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Rheumatology Science and Practice

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Vol 58, No 2 (2020)
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FRONTIERS

123-132 5404
Abstract
In December 2019, an outbreak of a novel infection under the working name 2019-nCoV was registered in Wuhan (the Hubei Province located in China’s central region), which has quickly spread throughout almost the entire world and become pandemic. The World Health Organization (WHO) proposed a new name coronavirus disease (COVID-19) for this disease, whereas the International Committee on Virus Taxonomy renamed 2019-nCov as SARS-Cov-2 (Severe Acute Respiratory Syndrome Coronavirus-2). The development of the COVID-19 pandemic is not only of great social importance, but also draws the attention of a medical community to the fundamentally new clinical and fundamental problems of the immunopathology of human diseases that are yet to be formulated. The unique experience gained in rheumatology from studies of the pathogenetic mechanisms and pharmacotherapy of immune-mediated inflammatory rheumatic diseases (IMIRDs) can be of great importance for deciphering the nature of the pathological processes that underlie the severe, potentially fatal complications of COVID-19, and may assist in improving their therapy. As for prospects in patients with IMIRDs, although the development of COVID-19 in the presence of IMIRDs has not yet fortunately been described, infection with SARS-CoV-2, like other viruses, can be assumed to cause an exacerbation of the pathological process, whereas severe immune system pathology and comorbidities can worsen the course of infection. Since, according to the
current concepts, it is the «hyperimmune» response, and not just the effect only of the virus itself, that underlies lung damage and deaths from COVID-19, special attention is drawn to the effects of antirheumatic therapy that includes glucocorticoids, disease-modifying anti-rheumatic drugs (DMARDs), biological agents, and targeted DMARDs, which can have a multidirectional effect on the course of COVID-19. There are significant theoretical prerequisites for the repurposing of some drugs widely used in rheumatology for the treatment of COVID-19 and its complications. Consideration is given to the prospects of studying the immunopathology of COVID-19 and to the theoretical justifications for the use of antimalarial 4-aminoquinolines, anti-cytokine monoclonal antibodies (mAbs), and Janus kinase inhibitors for the prevention of complications and for the treatment of COVID-19.

INTERNATIONAL AND RUSSIAN GUIDELINES FOR THE TREATMENT OF RHEUMATIC DISEASES

133-139 752
Abstract
These clinical guidelines have been developed under the auspices of the All-Russian public organization «The Association of Rheumatologists of Russia» and the public organization «Russian Osteoporosis Association» and are dedicated to the diagnosis of the risk of falls and their prevention in elderly people who have a high frequency of falls and their serious consequences as injuries varying in severity, as fractures, developed pain, a loss of ability to perform everyday activities and to take care of themselves. The paper presents risk factors for falls and risk assessment methods and formulates main provisions for preventing falls in older people, by taking into account their place of stay: at home, hospital or social services facilities.

ORIGINAL RESEARCH

140-146 760
Abstract
The paper presents three cohorts of patients with early rheumatoid arthritis (RA) who fell ill at 50 years or older and had a disease duration of 1.5 months to 1 year. To establish its diagnosis, the investigators used classification criteria for each cohort of its period: 1) the 1958 American Rheumatism Association (ARA) criteria; 2) the 1987 ARA criteria, and 3) the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria. Along with a change in the criteria, diagnostic methods were improved in this period. Many qualitative laboratory parameters were replaced with their quantitative equivalent; new disease markers (including anti-cyclic citrullinated peptide antibodies) emerged; imaging methods were improved; treatment policies were changed, and targeted biological agents and numerous analogs of the original drugs appeared.
Conflicting opinions about the course of RA in older age groups have repeatedly been published in the literature. In the period when the 1958 classification criteria were applied, the opinion that RA has a relatively favorable course was prevalent. Later on, when a more rigid approach to diagnosing RA was applied, there were more and more specialists who considered it to be a severe disease. In this study, the authors try to answer the question of whether the course of the disease changed in the older age groups at the earliest possible date after its onset, by comparing the three cohorts of patients. The findings are discussed.

147-153 709
Abstract

The prevalence of sarcopenia in different countries of the world has been well studied. However, the criteria of different international professional groups are used to diagnose the disease, which leads to large variability in data on the frequency of sarcopenia in the population. The paper presents the results of studying the frequency of sarcopenia, by using the diagnostic criteria of different working groups. The measures characterizing muscle strength and skeletal muscle function were analyzed; the components that are most important for the diagnosis of sarcopenia were identified in the studied patient group.

Objective: to determine the detection rates of sarcopenia among people aged over 65 years in accordance with the guidelines of different international professional groups and to identify the most significant component for its diagnosis.

Subjects and methods. The investigation enrolled 230 people older than 65 years (mean age, 74.0±6.5 years) who were followed up in an outpatient setting. Sarcopenia was diagnosed according to the 2010 European Working Group on Sarcopenia in Older People (EWGSOP) criteria. To confirm its diagnosis, the appendicular muscle mass index (AMMI) was calculated using dual-energy X-ray absorptiometry (DXA) on a HOLOGIC QDR Explorer; muscle strength was measured with a Jamar-J00105 handheld dynamometer (Sammons Preston Inc., USA). Muscle function was also examined using the short physical performance battery (SPPB). The frequency of sarcopenia diagnosed by the criteria of the International Working Group on Sarcopenia (IWGS), the Foundation for the National Institutes of
Health (FNIH), and EWGSOP were comparatively analyzed.

Results and discussion. The frequency of sarcopenia in the sample of people aged over 65 years was the same when using the diagnostic EWGSOP and IWGS criteria (30%) and was significantly higher than when applying the FNIN criteria (19.8%). The frequency of sarcopenia increased from 21.4% at the age of 65–74 years to 52.9% at the age of over 85 years according to the EWGSOP and IWGS criteria and from 16.2% to 29.4%, respectively, by the FNIN criteria. Dynamometry showed that the muscle strength was significantly lower in patients with low muscle mass than in those with normal muscle mass (the average mass was 15.1±5.4 and 18.2±5.4 kg, respectively; p<0.001) among both males and females. The average SPPB scores in the entire sample were low in all the studied groups (7.6±3.1). It was significantly lower in patients with low muscle mass than in people with normal muscle mass (6.9 and 7.9 scores, respectively; p=0.016) as shown mainly by the Tandem test (p=0.0002). No substantial differences in the frequency of sarcopenia were found in different age groups according to the EWGSOP and EWGSOP2 criteria.

Conclusion. The frequency of sarcopenia among people aged over 65 years according to the criteria adopted by professional communities varied widely from 19.8% (FNIN) to 26.5% (EWGSOP2) and 30% (EWGSOP). With age, the frequency of sarcopenia increased, reaching 52.9% among people over 85 years of age. Muscle strength measurement versus other functional tests is a more sensitive diagnostic method for sarcopenia.

154-159 20073
Abstract

There has been an increase in the survival rates of patients with systemic lupus erythematosus (SLE) in recent decades.

Objective: to determine the survival rates of SLE patients in the Republic of Tatarstan.

Subjects and methods. The records of SLE inpatients treated at the Nephrology and Rheumatology Departments of the Republican Clinical Hospital in 2004 to 2018 were retrospectively analyzed. Demographic data (gender, age at onset of the first signs of the disease, age at diagnosis of SLE, its duration, labor activity, and disability), clinical manifestations of the disease (damage to the  musculoskeletal system, skin and mucous membranes, kidneys, as well as serositis, neuropsychological disorders), and 5-, 10- and 15-year survival rates were analyzed. A hierarchical cluster analysis was used to group patients on the basis of the similarity in the measured characteristics.

Results and discussion. A total of 256 SLE patients (230 females and 26 males) were followed up. The median age at onset of the first symptoms of the disease for females and males was 29.0 [21.0; 38.0] and 25.5 [18.0; 37.0] years, respectively; the age at SLE diagnosis was 30.0 [23.0; 41.0] and 25.5 [18.0; 37.0] years. The main clinical manifestations of the disease were damages to the musculoskeletal system (n=199 (77%)), skin and mucous membranes (n=168 (66%)), and kidneys (n=155 (61%)), neurological disorders (n=39 (15%)) and serositis (n=83 (32%)). In the above period, 29 patients died in the study group; there are no data on 10 patients. The 5-, 10-, and 15-year survival rates of patients in our group were 93.7, 90.8, and 86.4%, respectively; those in patients with lupus nephritis (LN) were 90.4, 86.6, and 82.1%; those in hypertensive patients were 89.5, 84.6, and 79.3%. A cluster analysis identified four clusters. The most important criteria for grouping the patients into clusters were the presence of antiphospholipid syndrome (APS), LN, and hypertension. Cluster 1 included patients with LN and hypertension; Cluster 2 comprised those with APS, LN, and hypertension. Cluster 3 consisted of patients having hypertension only; Cluster 4 included those with LN only. In Cluster 2, the 10- and 15-year patient survival rates decreased to 77.9 and 70.1%, respectively.

Conclusion. In our study, 5-, 10-, and 15-year patient survival rates were 93.7, 90.8, and 86.4%, respectively. Gender and age at SLE diagnosis did not affect death rates. The risk of death was significantly higher in patients with LN and hypertension.  

160-164 564
Abstract

Recently, various visualization techniques have been used to study spondyloarthritis (SpA); indices are also being elaborated to assess the progression of radiographic changes in the spine and sacroiliac  joints. Most studies dedicated to the problem of coxitis in SpA have shown that its progression parallels with a spinal inflammatory process; however, no indices for assessing the time course of changes in the hip joints (HJs) have been developed.

Objective: to develop a method for assessing the radiographic progression of coxitis in early axial SpA (axSpA).

Subjects and methods. Examinations were made in 175 patients (mean age, 28±6 years) with axSpA who met the 2009 ASAS criteria and had an inflammatory back pain duration of no more than 5 years. The analysis included 62 patients who had been followed up for at least 2 years and had plain pelvic bone X-ray films at the inclusion in the cohort and at 2 years after starting the follow-up. The sum of stages of radiographic coxitis (ssrC) was used to assess HJ injury progression. During the study, a formula was developed to assess the progression rate of radiographic coxitis.

Results and discussion. The median difference in ssrC (ΔssrC) was 0.78 [0; 4] at baseline and at 2 years. During the study period, 63% of the patients showed no progression of ssrC; the latter increased by 1 score in 7 (11%) patients, by 2 scores in 11 (18%), by 3 scores in 1 (2%), and by 4 scores in 4 (6%). The ssrC averaged 0.54±0.79 at baseline and increased by 0.78 up to 1.32±1.34 (p=0.06) at 2 years. At baseline, the coxitis progression rate averaged 0.45 per year (it was conventionally accepted that the patients exhibited no signs of HJ injury at onset of the disease: ssrC was zero); that was 0.54 and 0.1 per year at 1 and 2 years of follow-up, respectively.

Conclusion. The proposed calculation procedure is easily feasible and applicable in real practice, does not lead to additional investigations, and is economically feasible. This procedure allows monitoring the rate of radiographic coxitis progression in patients with axSpA throughout the course of the disease.

165-170 552
Abstract

Objective: to comparatively analyze and estimate the prevalence of traditional cardiovascular risk factors (RFs) and the blood lipid spectrum in patients with rheumatoid arthritis (RA) and in those with psoriatic arthritis (PsA).

Subjects and methods. The investigation enrolled 48 patients (41 females and 7 males) (mean age, 51.3±4.3 years) with RA who fulfilled the 1987 American College of Rheumatology (ACR) criteria and 46 patients (25 females and 21 males) (mean age, 49.6±3.8 years) with PsA fulfilling the 2006 Classification Criteria for Psoriatic Arthritis (CASPAR) criteria who were treated in Dushanbe City Medical Center (CMC) Two in 2012 to 2019. The traditional and disease-related RFs of cardiovascular events (CVEs) were analyzed to identify the total cardiovascular risk using the SCORE and 2010 SCORE/EULAR scales; duplex scanning of the carotid arteries was performed to measure intima-media thickness and to identify atherosclerotic plaques; the blood lipid spectrum (total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDLC) and high-density lipoprotein cholesterol (HDLC)). The atherogenic index (TC-HDLC/HDLC) was calculated to determine the ratio of atherogenic to antiatherogenic lipoproteins.

Results and discussion. The most common RFs for CVEs in the examined patients with RA and in those with PsA were hypertension (64.5 and 58.6%, respectively) and dyslipidemia (58.2 and 69.2%). It was found that systemic inflammation and pharmacotherapy for RA and PsA were actively involved in the formation of an atherogenic lipid profile and that the incidence of CVEs increased in patients with RA and in those with PsA who had two or more traditional and the so-called disease-related RFs.

Conclusion. Our findings suggest that the development and progression of a wide range of CVEs in patients with RA and in those with PsA are based on the cumulative effect and complex interaction of chronic systemic autoimmune inflammation, traditional cardiovascular RFs, and long-term and uncontrolled use of nonsteroidal anti-inflammatory drugs and glucocorticoids, which assumes that CVEs have a multifactorial nature in RA and PsA.

PEDIATRIC RHEUMATOLOGY

171-177 721
Abstract

Objective: to analyze clinical features and immunological abnormalities in juvenile-onset systemic lupus erythematosus (SLE) with neurolupus and to compare findings with the data available in the literature.

Subjects and methods. The observational retrospective study included 218 patients (190 girls and 28 boys) with juvenileonset SLE who were treated at the Pediatric Department of the V.A. Nasonova Research Institute of Rheumatology in the period from 1992 to 2017. The investigators assessed demographic parameters, the data of clinical and laboratoryinstrumental examinations, and the results of psychological, neurological and, if indicated, psychiatric examinations. The clinical and immunological features of SLE onset were comparatively analyzed in the groups of patients with and without neurolepus, followed by a comparison of the findings with the data available in the literature.

Results and discussion. Forty-five (20.6%) patients with SLE and neuropsychiatric disorders were identified, of them there were 9 (20%) boys. In the neurolupus group, the mean age at onset was 13.0±2.8 years; the median disease duration at diagnosis verification was 5.0 [3.0; 11.0] months. 60% of patients were aged 10 to 15 years at diagnosis verification. Neurolupus was significantly more often detected in 46.7% of patients with acute SLE (p=0.003). Among the clinical manifestations of a nervous system lesion, serositis (p=0.003) and kidney disease (p=0.003) were diagnosed significantly more often; chronic skin changes (p=0.076) were recorded slightly more frequently, whereas arthritis (p=0.028) was detected significantly less frequently. Of the hematological disorders, leuko- and lymphopenia (p=0.087) and thrombocytopenia (p=0.077) were noted relatively more commonly. Of the immunological disorders, patients with nervous system lesion more frequently had anti-ribonucleoprotein antibodies (p=0.073) without any differences in other immunological parameters. In general, the neurolupus group showed a greater extent of multiple organ dysfunction than the other patients (the number of clinical manifestations averaged 5.6 and 3.7, respectively; p<0.0001).
In all the patients, the manifestation of neurolupus was preceded by school maladaptation and emotional disturbances. There was a preponderance of central nervous system lesion (89%) in the pattern of neuropsychiatric manifestations. Fifteen (33.3%) patients had more than one manifestation of neurolupus. Among the neuropsychiatric disorders, there were headaches (28.9%), cognitive impairment (28.9%), cerebrovascular disease (35.5%), distal sensory polyneuropathy (20%), epilepsy syndrome (15.5%), anxiety disorders (11.1%), psychoses (8.9%), myelopathy (6.7%), and chorea (4.4%). In the neurolupus group, the SLEDAI scores were significantly higher (22.0±9.5) than in the non-neurolupus group (12.9±6.5; p<0.0001).

Conclusion. When the patient has an acute onset, multiple organ dysfunction, psychological problems as emotional lability, proneness to conflict, and school maladaptation, he/she must undergo comprehensive examination to exclude neurolupus before the disease manifests. Identification of nervous system lesion requires urgent intensification of therapy to improve prognosis.

ORTHOPEDIC RHEUMATOLOGY AND REHABILITATION

178-182 645
Abstract

Chronic shoulder pain (CSP) is one of the most common reasons for seeking medical care. Identifying the specific cause of CSP is necessary to determine the treatment strategy.

Objective: to determine which pathology of the musculoskeletal system is the main cause of CSP.

Subjects and methods. A study group consisted of 151 patients (49.7% females; mean age, 49.8±18.8 years), who experienced shoulder joint pain that persisted when taking nonsteroidal anti-inflammatory drugs (NSAIDs) and after local administration of glucocorticoids. They underwent clinical and instrumental studies (radiography, magnetic resonance imaging, and ultrasound). The investigators assessed pain intensity using a visual analogue scale (VAS), and functional impairment with the American Shoulder and Elbow Surgeons (ASES) Assessment Scores and the Constant Score (CS).

Results and discussion. The mean CSP intensity at rest and during movement was 56.1±21.7 and 67.3±19.1 mm VAS. The degree of functional disorders was 55.5±17.6 ASES scores and 54.1±14.5 CS scores. Tendonitis that is an injury to the tendon of the supraspinatus muscle (74.8%) was most common. There was shoulder osteoarthritis (OA) in 31.7%, acromioclavicular (AC) OA in 19.2%, rotator cuff tendon injury concurrent with shoulder OA in 25.2%, that with AC OA in 16.6%, and that with shoulder OA and AC OA in 9.2%. The intensity of pain with only rotator cuff tendon injury and that  concurrent with shoulder OA and/or AC OA did not differ and that averaged 57.2±20.2 and 54.6±18.6 mm at rest, respectively, and 68.3±22.4 and 65.4±19.2 mm during movement (p>0.05 in both cases).

Conclusion. The main cause of CSP is tendonitis of the rotator cuff, primarily of the supraspinatus muscle. Moreover, more than half of patients have rotator cuff tendon injury concurrent with biceps tendon injury, shoulder OA and/or AC OA. 

ОБЗОРЫ

183-190 5470
Abstract
Immune-mediated inflammatory diseases (IMIDs) belong to the most severe chronic human diseases. The leading mechanisms of the development of IMIDs are, in the broad sense of the word, autoimmune and/or autoinflammatory immunopathological processes, the former of which is characterized by the preponderance of activation of acquired immunity, and the latter is by that of innate immunity. A broad spectrum of anti-inflammatory drugs is used to treat IMIDs. Regardless of their structure and molecular targets, the dominant universal effect of the drugs is in suppressing inflammation. A special place is occupied by colchicine that is an alkaloid extracted from meadow saffron (Colchicum autumnale), which has been used to treat joint inflammation for more than 2 thousand years, and has unique, not fully deciphered mechanisms that determine its anti-inflammatory and analgesic effects. Owing to the deciphering of the molecular mechanisms of action of colchicine in suppressing the autoinflammatory mechanisms in the immunological pathogenesis of IMIDs, the interest in colchicine has substantially increased and contributed to the expansion of indications for its use in medicine.

191-197 980
Abstract
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. A special place in the spectrum of joint injuries in patients with SLE is occupied by osteonecrosis (ON) that is considered as a severe complication of the disease. Recent advances in the diagnosis and treatment of SLE and a considerable increase in patient survival rates necessitate maintenance of the adequate quality of life for patients. In hip ON, total arthroplasty is the main method for surgical correction, which makes it possible to control pain and to improve quality of life and functional ability in patients. Despite the rather long history of applying this method, the problem of assessing the long-term results of total hip arthroplasty and the incidence of postoperative complications in patients with SLE has not been fully investigated.

YOUNG SCIENTISTS FORUM

198-206 1362
Abstract
The literature review considers the fundamental elements of a relationship between cancers and rheumatic diseases, including a variety of paraneoplastic syndromes, a profile of rheumatic diseases associated with the development of oncopathology, and autoimmune rheumatic syndromes detected in patients who receive anticancer therapy. Emphasis is placed on the need for interdisciplinary interaction to deepen understanding of the pathophysiological mechanisms of both groups of diseases and to improve medical care for patients.

POSTGRADUATE PROGRAM OF CONTINUING MEDICAL EDUCATION

207-213 782
Abstract
Hepatitis B virus (HBV) is often found and associated with immune-mediated inflammatory rheumatic diseases (IMIRDs), necessitating the modification of both antiviral and antirheumatic therapies. The review provides basic information about the structure of HBV, the course of chronic HBV infection, and the prevention of HBV reactivation in patients with IMIRDs who receive immunosuppressive therapy.

PROGRESS IN RHEUMATOLOGY IN THE XXI CENTURY

214-224 853
Abstract
The design of targeted oral anti-inflammatory drugs, such as Janus kinase (JAK) inhibitors, the first representative of which is tofacitinib (TOFA), is considered a major achievement in biology and medicine early in the 21st century. Part I of the review considers the materials of studies evaluating the efficacy and safety of TOFA in rheumatoid arthritis (RA). The expansion of ideas about the mechanisms of development  and chronicity of inflammation and the antiinflammatory and immunomodulatory effects of TOFA using a  RA model has created theoretical and clinical prerequisites for studying the efficacy of TOFA in other  immune-mediated inflammatory rheumatic diseases (IMIRDs) and chronic inflammatory non-rheumatic diseases. Part II of the review summarizes new data that allow one to formulate main areas of further clinical and fundamental studies, the objective of which is to expand indications for and to personalize therapy with JAK inhibitors in patients with IMIRDs.

CLINICAL OBSERVATIONS

225-231 2969
Abstract
The paper describes a clinical case of a male patient with verified systemic lupus erythematosus (SLE) and manifestations of lupus nephritis with impaired renal nitrogen excretory and filtering functions, central nervous system lesion (focal epilepsy), hematological (hemolytic anemia) and immunological (anti-double-stranded DNA antibodies, hypocomplementemia, positive antinuclear factor) disorders, and antiphospholipid syndrome (APS). The disease originated from APS: thrombosis in the radial and ulnar arteries. Subsequently, organ damages were considered as a consequence of thrombotic microangiopathy, which can occur with both APS and SLE.

232-237 626
Abstract
At present, there is more and more evidence in rheumatology on the factors influencing the efficacy of biological agents (BAs), and there is no generally accepted algorithm for managing patients resistant to standard therapy. The paper describes three patients with ankylosing spondylitis (AS) who were followed up at the V.A. Nasonova Research Institute of Rheumatology in 2011–2019. All the patients showed a severe course of AS of high clinical and laboratory activities, extra-articular manifestations, and inefficacy of three or more BAs. All the patients share the following symptoms: male gender, early onset of disease, high clinical and laboratory activities, and extra-articular manifestations, such as uveitis and psoriasis.

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