When dactylitis is detected in a patient with psoriatic arthritis (PsA), it is necessary to use active treatment as soon as possible, since in the absence of therapy the disease progresses to joint erosion and  functional disorders. The paper considers the clinical signs and  diagnosis of PsA and notes the importance of differential diagnosis in this sign with other joint inflammatory diseases. It points to the  necessity of elaborating common approaches to an objective  assessment of the severity of dactylitis. Its immunopathogenesis and main treatment areas, including the use of biological agents (BAs),  are detailed. There are data of clinical trials that have evaluated the  efficiency of treatment for dactylitis and established that in most  cases, the use of BAs considerably reduce not only the severity of its clinical signs, but also concomitant bone marrow edema. It is noted  that the development of new pathogenetic treatments targeting a number of currently established biologically active molecules that  play an important role in the pathogenesis of dactylitis will enhance  the efficiency of treatment in patients with PsA.

Extraskeletal manifestations (ESMs) are commonly observed in ankylosing spondylitis (AS). The available data on the association of ESMs with the inflammatory activity and other clinical parameters of AS are contradictory.

Objective: to assess the association of ESMs with the inflammatory activity and other manifestations of AS.

Patients and methods. The investigators of the V.A. Nasonova Research Institute of Rheumatology examined a total of 452 patients (363 men and 89 women) diagnosed with AS meeting the New-York  criteria (1984). The patients' median age was 31.5 [24; 41] years;  median disease onset age, 19.5 [15; 23] years; and disease duration, 11.5 [7; 18] years. HLA B27 was identified in 442 (97.7%) patients. In addition to standard laboratory and instrumental  examinations, 172 patients underwent transthoracic echocardiography; Rehberg's test, if indicated; IgA test; histological  examination of subcutaneous fat tissue or duodenal mucosa for  amyloid; renal ultrasound; colonoscopy; and consultations by an ophthalmologist, a dermatologist, a nephrologist, an urologist,  and a gastroenterologist. Uveitis, cardiac involvement (cardiac conduction disturbance, aortic and valvular changes), inflammatory bowel disease (IBD), glomerulonephritis, and psoriasis were  considered to be ESMs. The latter were detected in 218 (48%) of the 452 patients; there was uveitis in 140 (30%), cardiac conduction  disturbance in 61 (13.4%), psoriasis in 17 (3.7%), IBD in 16  (3.5%), nephritis in 16 (3.5%), and aortic and valvular changes in 71 (41.2%) of the 172 patients. The groups of patients with ESM (n  = 218) and without ESM (n=234) were compared with regard to the  onset age of AS, the presence of HLA- 27, peripheral arthritis,  coxitis, enthesitis, syndesmophytis, fever, anemia, the need for biological agents (BAs) and/or systemic glucocorticoids (GCs), Bath  Ankylosing Spondylitis Disease Activity Index (BASDAI), and  erythrocyte sedimentation rate (ESR). 

Results. The ESM and non-ESM groups were matched for gender, age, duration of AS, and the presence of HLA-В27. No significant differences were found in ESR, BASDAI, and the frequency of coxitis, enthesitis, and syndesmophytis in the spine. The ESM group versus non-ESM group was significantly more frequently observed to have peripheral arthritis in 148 (67.8%) of the 218 patients and in 70  (33.2%) of the 234 patients, respectively (p<0.0001); fever in 34  (15.6%) and 12 (5.1%), respectively (p<0.0001), anemia in 58  (26.6%) and 26 (11.1%), respectively (p<0.0001); GAs and/or  systemic GCs were taken by 121 (55.5%) and 58 (24.8%) patients, respectively (p<0.0001).

Conclusion. ESMs in patients with AS are associated with peripheral arthritis and inflammatory activity indicators.

Anterior uveitis (AU) and ankylosing spondylitis (AS) are associated with histocompatibility human leukocyte antigen (HLA)-B27. Previous genetic studies conducted in different populations have also demonstrated other genetic associations, including HLA, both  general and individual ones for AU and AS.

Objective: to investigate the association of HLA class I with AU depending on the presence or absence of spondyloarthritis (SpA).

Patients and methods. The investigators used the data of HLA class I typing in the patients referred by ophthalmologists for examination to the V.A. Nasonova Research Institute of  Rheumatology, as well as the previous databases of patients with  AS. The investigation included retrospectively two groups of patients with AU: 1) 52 patients with a confirmed diagnosis of SpA (AU + SpA); 2) 96 patients who had other types of AU (idiopathic AU  (n=52), viral uveitis (n=29), multiple sclerosis (n=2) toxoplasmosis  (n=2), sarcoidosis (n=1), tuberculosis (n=1), chlamydiasis (n=3),  Behcet's disease (n=2), juvenile chronic arthritis (n=3), and Fuchs'  heterochromic cyclitis (n=1). A control group consisted of 150 healthy test donors. The distribution of HLA class I (A, B, and Cw) was analyzed when comparing the two groups of patients with AU and each control patient group.

Results. HLA-B27 was detected in 96.1% of cases in the AU + SpA group, in 40.6% in the AU group, and in 7.3% in the controls. In HLA-27-positive patients, the risk (odds ratio (OR) for joint disease  (AU + SpA) was 315.9 (95% confidence interval (CI), 61.9–2176.7); p<0.0000001; the risk for AU was 8.7 (95% CI, 3.9–19.4);  p<0.000001. The HLA-C-locus antigens showed a high incidence of  Cw2 antigen in patients with AU + SpA and in those with AU compared to the controls (64.0, 36.3, and 10.0%, respectively): AU + SpA versus the controls (p<0.000001), AU versus the controls  (p<0.00001). In the two groups of patients with a high HLA-B27  frequency, this substantially higher rate of Cw2 antigen carriage was  natural due to the non-equilibrium coupling phenomenon, including  that for B27 and Cw2 antigens. The rate of Cw7 antigen was significantly lower in the AU + SpA group versus the controls: 12.8 and 38.7% (p=0.002). In the group of AU patients without SpA, the rate of this antigen did not differ significantly from that in the control and AU + SpA groups.

Conclusion. The analysis of the distribution of HLA class I confirmed the association of B27 antigen with AU in the Russian population. There were no associations with other antigens other than Cw2. Cw7 antigen can play a protective role against SpA, since the frequency  of this gene was not lower in AU patients compared to the controls.

The development of atherosclerosis is a complex multifactorial process, in which the markers of bone formation and resorption play an important role and which is closely related to the calcification of the vessel intima and fibrous plaques.

Objective: to assess the relationship between bone remodeling markers (cathepsin K, C-terminal telopeptide of type I collagen (CTX-I) and osteopontin), bone mineral density (BMD), and severity of coronary atherosclerosis in men with stable coronary heart disease (CHD).

Patients and methods. The investigation enrolled 102 male patients with verified stable CHD. Coronary angiographic and densitometric findings and blood cathepsin K, osteopontin, and CTX-I concentrations were assessed.

Results.The concentration of cathepsin K and CTX-I was significantly higher and that of osteopontin was significantly lower in patients with CHD than in men without CHD. There was no association of the level of bone remodeling markers with the type of coronary artery lesion and the severity of coronary atherosclerosis. Cathepsin K concentrations in patients with a high SYNTAX score of coronary atherosclerosis were shown to be 5.5 times lower in the presence of osteopenic syndrome (OPS) than in those with the similar severity of atherosclerosis and normal BMD. Analysis of osteopontin and CTX-I levels from the standpoint of the presence of OPS suggests that there are no differences in relation to both the type of coronary vessel lesion and its severity.

Conclusion. Current data suggest that there are common mechanisms for the development of two socially significant conditions: atherosclerosis and osteoporosis (OP). The phenomenon of concomitant development of these diseases has been studied mainly in postmenopausal women. Today, however, OP is also increasingly found in men, associating with more severe manifestations of coronary atherosclerosis than in patients with no signs of osteopenia.

The widespread use of parenteral chondroprotectors is a feature of Russian medical practice. There are many drugs of this series in a Russian physician's arsenal, including chondroitin sulfate (CS),  glucosamine sulfate (GS), glycosaminoglycan-peptide complex, and  bioactive concentrate from small sea fish for intramuscular  injections. The paper analyzes Russian trials of the efficacy and  safety of two injectable formulations of CS and GS (ICS and IGS).  ICS was tested in 17 articles containing a total of 1639 patients with  osteoarthritis (OA), non-specific back pain (NBP), or shoulder  fractures and pain after stroke. Standard therapy (NSAIDs +  physiotherapy) served as a control in the majority of the paper. In  these trials, the reductions in visual analog scale (VAS) and WOMAC pain in OA treated with ICS averaged 58.2±22.3% and those were 26.1±14.7% in the control groups; the reductions in VAS NBP  reached an average of 87.1±16.8 and 62.2±21.7%, respectively.  ICS also showed a good effect in shoulder fractures and pain after a  stroke. The number of local adverse reactions after injections was  insignificant (4.4%); they did not threaten the health of patients and they caused ICS to be discontinued only in 3 cases. IGS was  investigated in two trials (n=154), which confirmed its efficacy (total pain relief >50%) and relative safety. Thus, the data of Russian trials suggest that ICS and IGS have good therapeutic potential and favorable tolerance.

Psoriatic arthritis (PsA) is a chronic inflammatory disease of the joints, spine, and entheses, which is associated with psoriasis. The pathological process is localized mainly in the tissues of the  locomotor system and leads to the development of erosive arthritis  and intra-articular osteolysis. PsA occurs in 5–7% of patients with  moderate psoriasis. Despite advances in the treatment of psoriasis  and PsA with diseasemodifying antirheumatic drugs (DMARDs) and  biological agents (BAs), the problems associated with  immunogenicity, infectious complications, and secondary inefficiency  have not been fully solved. These factors have motivated the search  for novel targeted synthetic drugs (signaling pathway inhibitors).  This group of drugs includes apremilast, a phosphodiesterase 4  inhibitor. Recent data of controlled studies suggest that the drug is effective and safe in treating psoriasis and PsA. Prospects for the use of apremilast in PsA are associated with the possibility to use the drug in patients because of the inefficacy of DMARDs or BAs and  with the ability to maintain long-term (more than 3-year) remission  and to reduce the manifestations of enthesitis and dactylitis.

Lower respiratory tract infections occupy a leading place in patients with rheumatic diseases (RDs). Pneumococcus (S. pneumoniae) remains the most common causative pathogen of pneumonias in  both the general population and patients with RDs. This review gives the frequency and risk factors of pneumonias in different RDs. It  presents the main clinical characteristics and approaches to treating  and preventing pneumonias due to various (including opportunistic)  infections. The problem of pneumonias is very relevant in patients  with RDs and it has been simultaneously extremely little developed – there are single publications on this problem are available in the  Russian literature. There is a need for further investigations of its  various aspects (including the efficiency of and safety of vaccination) in Russia within the uniform science program, which will make it  possible to develop clinical guidelines for the management of these patients.

The main goal of treatment for rheumatoid arthritis (RA) is to suppress inflammation using basic and symptomatic therapies. At the same time, the above strategy does not significantly stop joint  destruction that leads to disability in patients. The review analyzes  publications dealing with a search for intercellular interaction  regulators among the main effector cells in the pannus – fibroblast- like synoviocytes (FLSs). It assesses the influence of FLS aggression  factors on invasive pannus behavior, the possibility of their targeted deactivation during biological therapy, and the preliminary  results of similar treatment by the examples of animal models. It is  shown that the most promising targets for biological therapy may be FLS adhesion molecules, such as transmembrane receptor cadherin  11, integrins α5/β1, and VCAM1, ICAM1, which actively participate in the attachment of FLSs to the cartilage surface and activate their production of cytokines, growth factors and aggression factors.

Numerous epidemiological surveys may suggest that there is a relationship between chronic kidney disease (CKD) and asymptomatic hyperuricemia; at the same time there is growing  evidence that elevated uric acid (UA) is the cause of kidney injury.  The possible mechanisms of CKD in hyperuricemia are said to be  immune inflammation that is both mediated by UA crystallization and independent from the latter; the impact on the activity of the renin- angiotensin-aldosterone system. The currently available optimistic  data on the efficiency of drug correction of hyperuricemia at different stages of CKD are justified primarily by the long-term use of  xanthine oxidase inhibitors (allopurinol, febuxostat) and allow urate- lowering therapy to be regarded as potentially nephroprotective. At  the same time, further large-scale randomized controlled studies are needed to confirm this finding.

The high anti-inflammatory activity and pronounced analgesic effect of nonsteroidal anti-inflammatory drugs ((NSAIDs) allow successful treatment for pain syndrome associated with many diseases, primarily rheumatic diseases. NSAIDs are the main agents used to relieve pain in osteoarthritis, lower back pain, and  periarticular soft tissue diseases. They are also an essential  component of combination pharmacotherapy for chronic arthritis.  The therapeutic effect of NSAIDs is determined by the suppressed  activity of the cyclooxygenase (COX) isoenzymes COX- 1 and COX-2. The widely use of NSAIDs in clinical practice is considerably limited by the risk of adverse reactions (ARs) in the gastrointestinal tract  (GIT), which are characteristic for this class of drugs. Medications  that are able to selectively inhibit the activity of COX-2 while  maintaining that of COX-1 less rarely cause ARs in GIT. This selective effect is produced by aceclofenac. A number of clinical trials have demonstrated the high efficacy of this drug in treating various  locomotor diseases. The drug has been also noted to be well  tolerated: the risk for aceclofenac- induced ARs in GIT is  substantially lower than that due to the use of the majority of other NSAIDs.

Due to the development of synovitis, early-stage hand osteoarthritis (HOA) mimics hand joint injury in rheumatoid arthritis (RA). However, the topography of synovitis is diverse in these diseases:  distal interphalangeal and thumb joints are involved in the process in HOA. In the latter, tests are negative for immunological markers  (anti-cyclic citrullinated peptide antibodies), which is typical of RA.  The differences between HOA and RA are prominent, as evidenced  by hand X-rays and magnetic resonance imaging. Investigations  suggest that cytokine profile imbalance is implicated in the  pathogenesis of osteoarthritis, which brings it closer to RA. However, therapy for HOA has not been practically developed; there are only a few works on the use of disease-modifying antirheumatic drugs and  biological agents in these patients. It is necessary to work out Russian guidelines for the treatment of HOA.

Autoinflammatory diseases (AIDs) are a heterogeneous group of rare genetically determined, hereditary conditions characterized by unprovoked inflammatory episodes that are manifested by recurrent  fever and clinical symptoms reminiscent of rheumatic manifestations in the absence of autoimmune or infectious causes. The prevalence of hereditary AIDs in the population tends to increase. The list of AIDs is quite wide and includes various groups of diseases, including  those faced by not only a pediatrician, but also by an adult  rheumatology specialist. Practitioners do not know much about  hereditary AIDs, so the latter are often diagnosed late. However, due to the clinical introduction of new diagnostic techniques, primarily  genetic ones, and drug therapy in the detection and treatment of  these diseases, there has been clear progress, which makes it possible to change long-term prognosis in AIDs and to arouse increasing interest in the diseases not only among pediatricians, geneticists, but also among rheumatologists and general practitioners.

Adverse reactions (ARs) are the reverse side of successful pharmacotherapy for human diseases. Unfortunately, many drugs, which are able to stop disease progression and reduce patient suffering, in some cases cause serious complications that pose a  serious threat to health and life. This problem has two aspects: medical  and legal. This paper proposes to analyze three clinical cases related to  serious ARs from the use of the most popular class of pain killers –  nonsteroidal anti-inflammatory drugs. Each case is considered from the  point of view of a medical expert and a lawyer.

The problem of managing reproductive-aged patients (primarily women) with inflammatory diseases is becoming more and more relevant in recent years. It was the objective of the symposium held  during the Annual Scientific and Practical Conference of the V.A.  Nasonova Research Institute of Rheumatology on Early-Stage  Rheumatic Diseases: Scientific Advances and Clinical Practice, at  which leading Russian rheumatologists, gastroenterologists and  gynecologists spoke. The Symposium noted that the current level of  development of medicine allows many reproductive-aged women  suffering from rheumatic diseases, inflammatory bowel diseases,  etc. to well bear and give birth to healthy children. This is achieved  due to the effective control of disease activity, which in turn results  from both the current effective therapeutic tactics and the trusting interaction between the attending physician and the female patient.