The author discusses the need for scientific communication, knowledge about impact indicators and other criteria for assessing scientific publications, as well as current approaches to choosing journals to publish the results of researches. The high level of Russian rheumatology and the quality of articles published in the journal «Nauchno-Prakticheskaya Revmatologiya» (Rheumatology Science and Practice) are mentioned.

Systemic sclerosis (SS) is a progressive connective tissue disease, the prognosis of which largely depends on the time of adequate therapy initiation. Low sensitivity of the 1980 American College of Rheumatology (ACR) SS classification criteria for identifying patients with early stage of the disease, and with its limited form in particular, has necessitated revision of existing SS diagnostic standards and elaboration of more sensitive criteria that allow to establish the diagnosis when the first sign of the disease appear.

Objective: to compare the sensitivity of the novel SS criteria of ACR and European League against Rheumatism (ACR/EULAR) 2013 and the 1980 ACR criteria in different stages of the disease.

Subjects and methods. The investigation enrolled 302 patients who had been diagnosed by experts as having SS and followed up at the V.A. Nasonova Research Institute of Rheumatology in 2007–2013. The patients’ mean age was 49±13 years (18 to 80 years); male to female ratio – 1:9 (31 and 271), that of patients with diffuse and limited SS – 1:2 (105 and 197); mean duration of the disease from the first non-Raynaud’s syndrome was 8.2±7.0 years (6 months to 36 years). Physical examination, nailfold capillaroscopy, chest radiography or computed tomography, echocardiography for the determination of pulmonary artery systolic pressure and SS-specific antibodies evaluation were performed.

Results. 273 (90%) patients fulfilled the novel ACR/EULAR 2013 SS criteria. 76 (25%) patients had skin thickening above the metacarpophalangeal (MPC) joints in both hands; 263 (87%) – finger skin thickening [70 (23%) – finger swelling, 192 (64%) – thickening of all fingers distal to the MPC joints], 141 (47%) – digital ischemia [79 (26%) – digital pitting scars, 20 (7%) – digital ulcers, 42 (14%) – digital pitting scars and ulcers], 134 (44%) – telangiectasias, 276 (91%) – capillaroscopic changes, 225 (78%) – pulmonary hypertension (PH) or interstitial lung disease (ILD) [15 (5%) – PH 185 (61%) – ILD, 35 (12%) – ILD and PH], 301 (99%) – Raynaud’s phenomenon, and 185 (61%) – SS autoantibodies [138 (46%) – anti-Scl-70 antibodies (a-Scl-70), 42 (14%) – anti-centromere antibodies (ACA), 5 (1.7%) – ACA and a-Scl-70]. 216 (72%) patients fulfilled 1980 ACR SS criteria, and all of them met the novel criteria. With the latter, SS could be additionally diagnosed in 57 more (18%) patients.

Conclusion. The 2013 ACR/EULAR SS classification criteria have much higher sensitivity than the 1980 ACR criteria. The sensitivity of the novel criteria remained at the level of 90% in all, including the earliest, stages of the disease while the ACR criteria allowed to confirm diagnosis of SS in only half of patients with a disease duration of less than 1 year.

Objective: to estimate the contribution of HLA-B5/51 genotype to the clinical manifestations and risk of Behcet’s disease (BD) in two ethnic groups.

Subjects and methods. 146 BD patients fulfilling the International Criteria for BD (ICBD) were divided into two ethnic groups: 1) 86 patients from Dagestan (representatives of 8 ethnic nationalities in this region) with mean age 30.7±9.6 years; disease duration – 8.8±10.1 years; 2) 60 ethnic Russian patients, nonresidents of Dagestan with mean age 32.9±11.1 years; disease duration – 11.2±10.1 years. All patients were examined at the V.A. Nasonova Research Institute of Rheumatology in 1990 to 2014. HLA class I antigens were typed by a microlymphocytotoxic technique using a Gisans anti-leukocyte sera kit (Saint Petersburg).

Results. HLA-B5/51 was detected in 87 (59.6%) patients, much more often in men than in women (70 and 38%, respectively; p<0.01). Genital ulcers and erythema nodosum were significantly more common in HLA-B5/51-positive Dagestani (87.3 and 57%) than in HLA-B5/51-negative ones (56.5 and 26%; p=0.0019 and р=0.01; respectively). There were no significant differences in these signs in the Russian group of patients with BD depending on the presence of this allele. In HLA-B5/51-positive male Dagestani patients with BD, the risk of erythema nodosum was twice as high as that in HLA-B5/51-negative patients (p=0.054). In HLA-B5/51 female Dagestani carriers, the risk of genital ulcers and generalized uveitis proved to be 3.5 (p=0.057) and 2.7 times higher than that in HLA-B5/51 noncarriers. Frequency of HLA-B5/51 was 73.2% among the Dagestanis and 40% among the Russians. Furthermore, this investigation revealed HLA-B5/51 carriage mainly in the male BD patients. Therefore, in addition to ethnicity, gender should be borne in mind when analyzing the clinical associations with HLA-B5/51.

Objective: to evaluate the safety of treatment with methotrexate (MT) solution for subcutaneous injections in patients with rheumatoid arthritis (RA).

Subjects and methods. 237 RA patients enrolled in the study within the REMARCA protocol were given MT solution for subcutaneous injections (Metoject) to assess the standard parameters of therapy safety.

Results. Overall, adverse events (AE) were noted in 49 (21%) patients. In 30 (30%) of them RA duration was less than 6 months (Group 1) and in 19 (14%) – more than 6 months (Group 2), in most cases average MT dose was 20.9±3.45 mg/week. Elevation of alanine aminotransferase and aspartate aminotransferase levels, nausea, postinjection reactions, alopecia, rash, infections, and leukopenia, were common (> 1%, but <10%); diarrhea, metallic taste in the mouth, soft tissue abscess/infiltration developing far from the injection site, were uncommon (the WHO term corresponding to 0.1–1%). AE required MT discontinuation in 4.2% of the patients.

Conclusion. The results of the study allow discussing subcutaneous MT administration before treatment with biologicals, which makes it possible not only to reduce financial expenditures, but also to improve patient safety

Objective: to study the rate of gout and calcium pyrophosphate deposition disease (CPDD) and to provide their clinical characteristics in patients with acute arthritis.

Subjects and methods. The investigation enrolled 150 patients (97 men and 53 women) with acute mono- or oligoarthritis of no more than 2 weeks’ duration who had visited the Outpatient Department of V.A. Nasonova Research Institute of Rheumatology. Their mean age was 60.2±12.0 years (range, 28–76 years). All the patients underwent inflamed joint puncture and synovial fluid (SF) crystal identification by polarized microscopy using an Olympus CX31-P compensator.The diagnosis of CPDD was established in compliance with the criteria elaborated by D. McCarty. Gout was diagnosed only when sodium monourate (SMU) crystals were found in SF.

Results and discussion. The investigation revealed gout in 51 (34%) patients, CPDD in 45 (30%), coincidence of gout and CPDD in 15 (14%), and 39 (26%) patients had other diseases: 15 (10%) – osteoarthritis, 6 (4%) – rheumatoid arthritis, 5 (3%) – septic arthritis, 5 (3%) – psoriatic arthritis, 2 (1%) – ankylosing spondyloarthritis, 4 (3%) – injury, and 5 (3%) – undifferentiated spondyloarthritis. There were 40 men and 11 women among the patients with gout and 13 men and 32 women among those with CPDD. The patients with gout were younger than those with CPDD (35.5±8.9 and 58.4±12.8 years, respectively; p < 0.05). In the patients with CPDD, knee, ankle, and first metatarsophalangeal joint arthritis was present in 34 (76.3%), 17 (30.3%), and 4 (9%) cases, respectively. Arthritis developed within a few hours in 90% of the patients with gout and in 33.3% of those with CPDD (p < 0.001). Monoarthritis was significantly more common in gout whereas oligoarthritis – in CPDD (p < 0.05). Visual analog scale pain intensity averaged 78.4±12.5 mm and 54.32±22.02 mm (p < 0.05), duration of arthritis – 10.3±3.8 days and 3.4±2.1 days (p < 0.05) in gout and CPDD respectively.

Conclusion. CPDD is the most common (60%) cause of acute arthritis in women and the second most frequent (13%) cause in men (following gout). Acute arthritis develops more slowly and persists for a longer period of time in patients with CPDD than in those with gout.

Objective: to analyze changes of serum calprotectin (CP) concentration, its relationship to the clinical and laboratory parameters of rheumatoid arthritis (RA) activity, and the significance of baseline CP level for predicting therapeutic response in RA patients treated with etanercept (ETC).

Subjects and methods. A total of 84 patients with moderate and high RA activity (mean DAS28 6.35±0.92) who had been ineffectively treated with disease-modifying antirheumatic drugs were examined. The patients received ETC 50 mg/week subcutaneously for 34 weeks. To assess RA activity, tender and swollen joint count, pain, patient’s and physician’s assessment of global disease activity on 100-mm visual analogue scale and DAS28 were used. Functional status was evaluated by HAQ and RAPID3. Treatment efficacy was assessed according to the European League against Rheumatism (EULAR) criteria and the American College of Rheumatology (ACR) criteria. Serum concentration of CP was tested before, 12 and 25 weeks after start of therapy.

Results and discussion. There was a statistically significant (p < 0.0001) decrease in CP concentrations after 12 weeks of ETC therapy. Later (after 25 weeks) CP level remained essentially unchanged. CP concentration correlated with erythrocyte sedimentation rate, C-reactive protein level, swollen joint count, and DAS28. Baseline CP level was not a predictor for achieving the therapeutic response according to the EULAR and ACR criteria. In a group of patients unresponsive to treatment according to the EULAR criteria, CP levelrose at 25 weeks whereas it fell during clinical improvement. In the patients achieving ACR 50 and 70% response, changes of CP level were significantly better than those in the other patients.

Conclusion. ETC therapy caused a considerable reduction of CP level, clinical and laboratory parameters of RA activity. The baseline concentration of CP was not a predictor for achieving the response to ETC treatment.

Objective: to assess the association of cytokine profile measures with disease activity, autoantibody levels, and joint destructive changes in patients with early rheumatoid arthritis (RA).

Subjects and methods. Forty-five patients, including 35 women, with early RA were examined. Their median age was 53.5 [46; 59.5] years; the duration of the disease – 7.0 [4.0; 11.5] months; DAS28 – 5.8 [4.9; 6.4]; 91 and 96% of the patents were positive for rheumatoid factor (RF) and anticyclic citrullinated peptide antibodies, respectively. Serum cytokine concentrations were estimated using the xMAP multiplex technology. The modified Sharp method was employed to quantify radiographic changes.

Results and discussion. A group of 30 patients with high disease activity (DAS28 >5.1) had higher levels of interleukin (IL)-6 (62.3 [36.1; 127.5] pg/ml) and IP-10 (6367.8 [3682.7; 10691.3] pg/ml than 15 patients with moderate/low disease activity (DAS28 ≤5.1) (35.8 [13.4; 64.2] and 3222.6 [1881.0; 5671.9] pg/ml, respectively, p < 0.05). The patients highly positive for IgM RF had higher levels (pg/ml) of proinflammatory cytokines, such as IL-1β, IL-2, IL-6, IL-12, IL-15, interferon-γ, and tumor necrosis factor-α; the chemokine monocyte chemotactic protein-1 and the growth factors IL-7 and vascular endothelial growth factor (4.8 [2.8; 19.3], 23.0 [7.1; 55.8], 64.2 [41.6; 170.5], 52.2 [30.9; 126.9], 2.4 [0.2; 
11.2], 210.8 [119.9; 584.2], 90.7 [42.7; 307/9], 57.5 [26.1; 93.8], 54.9 [37.1; 123.7], and 143.3 [70.6; 249.6] pg/ml) than those who were negative/lowly positive for IgM RF (2.3 [1.9; 3.1], 4.9 [2.9; 16.8], 24.9 [20.4; 45.4], 25.6 [19.9; 57.1], 0.2 [0.01; 1.65], 94.4 [86.3; 138.9], 37.3 [23.6; 47.7], 20.9 [12.3; 33.9], 32.6 [28.1; 37.8], 74.2 [53.5; 147.6], respectively (p < 0.05)).

Conclusion. There are significant differences in cytokine profile measures in patients with early RA in relation to disease activity and serum autoantibody levels.

Objective: to evaluate the impact of orlistat therapy on the clinical manifestations of knee osteoarthritis (OA) in obese patients.

Subjects and methods. The investigation enrolled 50 women aged 45–65 years with Kellgren–Lawrence Stages II–III knee OA and obesity [body mass index (BMI) > 30 kg/m2] who were randomized into 2 groups: 1) 25 patients who took Orlistat in a dose of 120 mg (one capsule) thrice daily for 6 months in conjunction with a low-calorie diet and exercise; 2) 25 patients who received only non-drug therapy for obesity (a low-calorie diet and exercise). The investigators assessed anthropometric measures, WOMAC index, and health status using a visual analogue scale.

Results and discussion. After 6 months, group 1 had more marked weight loss than group 2: 10.0% (mean 10.5 kg) and 0.8% (mean 1 kg) respectively. Orlistat also provided more pronounced reduction of WOMAC pain scores, functional insufficiency and WOMAC index than non-pharmacological therapy (by 52.2% and 28.8%, р ≤ 0.05, by 51 and 18%, р ≤ 0.05 and by 51 and 19%, p = 0.006 respectively). Moreover, group 1 showed significant improvement of quality of life as compared to group 2 (p < 0.001). The tolerability of Orlistat was good; only two patients reported diarrhea due to dietary errors (fat intake), which required no drug discontinuation.

Conclusion. The investigation has demonstrated that body weight loss provided by appropriate medications leads to the regress of clinical manifestations of knee OA in obese patients: pain relief and functional improvement. So drugs contributing to weight los, should be incorporated into treatment regimens for patients with OA and obesity.

When treating rheumatoid arthritis (RA), it is important not only to suppress inflammation, but also to prevent local and generalized bone loss, particularly in patients receiving glucocorticoids (GC). Denosumab is a fully human monoclonal antibody that binds receptor activator of nuclear factor kappa B ligand (RANKL), prevents its interaction with receptor on osteoclasts, reduces their activity, and inhibits bone resorption.

Objective: to evaluate the effect of 12-month therapy with denosumab on bone mineral density (BMD) of the axial
and peripheral skeleton and destructive changes in the hand and foot joints of RA patients receiving GC.
Subjects and methods. Fifty-two postmenopausal women with RA concurrent with osteoporosis received subcutaneous denosumab 60 mg twice: at baseline and 6 months later. BMD was measured before drug administration and after 12 months of a follow-up, by applying dual-energy X-ray absorptiometry of three sections: the lumbar spine (LI–IV), femoral neck (FN), and distal forearm (DF). Radiographic changes in the hand and foot joints were assessed using the Sharp method modified by van der Heijde (SVH) at baseline and 12 months later.

Results and discussion. The patients’ mean age was 58.4±6.4 years; the mean RA duration – 19.0±10.9 years. Antiinflammatory
therapy was performed in all the patients, including 30 (57.7%) who received GC. The mean BMD during follow-up increased from 0.814±0.101 to 0.848±0.103 g/cm2 in LI–IV (p<0.001), from 0.629±0.089 to 0.641±0.090 g/cm2 in FN (p=0.02), and from 0.497±0.094 to 0.502±0.091 g/cm2 in DF (р=0.34). The patients receiving and not  receiving GC showed a significant increase in LI–IV BMD and a tendency for its rise in FN and DF. There was a significant increase of X-ray changes in the hand and foot joints. Seven of the 52 patients were found to have a larger number of erosions: 33.0 [4.0; 78.0] at baseline and 39.0 [5.0; 90.0] after 12 months (p=0.017); 5 patients had a larger number of narrowed joint spaces: 119.0 [18.0; 140.0] and 124.0 [20.0; 146.0] (р=0.043); the total SVH score increased in 8 patients: 175.5 [54.0; 221.5] and 182.0 [57.0; 235.0] (р=0.011), respectively. Moreover, dividing the patients into groups according to the use of GC revealed significant increase of the number of erosions and total SVH scores only in the patients receiving GC.

Conclusion. Therapy with subcutaneous denosumab 60 mg twice a year at a 6-month interval could significantly increase LI–IV BMD regardless of GC intake. Progression of radiographic joint changes was noted mainly in patients receiving GC

The paper presents data on the role of vitamin D and calcium in the function of many human organs and tissues. Lifestyle, dietary preferences, and insufficient physical activity contribute to the high prevalence of vitamin D and calcium deficiencies in the adult population of Russia, causing different diseases and abnormalities. The authors have worked out recommendations for the preventive use of vitamin D and calcium in healthy population, give consumption rates for these substances, and describe the clinical and laboratory signs of vitamin D deficiency and indications for screening. They also propose treatment regimens for vitamin D deficiency and depict the signs of intoxication in
overdose. Particular emphasis is laid on the place of vitamin D and calcium in the therapy of osteoporosis.

Ankylosing spondylitis (AS) is a chronic systemic disease of the axial skeleton. Recently, there has been increased interest among practitioners and researchers in AS. Because of difficulties in conducting epidemiological surveys studying statistical data on its prevalence and patient mortality is of great importance. It permit introduction of necessary corrections into organization of medical care to patients on the basis of analysis of the situation in the region.

Objective: to study the trend and validity of data on AS prevalence and patient mortality in the adult population of the Tula Region versus the Russian Federation.

Subjects and methods. The investigators used the 2002–2010 statistical guidelines “Prevalence of diseases in adult population
of Russia” by the Ministry of Health of Russia; the 2006–2010 federal statistical inquiry forms No. 14 in the Tula Region and the Russian Federation; the European hospital database; the 2000–2011 mortality databases in the Tula Region, which had been obtained by the automated mortality registration systems, which contained 373,997 records and included all margins of “Medical Death Certificates”.

Results and discussion. In the Russian Federation, overall prevalence of AS per 100,000 adult population increased from 27.6 in 2002 to 34.4 in 2010 (the increment was 24.6%) while in the Tula Region its trend was unstable in this period. Incidence of AS here decreased by 31.8% from 2002 to 2010; in Russia its increment was 51.6%. From 2000 to 2011 in the Tula Region AS was registered as one of the causes of death in 29 cases.

Conclusion. To plan measures aimed at improving the quality of medical care to AS patients, it is necessary to expand a comprehensive study of AS prevalence as well as outpatient and inpatient mortality from AS

At present, the problem of reactive arthritis (ReA) remains relevant in rheumatology. This is due to rather high prevalence of the disease primarily in Russia, which cannot but alarm. Analysis of epidemiological findings suggests a number of possible explanations for variability of ReA incidence rates in some regions of the Russian Federation and other countries. The lecture details the clinical presentations of the disease and analyzes the significance of different laboratory procedures aimed at detecting the pathogen of ReA. It presents Russian diagnostic criteria for ReA. It also sets forth basic approaches to ReA therapy with emphasis on the use of antimicrobial drugs. The efficiency and safety of drug immunomodulation (interferon inducers, polyoxidonium, immunofan, etc.) in treating urogenital Chlamydia infection in ReA patients are not confirmed by the data of randomized controlled trials. In this connection, it is impossible to give any recommendations for their use in urogenic ReA.

As new effective biological agents (BAs) are being widely introduced, in the past decade there have been serious changes in the rheumatoid arthritis (RA) strategy: its basis was the treat-to-target concept. It is emphasized that the basic strategy component is active early aggressive therapy with methotrexate (MT) and, if MT monotherapy is inadequately ineffective, combined therapy with MT and standard disease-modifying antirheumatic drugs or MT and BAs.
Although oral MT is more frequently prescribed in randomized placebo-controlled trials (RPCTs) and in clinical practice, there is now a tendency towards the wider use of its subcutaneous formulation. Novel evidence from fundamental studies dealing with the deciphering of the mechanism of MT action and the materials of numerous RPCTs, observational studies, and national registries substantiate the unique place of MT in the treatment of RA, its complications, and comorbidities. The purpose of the review is to analyze new data on the mechanism of action of MT and its 
clinical efficacy and safety in rheumatology.

Systemic sclerosis (SS), is an autoimmune connective tissue disease, the main clinical signs of which are due to disseminated microcirculatory disorders and fibrosis of the skin and viscera. Morphological examinations showed that 80% of patients with SS had renal changes, including those unassociated with rheumatic diseases. Whereas the prevalence of scleroderma renal crisis is now estimated to be 2–5%, there is considerably often an asymptomatic reduction in renal function (silent uremia), which is caused by multimorbidity and comorbidity. Its incidence in patients with SS may be as high as 55%. The presence of autoimmune connective tissue disease may be itself regarded as a risk factor of renal involvement. Fifteen-year survival is 72% in SS patients with no renal involvement and not more than 13% in those having renal involvement. In patients with SS, proteinuria is one of the most important independent risk factors for fatal outcomes (relative risk, 3.34), leaving far behind canonical risk factors, such as pulmonary hypertension, restrictive lung disease (a forced expiratory volume in one second to forced vital capacity ratio of <80%), respiratory failure (NYHA Class III and IV), as well as decreased lung diffuse capacity and high skin scores. The authors first propose a concept of the existence and pathogenesis of chronic scleroderma nephropathy, the basis for which is the vascular endothelial dysfunction phenomenon developing in different structural components of the nephron and kidney as a whole.

The paper describes a patient with refractory systemic juvenile arthritis treated with tocilizumab (TCZ). Specific features of therapeutic response in real clinical practice, aspects of individual TCZ safety in the development of macrophage activation syndrome and concurrent therapy are discussed.

Hip joint injury, coxitis, is a characteristic manifestation of ankylosing spondylitis. Coxitis therapy has not been elaborated so far. There are few publications on the efficacy of tumor necrosis factor-α inhibitors. Alternative pharmacotherapies, including use of methotrexate, have not fully been studied. The study describes clinical cases of coxitis treated in patients with early spondyloarthritis.

The paper describes a long-term observation and discusses the possible mechanism of leflunomide-induced clinical and morphological regression of AA-amyloidosis diagnosed at a nephrotic stage in the presence of adult-onset Still's disease.