The undoubted and legitimate interest of investigators in comorbidities in rheumatic diseases has not faded in the past decade; however, the concept of multimorbidity has not yet been integrated into either clinical practice or rheumatology researches. The terms comorbidity and multimorbidity are frequently and not always consciously used as interchangeable, which leads to some confusion in their terminology and accordingly in the development of further research strategies. The concepts of concurrent pathology and multimorbidity are not mutually exclusive or contradictory to each other, but they should be considered from another point of view than comorbidity. The problem of multimorbidity disease is a rule rather than an exception to clinicians who are engaged in the treatment of mainly typical patients with rheumatic diseases. Recent researches could outline few key areas to further study the conception of multimorbidity in rheumatology practice, which would be able to turn international rheumatology research community from rheumatic disease to the patient as a whole.

The paper considers the joint management of rheumatoid arthritis patients needing endoprosthetic replacement of the large joints of the lower extremities by rheumatologists and orthopedic traumatologists.
Due to the fact that there are no conventional standards or guidelines for the perioperative management of patients with rheumatic diseases, adopted by international rheumatology associations, the authors generalize their experience in managing the patients in terms of international approaches and guidelines from different countries. The medical assessment and reduction of cardiovascular risks, the prevention of infectious complications, hemorrhages, and lower extremity deep vein thrombosis, and the specific features of management of patients with osteoporosis are under consideration. The authors' experience in managing the patients receiving antirheumatic therapy with nonsteroidal antiinflammatory and disease-modifying antirheumatic drugs, such as methotrexate, leflunomide, sulfasalazine, and hydroxychloroquine, is detailed. Recommendations for managing patients taking glucocorticoids and biologic agents (tumor necrosis factor-α inhibitors, anti-B-cell therapy, and interleukin-6 receptor inhibitors) in the preoperative and
postoperative periods are given.

The aim of a treat-to-target (T2T) strategy is to achieve a remission or minimal disease activity (MDA).

Objective: to investigate the efficiency of the T2T strategy for early psoriatic arthritis (ePsA).

Subjects and methods. Twenty-three patients (8 men and 15 women) with ePsA, who met the CASPAR criteria (mean age was 39.1±10.6 years; the median duration of ePsA was 7 [4; 24] months and that of psoriasis was 36 [12; 84] months), were examined. At the patient inclusion and then every 3 months, the investigators assessed the activity of ePsA by DAS and DAS28 and that of psoriasis by BSA (%) and PASI and determined erythrocyte sedimentation rate (ESR) (mm/h), C-reactive protein (CRP) level (mg/l), HAQ. All the patients received monotherapy (MoT) with subcutaneous methotrexate (MTX) (methoject) in a dose of 10 mg/week that was increased by 5 mg every 2 weeks until 20–25 mg/week was reached. The number of patients who had achieved remission (DAS <1.6 or DAS28 ≤ 2.4), low disease activity (LDA) (1.6 ≤ DAS <2.4 or 2.4 < DAS28 ≤ 3.6), MDA, and 20%, 50%, and 70% improvements according to the American College of Rheumatology (ACR) criteria. When LDA/MDA or remission was absent at 3 months of treatment, combined therapy (CoT) with MTX and adalimumab 40 mg once two weeks was used.

Results. The baseline median DAS was 3.97 [3.07; 4.67]; DAS28 – 4.33 [3.68; 4.73], PASI, 6 [3.1; 9.7]; BSA, 1 [0.5; 3.65]; CRP, 15 [8.6; 25.1] mg/l; ESR, 15 [8.6; 25.1] mm/h; and HAQ, 0.75 [0.63; 1.25]. After 3 months of MoT, remission defined by DAS and DAS28 was in 13/22.7% of the patients; LDA in 21.7/27.3%, and MDA in 26.1%, respectively. ACR 20, 50, and 70 responses were obtained in 65.2, 26.15, and 8.7% of the patients, respectively. There were significant decreases in the level of CRP (to 5.7 [2.3; 10.7] mg/l), HAQ (0.38 [0; 0.87]), BSA (1 [0.3; 2]), and PASI (7.1 [0; 32.5]). ESR remained substantially unchanged (18 [10; 26] ml/h). Four patients with persistent high disease activity were given CoT; 19 patients continued MTX MoT. After 6 months, DAS/DAS28 remission was in 34.8/39.1% of the patients; DAS/DAS28 LDA in 26.1/39.1%; and MDA in 47.8%, respectively. ACR 20, 50, and 70%
improvements were seen in 73.9, 60.9, and 47.8% of the patients, respectively. There were significant reductions in the level of CRP (4.9 [0.9; 8.3]), HAQ (0.13 [0; 0.63]), and BSA (0.35 [0; 1.6]). After MTX MoT, DAS/DAS28 remission was observed in 36.8/36.8% of the 19 patients; LDA in 15.8/36.8%; and MDA in 47.4%. ACR 20, 50, and 70 responses were seen in 68.4, 52.6, and 42.1% of the patients receiving MTX MoT and in 100, 100, 75% of the patients (n = 4) having CoT, respectively; MDA was noted in 50% of the cases.

Conclusion. The use of the T2T strategy during a 6-month period could provide ACR 70 response and MDA in half of the patients and remission in one third of the patients with ePsA.

Objective: to estimate the level of cardiovascular risk in patients with early rheumatoid arthritis (RA) before therapy with disease-modifying antirheumatic drugs (DMARDs).

Subjects and methods: Seventy-three patients with early RA who had not previously taken DMARDs or glucocorticoids were examined. Disease activity was assessed by the DAS28, SDAI, and CDAI. All the patients were examined by a cardiologist. The investigators assessed traditional risk factors (RF), by determining the overall coronary risk according to
the modified SCORE scale, the degree of a risk for cardiovascular events (CVE), carried out 24-hour ECG and blood pressure monitoring, echocardiography (EchoCG), and carotid duplex scanning, identified coronary artery calcification by multislice spiral computed tomography, and, if indicated, performed stress EchoCG and coronary angiography.

Results. The diagnosis of coronary heart disease was established in 13 patients. NYHA functional class I or II chronic heart failure (HF) was diagnosed in 8 patients, systolic HF in 2, HF with preserved left ventricular ejection fraction in 6 cases. There was left ventricular hypertrophy in 22 (30.1%) patients, carotid atherosclerotic plaques in 26 (35.6%), coronary artery calcification in 30 (41.1%), hypertension in 38 (52.1%), abdominal obesity in 34 (46.6%), dyslipidemia in 40 (54.8%), hypercholesterolemia in 37 (50.7%), hypoalphalipoproteinemia in 21 (28.8%), hypertriglyceridemia in 12 (16.4%), low physical activity in 30 (41.1%), and smoking in 13 (17.8%). Thirty-three of 53 women were
menopausal. Fasting hyperglycemia was found in 11 (15.1%) patients; type 2 diabetes mellitus in 4 (5.5%). Thirty-one (42.5%) patients had at least three RFs. In accordance with the current classification of the degree of cardiovascular risk, very high, high, moderate, and low risks for CVE were observed in 58, 8, 8, and 26% of the RA patients, respectively.

Conclusion. Most rheumatoid factor- and anticyclic citrullinated peptide-positive patients with early RA and high disease activity have high and very high cardiovascular risks.

Estimation of serum procalcitonin (PCT) levels is of great interest in rheumatology in both the diagnosis of coinfections
and the differential diagnosis between rheumatic disease activity and the current infectious process.

Objective: to estimate the value of PCT as a specific marker for generalized and local infection in rheumatic patients.

Subjects and methods. A retrospective study investigated the case histories of 100 inpatients examined and treated at the V.A. Nasonova Research Institute of Rheumatology. Serum PCT concentrations were determined by a quantitative electrochemiluminescence assay using a Cobas E 411 analyzer (Roche, Switzerland).

Results. Infectious diseases were diagnosed in 41 of the 100 patients. The infectious process was generalized and local in 11 and 30 cases, respectively. In the patients with generalized infection, the level of PCT was more than 2.0 ng/ml in 81.8% of the cases. In the local infection and non-infection groups, it was below 0.5 mg/ml in 70 and 84.7% of
cases, respectively. In the generalized infection group, the content of PCT was significantly higher (3.6 [2.3; 10.5]) than in the local infection (0.24 [0.15; 0.7]; р = 0.004) and non-infection (0.15 [0.09; 0.26]; р = 0.0001) groups. It did not depend on rheumatic disease activity. C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR)
correlated with PCT concentrations in different patient groups. ROC analysis showed the optimal sensitivity (82%) and specificity (98%) of PCT as a marker of systemic infection only in the rheumatic patients with its concentration of ≥2.3 ng/ml.

Conclusion. The determination of PCT is certain to contribute to the diagnosis of generalized infections and the differential diagnosis of systemic rheumatic diseases and infectious ones.

Osteoporosis (OP) in rheumatoid arthritis (RA) is 2–3 times more common than in the population; however, the data on the risk factors (RFs) of OP in this disease are ambiguous.

Objective: to study RFs for OP in RA within the framework of the multicenter program “Osteoporosis in rheumatoid arthritis: Diagnosis, risk factors, fractures, treatment”.

Subjects and methods. The trial enrolled 261 women (mean age 56.7±11.4 years) with RA; of them 151 (59%) patients were found to have OP (Group 1) and 107 (41%) were not (Group 2). All the patients underwent unified clinical, laboratory, and instrumental examination.

Results. Comparison of the patients with and without OP showed that the women with OP were older (59.5±10.8 and 52.9±11.2 years, respectively; p < 0.01) had longer RA duration (14.5±9.2 and 11±8.0 years; p < 0.01), higher Health Assessment Questionnaire (HAQ) functional disability index scores (1.7±0.8 and 1.4±0.9; p < 0.01), higher C-reactive protein (CRP) levels (13.5 [7; 31] and 11 [2,7; 26] mg/l; p < 0.01); a larger number of erosions (49 [11; 90] and 8 [1;36]; p < 0.01), and a more marked joint space narrowing (112 [90; 131] and 77 [51; 102]; p < 0.01). The women with OP received longer (72 [26.5; 120] and 48 [11; 79.5] months; p < 0.01) and more frequently glucocorticoids (GC) orally (65.6 and 38.3%; p < 0.01) and as pulse therapy (41.2 and 20.4%; p < 0.01), had a larger cumulative dose (14.4 [5.4; 24.2] and 7.2 [1.5; 14.4] g; p < 0.01) and a larger GC dose at their examination (6.0 [4.0; 8,0] and 5.0 [4.0; 6.0]mg/day, respectively; p = 0.05).

Conclusion. The presence of OP in RA correlates with age, RA duration, articular dysfunction, CRP levels, X-ray change magnitude, hormone therapy duration, and a cumulative GC dose.

The basis for the pathogenesis of rheumatoid arthritis (RA) is an imbalance in the production of proinflammatory and anti-inflammatory cytokines, which may favor the development of systemic manifestations, interstitial lung injury (ILI) in particular.

Objective: to study cytokine concentrations in RA patients with and without ILI.

Subjects and methods. The investigation enrolled three groups. Group 1 included 20 RA patients with ILI; Group 2 comprised 30 RA patients without ILI and Group 3 consisted of 28 healthy donors. All the RA inpatients were treated at the V.A. Nasonova Research Institute of Rheumatology. The diagnosis of RA was made on the basis of the 1987
American College of Rheumatology (ACR) criteria. The serum concentrations of 27 cytokines were determined utilizing multiplex xMAP technology with a Bio-Plex200 analyzer (Bio-Rad, USA). Lung computed tomography (CT) with a GE Light Speed VCT spiral CT scanner (with a section thickness of 0.65 mm) was carried out to detect ILI.

Results. As compared with the healthy donors, the RA patients with and without ILI were observed to have significantly elevated concentrations of interleukin 5 (IL-5), IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-15, eotaxin, granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, interferon-γ (IFN-γ), macrophage inflammatory protein-1β, platelet-derived growth factor BB, RANTES, and tumor necrosis factor-α. In the RA patients with ILI, the concentrations of IL-4 and IFN-γ-inducible protein proved to be higher than in the other
groups; however, these differences reached statistical significance compared to only the healthy donors (p = 0.04 and p = 0.001, respectively). The RA patients with ILI were found to have a significant increase in IL-10 and IFN-γ levels as compared to those without ILI and the healthy donors (p = 0.008 and p = 0.0003; p = 0.0001 and p = 0.0001, respectively). Vascular endothelial growth factor concentrations were found to be lower in the RA patients with ILI than in the healthy donors (p = 0.05).

Conclusion. The RA patients with ILI show a predominance of a Th2 immune response. The found activation of humoral antigen-specific immune response regulators, such as IL-4, IL-5, IL-6, IL-10, and IFN-γ, substantiates the use of anti-B-cell therapy for this type of the disease.

Objective: to provide the clinical characteristics of joint injury in patients with calcium pyrophosphate crystal (CPC) deposition disease.

Subjects and methods. The trial enrolled 68 patients (43 women, 25 men) with a verified diagnosis of CPC deposition disease. Their mean age was 60.2±11.8 years and disease duration was 7.5±6.4 years. Examination revealed the presence of arthritis and arthralgias. Polarizing microscopy with an Olympus CX31-P compensator was used to detect
crystals in synovial fluid. X-ray study of the knee joints was performed in the anteroposterior and lateral projections and that of the hand joints was in the frontal projection, Ultrasonography (USG) of the knee and wrist joints was done using a GE Voluson-I transducer.

Results. A concurrence of arthritis and arthralgias was noted in 37 (54%) patients; 24 (36%) patients had arthralgias only; 7 (10%) had arthritis only. Arthritis affecting the knee, wrist, ankle, and first metacarpophalangeal joints was observed in 53, 15, 12, and 6% of cases, respectively. There was acute arthritis in 18% of the patients and chronic arthritis in 39%; the rate of CPC osteoarthrosis was 43%. Joint USG diagnosed knee and wrist joint chondrocalcinosis in 94 and 56% of the patients, respectively. USG could reveal asymptomatic wrist joint chondrocalcinosis significantly more often (in 56 and 17% of the patients, respectively; p = 0.008). Besides, USG could visualize synovitis in the knee joints in 88% of the patients with isolated arthralgias in them and synovitis in the wrinkle joints in 52% of the patients without clinical signs of inflammation in them.

Conclusion. Osteoarthrosis is the most common form of CPC deposition disease. Knee joints in this disease are most frequently involved. Joint USG is of more informative value in detecting chondrocalcinosis than X-ray study; USG can also identify synovitis in the intact joints.

Objective: to assess the clinical and prognostic informative values of SI in patients with SLE.

Subjects and methods. One hundred and forty-six male patients aged 15 to 64 years with a valid diagnosis of SLE who had been followed up for 15 years were assessed. The patients underwent conventional clinical, laboratory, and instrumental investigations using the standard methods of disease activity assessment. SI and SLICC/ACR Damage Index (SDI) were used to characterize the course and outcomes of SLE. The SI and SDI were analyzed in 133, 91, and 63 patients over time at 1, 5, and 10 years of the disease, respectively.

Results. Significant correlations were found between the SI on study inclusion and the indices reflecting the course and activity of SLE. Analysis of changes in SLE indicated that its maximum increase during the first 5 years of the disease was observed in patients aged < 20 years at the onset of SLE. The patients who had SLE concurrent with secondary
antiphospholipid syndrome showed a more marked SI rise than those without these abnormalities. The highest survival rates were noted in patients with an early SI of 0.

Conclusion. SI is a good indicator reflecting the accumulated activity of the disease. It increases with longer disease duration; moreover, its rise may occur at any disease stages. This trend depends on the form of the disease, the time of diagnosis, and the presence of comorbidity. SI correlates well with the activity and damage indices traditionally used in SLE and with the frequency of exacerbations, suggesting that SI may be used as a prognostic marker.

Objective: to compare the clinical manifestations of coxitis with the data of HJ ultrasound study (USS) on inpatient samples.

Subjects and methods. This cross-sectional study enrolled 220 AS patients meeting the modified 1984 New York criteria who had been consecutively admitted to the clinic of the V.A. Nasonova Research Institute of Rheumatology in 2012–2013. A specially designed schedule was filled out for each patient. Disease activity was measured by the BASDAI and ASDAS and functional status was assessed by the BASFI. Coxitis was diagnosed on the basis of clinical signs, such as HJ pain and/or movement limitations on patient admission to the clinic. All the patients underwent HJ USS.

Results. The clinical signs of coxitis were found in 162 (73.6%) patients. In 107 (66%) of them, pain intensity recorded by the digital rating scale if only in one joint was 4 scores or higher. The patients with and without the clinical signs of coxitis were matched for age and disease duration. However, in coxitis, high disease activity was detected significantly more frequently and BASFI scores were also significantly higher. USS indicated that 119 (54%) patients had joint effusion. HJ effusion was found in 104 (63%) of the 162 patients with clinically manifest coxitis; and among the
119 patients with USS verified coxitis, 87% were seen to have clinical signs of joint injury and 104 (47%) patients had both clinical and ultrasound signs of HJ injury simultaneously. USS revealed no signs of synovitis in 58 patients with the clinical signs of HJ lesion.

Conclusion. Among the patients with AS, the rate of coxitis runs to 51%. The patients with coxitis have higher disease activity and more pronounced functional impairments than those without HJ injury. Coxitis causes considerably diminished working ability. In a number of cases, USS allows, when the clinical manifestations are similar, a differential diagnosis between synovitis and enthesitis located in this area. It is necessary to conduct additional studies to specify the upper limit of the normal range for the neck-capsular distance that is to be kept in mind when diagnosing coxitis by USS.

The lecture gives information on the epidemiology and pathogenesis of glucocorticoid-induced osteoporosis (GCOP). It presents the latest diagnostic criteria, a modified FRAX algorithm (assessment of 10-year osteoporotic fracture risk) in relation to the taken dose of glucocorticoids, the data of recent clinical guidelines for the treatment and prevention of GCOP, and the specific features in relation to patient age.

Autoimmune (immunoinflammatory) rheumatic diseases are defined as clinical syndromes whose development is associated with the abnormal activation of T cells, B cells, and many other cells of the immune system, which gives rise to the progressive inflammation and destruction of the viscera. In spite of the high efficiency of combined therapy with biologic agents and standard disease-modifying antirheumatic drugs, primarily methotrexate, less than half of patients with rheumatoid arthritis (RA) could achieve a significant clinical effect and, very rarely, sustained remission. The combined influence of genetic and environmental factors may lead to loss of immunological tolerance, the basis for which is an imbalance between the effector and regulatory components of the immune system. To restore tolerance without chronic nonspecific immunosuppression observed in the use of majority of current anti-inflammatory drugs (including GEBAs) is regarded as the most important task of pharmacotherapy for RA. The aim of the review is to discuss firstly the role of the so-called T regulatory (Treg) cells as one of the critical components for the maintenance of tolerance and secondly promises for the pharmacotherapy of RA associated with the correction of the functional activity of Treg cells.

The literature review presents the current idea about the mechanisms of chronic pain. Experimental and clinical studies of the mechanism of chronic pain in osteoarthrosis (OA), which show that dysfunction of pain systems themselves (the so-called dysfunctional pain) along with the nociceptive mechanisms caused by chronic inflammation and degenerative changes in the joint area plays an important role in the chronization of pain syndrome, are considered in detail. Identification of the dysfunctional mechanisms of chronic pain in OA allows an understanding of the dissociations existing between the intensity of pain and the degree of structural changes in the joint. The paper also attempts to detect comorbidities that may be additionally involved in the development of pain. Effective ways to treat OA are outlined.

Systemic lupus erythematosus (SLE) has been a central preoccupation of modern-day investigators for many years due to the chronic progressive course of the disease with frequently irreversible involvement of different organs and systems and to high death rates. Despite the notable advance made in the diagnosis and therapy of SLE, which has ensured longer survival, the quality of life in patients remains worse than the population level. At the moment, quality of life along with other parameters should be taken into account when comprehensively examining the patients with SLE.

Rheumatoid arthritis (RA) is an autoimmune disease with erosive and destructive polyarthritis and systemic manifestations. Pulmonary involvement (PI) is common in RA. With high-resolution computed tomography, the detection rate of PI in RA is as high as 50%. PI is a direct cause of death in 10–20% of patients with RA. Autoimmune mechanisms play a leading part in the development of PI in RA. Under the hypothesis advanced by M. Selman et al., that impaired alveolocyte regeneration processes after injury rather inflammation underlie the pathogenesis of pulmonary fibrosis. The pathological process is triggered by damaged alveolocytes and characterized by the migration and proliferation of fibroblasts and myofibroblasts, the suppressed apoptosis of the latter, and the enhanced activity of pneumofibrosis-stimulating cytokines. This gives rise to remodeling of the extracellular matrix, including destruction of the basement membrane, angiogenesis, and fibrosis. The paper considers the types of lung injury in RA and main methods for diagnosis and therapy.

Systemic scleroderma (SSD) is a clinically heterogeneous disease characterized by obliterating microangiopathy, autoimmune activation, and fibrosis of the skin and viscera. Interstitial lung fibrosis (ILF) is a characteristic visceral injury in SSD and considered to be a main cause of disability and death. The diagnosis of SSD-associated ILF is made on the basis of a cluster of symptoms, physical examination, external respiratory function changes, and high-resolution computed tomography. Pulmonary fibrosis is included in the 1980 American College of Rheumatology (ACR) classification criteria and in the joint ACR and 2013 European League against Rheumatism diagnostic criteria. According to the definition given in these criteria, pulmonary fibrosis in SSD is
described as bilateral changes, most pronounced in the basal lung segments, which are not a sign of primary lung disease. The paper describes a case of a SSD patient with a complete spectrum of characteristic signs of unilateral pulmonary fibrosis. This case is the first description of unilateral ILF in SSD and shows the need for ruling out
connective tissue diseases, primarily SSD, when such lung changes concurrent with extrapulmonary manifestations are detected.

The material is a continuation of the discussion initiated in this journal No. 2, 2014 and caused by the paper «Early diagnosis of ankylosing spondylitis» (No. 4, 2013). Opponents' commentaries on the elaboration and modification of classification criteria are successively considered and commented; much attention is given to the problem of terminology.