OA.

Subjects and methods. A study group consisted of 231 patients with knee OA (77.9% were women; mean age,

61.9+12.2 years; body mass index, 30.6+5.8 kg/m2; median disease duration, 5.0 [2, 0; 10.0] years). The patients were randomly assigned to two groups. Group 1 patients received Mt with an ALMAG+ device for 14 days; Group 2 had false Mt with a completely imitating ALMAG+ device that failed to create a magnetic field. The investigators evaluated the changes of the WOMAC index, pain intensity at rest and during movement on a 100 mm visual analogue scale (VAS), the need for nonsteroidal anti-inflammatory drugs (NSAIDs), and the degree of improvement, as assessed by patients (on a 5-point scale).

Results and discussion. During the therapy, there was a statistically significant pain and stiffness reduction and functional improvement. Thus, there were decreases in the median WOMAC pain scores from 231 [180; 290] to 110 [60; 166.3] (p<0.001) in Group 1, from 212.4 [145; 260] to 143 [76.5; 200] (p<0.001) in Group 2, in pain intensity at rest from 47 [27.8; 60] to 20 [10; 30] mm (p<0.001) in Group 1; from 40 [20; 57.5] to 20 [7.5; 40] mm (p<0.001) in Group 2. During the therapy, there was also a reduction in the need for NSAIDs: the drug was discontinued or its dose reduced in 33.1% and 16.8% of the patients in Groups 1 and 2, respectively (p=0.006). The changes of all parameters were statistically more significant in Group 1 than in Group 2. Treatment results were assessed as good and excellent by 58.5% and 39.8% patients in Groups 1 and 2, respectively (p<0.001). No serious adverse events to true and false Mt were observed. Therapy was discontinued due to increase of joint pain in two patients who received false Mt.

Conclusion. Short-term Mt provides a significant improvement in patients with knee OA. Mt is well tolerated and causes no serious complications.

Deciphering the mechanisms of the pathogenesis of immune-mediated inflammatory rheumatic diseases (IIRDs) and designing a wide range of biological agents (BAs) are the major achievements of 21^st century medicine. A new promising area of pharmacotherapy for IIRDs is associated with the design of so-called targeted oral medications that primarily include Janus kinase (JAK) inhibitors, called jakinibs. The first representative of the class of JAK inhibitors is tofacitinib (TOFA), which has been registered for the treatment of rheumatoid arthritis (RA), psoriatic arthritis, and ulcerative colitis. The review (Part I) presents new data on the efficacy and safety of TOFA in RA and discusses the role of TOFA in the treatment of RA as part of the treat-to-target strategy and new EULAR recommendations. Part II of the review will provide data on the use of TOFA in other IIRDs.

Calcium pyrophosphate crystal deposition disease (CPPD) is an inflammatory joint disease associated with abnormal accumulation of inorganic pyrophosphate. CPPD is frequently associated with metabolic disorders, such as hyperparathyroidism, hemochromatosis, hypomagnesemia, and hyperphosphatasia. It is important that pathological calcification can develop in both the joints and vessel wall. It is assumed that the deposition of calcifications in the endothelium, the crystal-induced chronic inflammation characteristic of CPPD, and its accompanying oxidative stress, as well as metabolic disorders that are a cause of secondary CPPD, can significantly increase the risk of cardiovascular diseases.

Functional dyspepsia (FD) is one of the dysregulatory lesions of the upper digestive tract. This syndrome has fairly well-defined clinical manifestations that include borderline psychopathological disorders. Its diagnosis becomes a method for ruling out organic gastrointestinal and mental illnesses. Treatment for FD is complex and includes a behavioral component, prokinetics, myotropic spasmolytics, antisecretory drugs, and tricyclic antidepressants. The efficiency of therapy directly depends on a physician's ability to choose an individualized regimen.

The glycosaminoglycan-peptide complex (GPC) Rumalon is a popular injectable drug used to treat osteoarthritis (OA). GPC was one of the world’s first drugs designed for the pharmacotherapy of this disease. The drug has been rigorously tested for efficacy and safety in a series of international placebo-controlled randomized trials. Most of them showed the good therapeutic potential of GPC. Several open-labelled studies have recently been underway in Russia, confirming the ability of GPC to significantly reduce the intensity of pain and to improve function in patients with knee OA and chronic nonspecific back pain. All investigations of GPC demonstrated its good tolerance and the absence of serious complications, as well as when this medication was used for a long time.

Currently, there are a lot of different surgical treatments for hallux rigidus, such as cheilectomy; first metatarsal osteotomies, hemiarthroplasty, arthroplastry and arthrodesis of the first metatarsophalangeal joint (MTPJ), and all of them have both advantages and disadvantages. To date, there is no single approach to choosing a method of surgical treatment of hallux rigidus. The autologous matrix-induced chondrogenesis (AMIC) technique is known to be quite successfully used for the treatment of osteochondral defects in the knee, hip, and ankle joints.

Objective: to study the immediate results of first MTPJ chondroplasty using the AMIC technique in patients with hallux rigidus.

Subjects and methods. As of now, MTPJ chondroplasty using the AMIC technique has been performed at the Nasonova Research Institute of Rheumatology in the first 9 patients with hallux rigidus. The surgery was made on both sides in one patient; there were accordingly a total of 10 above operations. The patients' mean age was 42.2+19.5 (range 20—71) years. During the examination, the investigators determined the range of motion in the first MTPJ, the intensity of pain on a visual analogue scale (VAS); foot status according to the American Orthopedic Foot and Ankle Society (AOFAS) scale; as well as the foot function index (FFI) and the functional condition of the foot and ankle (FA) joints according to VAS-FA. Prior to surgery, all the patients experienced significantly restricted motions in the first MTPJ. The median range of motion in the first MTPJ was 20°; Pain intensity was 70 mm; the AOFAS score was 52; FFI — 6.4; the VAS-FA — 4.1. First MTPJ chondroplasty was performed according to the AMIC technique using the Chondro-Gide and Aesculap Novocart Basic collagen matrices. The results of surgical treatment were assessed at 3, 6, and 12 months postoperatively.

Results and discussion. Just 3 months after surgery, there was a pronounced significant reduction in first MTPJ pain. Its median decreased from 70 to 27.5         mm. After 6 months, there were also positive changes; the median pain was 10 mm. It remained at a level of 10 mm by the end of the first year of the observation. The median AOFAS scores increased from 52 to 78.5 and 90 at 3 and 6 months after surgery, respectively, and remained at the same level at 12 months. The median FFI decreased from 6.4 to 2.3, 1.1, and 0.8 at 3, 6, and 12 months following chondroplasty, respectively. The median VAS-FA scores were 8.1, 9.3, and 9.6 at 3, 6, and 12 months after chondroplasty. At 3 months postoperatively, the range of first MTPJ motion also increased significantly: its median rose from 20° to 60°; it was 65° at 6 months and increased to 67.5° at 12 months. First MTPJ chondroplasty with the AMIC technique in these patients resulted in positive changes that were maximal at 3 months after the surgery: the median pain decreased by 42.5      mm; AOFAS, FFI, and VAS-FA scores increased by 26.5, 2.1, and 4.0, respectively. Of great importance is also the increase in first MTPJ motion range, the median of which rose by 40° at 3 moths. The positive changes also persisted 6 months postoperatively. During this period, there was a further decrease in the median pain by 17.5 mm and increases in the median AOFAS, FFI, and VAS-FA scores by 12.5, 1.2, and 1.2, respectively. At 12 months of the follow up, the achieved improvement remained; however, the number of observations at this stage does not allow for adequate statistical analysis.

Conclusion. The immediate results of the performed operations showed that first MTPJ chondroplasty using a collagen matrix can be a rather effective surgical treatment that makes it possible to relieve pain and to significantly improve quality of life in patients with hallux rigidus. A more complete evaluation of the efficiency of first MTPJ chondroplasty using the AMIC technique will be provided by studying the medium-term and long-term outcomes of the surgery.

Objective: to assess the long-term results of medical treatment for lower extremity stress fractures.

Subjects and methods. Fifty-five patients who had received a medical treatment cycle in the European Clinic of Sports Traumatology and Orthopedics (ECSTO) in the period 2010 to 2016 were followed up. The patients' mean age was 37 (range 15—65) years. Among them, there were 36 (65%) females and 19 (35%) males. The long-term results of treatment were assessed using the Foot and Ankle Ability Measure (FAAM) scale (ADL + sport modules) and the Lower Extremity Functional Scale (LEFS) scales.

Results and discussion. Assessing the degree of stress adjustment according to magnetic resonance imaging (MRI), on visiting, in accordance with the classification proposed by E.A. Arendt et al., revealed grades 2, 3, and 4 injuries in 10 (18%), 14 (26%), and 16 (29%) patients, respectively. The median time from the moment of visiting before assessment according to the orthopedic scales was 3 years (1 to 7 years). The second and third metatarsals underwent stress adjustment in 25 (47%) patients. The cause of stress adjustment was most often running (38%), less often walking (29%), playing sports (18%), fitness (9%), and other types of physical activity (6%). Assessing the scores for the FAAM ADL and FAAM sport subscales showed that the median was 100 [96; 100]% and 100 [91; 100]%, respectively. Estimating the scores for the LEFS scale revealed excellent, good, and satisfactory results in 48 (87%), 6 (11%), and in 1 (2%) patients, respectively.

Conclusion. The most common cause of lower extremity stress fractures is running. These changes respond well to medical treatment, which includes injured limb overuse, physiotherapy, and individual ankle-foot orthosis.

The paper describes two patients with systemic lupus erythematosus (SLE) with severe nervous system damage characterized by diffuse and focal neuropsychiatric manifestations of SLE due to of the central nervous system involvement and damage to the peripheral nervous system as local mononeuritis of the lower extremities in one case and severe peripheral neuropathy manifested by multiple mononeuritis of the lower extremities in the other. Anti-B cell therapy with rituximab is noted to have an effect.

The paper provides the updated American College of Rheumatology (ACR) guidelines for the treatment of ankylosing spondylitis and non-radiographic axial spondyloarthritis.