The paper presents the new version of the clinical guidelines «Rational use of nonsteroidal anti-inflammatory drugs (NSAIDs) in clinical practice » prepared by the Association of Rheumatologists of Russia, the Russian Pain Society, the Russian Gastroenterological Association, the Russian Society of Cardiology, the Association of Traumatologists and Orthopedists of Russia, the Association of Interdisciplinary Medicine, and the Russian Association of Palliative Medicine.

In our country, NSAIDs are the most important and most popular class of analgesics. Unlike global practice, Russian physicians rather rarely recommend paracetamol as a first-line drug to relieve moderate or severe pain, by giving preference to NSAIDs; the use of opioid analgesics for noncancers is minimized because of tight legal restrictions.

NSAIDs are effective and easy-to-use; however, they are far from safe; the administration of these medications may lead to serious gastrointestinal, cardiovascular, renal, and other complications in a number of cases. So the use of NSAIDs should be compulsorily monitored for adverse reactions and the choice of a specific drug for each clinical case should be based on the objective estimation of a ratio of its efficacy to safety.

In recent years, there have been fresh data on the use of NSAIDs for different diseases and a few novel representatives of this drug group have appeared on the Russian pharmacological market.

This all has necessitated a new version of the guidelines on the rational use of NSAIDs. These are based on the provisions that have high validity and have been confirmed by the results of well-organized clinical and large-scale population-based studies, as well as by their meta-analysis.

The guidelines are intended for physicians of all specialties.

A large number of classification criteria for spondyloarthritis (SpA) are simultaneously used in modern rheumatology in the almost complete absence of diagnostic criteria. This poses a number of problems, among which there are two most important ones: 1) the frequent use of classification criteria to make a diagnosis in real clinical practice; 2) the possibility of stating different nosological entities of SpA in one patient in the presence of the same clinical picture.

Objective: to investigate the specific features of the diagnosis of SpA and the use of its classification criteria in clinical practice.

Subjects and methods. The investigation enrolled 119 patients with the established diagnosis of ankylosing spondylitis (AS), psoriatic arthritis (PsA), undifferentiated axial or peripheral SpA. Whether their clinical picture complied with the modified New York criteria, the European Spondyloarthropathy Study Group (ESSG) criteria, the Amor criteria, and the Assessment of Spondyloarthritis International Society (ASAS) classification criteria for axial and peripheral SpA and whether the Russian version of the modified New York criteria complied with the Classification criteria of Psoriatic ARthritis (CASPAR) were determined in the patients.

Results. Sixty-three patients diagnosed with AS (M45), 44 with PsA (M07.0-07.3), 8 with undifferentiated SpA (M46.9), and 4 with nonradiographic axial SpA (M46.8) were followed up by attending physicians. The latter diagnosed AS in 10 patients who met the ASAS criteria for axial PsA but not the modified New York criteria. Twenty-one patients diagnosed as having PsA simultaneously met both the CASPAR criteria and the modified New York criteria, which could establish the diagnosis of AS in these cases. Eighty-one (68.0%) out of the 119 patients met the Amor criteria; 98 (82.3%) patients, the ESSG criteria; 91 (76.5%), the ASAS criteria for axial SpA; 18 (15.1%), the ASAS criteria for peripheral SpA; 76 (63.8%), the modified New York criteria; 88 (73.9%), the Russian version of the modified New York criteria; 42 (32.3%), the CASPAR criteria. No intersection of criteria was observed in only 5 patients; 113 (94.9%) patients met ≥2 criteria; 96 (80.7%), ≥3 criteria; 81 (68.1%), ≥4 criteria; 66 (55.5%), simultaneously ≥5 criteria; and 18 (15.1%), simultaneously 6 criteria.

Conclusion. Most patients with SpA meet ≥2 classification criteria, which gives the chance to state ≥2 nosological entities in the same patient. This demonstrates the elaboration of diagnostic criteria that can make a clear distinction between different forms of SpA in clinical practice.

Objective: to study bone mineral density (BMD) of the lumbar spine (LS) and femoral neck (FN) in patients with early axial spondyloarthritis (SpA) and to reveal its association with inflammatory disease activity.

Subjects and methods. Seventy-three patients aged 18–45 years with inflammatory back pain lasting at least 3 months and not more than 5 years were examined. Axial SpA was diagnosed according to the 2009 ASAS criteria. BASDAI and ASDAS C-reactive protein (CRP) values were used to estimate disease activity; BASFI was employed to evaluate functional status. The examination encompassed determination of HLA-B27, X-ray of the pelvis and LS, magnetic resonance imaging (MRI) of sacroiliac joints, LS, and hip joints (in the presence of clinical signs of their injuries), densitometry of LS (LI-IV) and FN. By taking into account the young age of patients, the Z-score was applied to measure BMD. The latter is considered lower if the Z-score is 1–2 standard deviations (SD) in at least one of the segments under study.

Results. The median Z-score was -0.7 (-1.3; -0.3) SD for FN and 0.9 (-1.6; -0.5) SD for LS. Reduced BMD in at least one of the segments under study was detected in 13 (17.8%) patients: that in LS and FN in 11 (15.1%) and 5 (6.8%) patients, respectively. Lower BMD was observed in two segments in 3 (4.1%) patients. No association was found between lower BMD and age, gender, disease activity (BASDAI, ASDAS), and laboratory inflammatory markers (erythrocyte sedimentation rate (ESR) and CRP). A relationship was established between inflammatory changes according to the data of MRI of LS (MRI spondylitis) and reduced BMD in the same segment. MRI spondylitis was detected in 8 patients. Five and 3 patients with spondylitis of LS were found to have lower and normal BMD in this segment, respectively. Six out of 65 patients without MRI spondylitis in LS had its reduced BMD and the remaining (n=59) patients had its normal BMD (p=0.0014).

Conclusion. There was an association between the active inflammatory changes as evidenced by LS MRI and the reduced BMD in this segment of the axial skeleton. Our data validate the hypothesis that in early axial SpA, bone is lost in the vertebral bodies due to local inflammation.

The increasing number of women with ankylosing spondyloarthritis (SpA) makes it relevant to study the specific features of this disease in persons of different genders.

Objective: to study the indicators of activity and functional status in male and female patients with axial SpA.

Subjects and methods. The study enrolled 91 patients (43 women and 48 men) with axial SpA admitted to the Rheumatology Unit of the Saratov Regional Clinical Hospital in 2013. The age of the women and men was 41.63±12.04 and 41.94±12.76 years, respectively. All the patients fulfilled the ASAS criteria for axial SpA. 60.43% of the patients had ankylosing spondylitis (AS) meeting the modified New York criteria; 26.37% had psoriatic arthritis (PsA) according to the CASPAR criteria (only patients with axial involvement were included in the study and those with peripheral arthritis were excluded); 9.89% had undifferentiated axial SpA. Age at symptom onset, disease duration, and age at diagnosis of axial SpA were taken into account. The activity of axial SpA (ASDAS, BASDAI, highsensitivity C-reactive protein) and the mobility of the axial skeleton (BASMI and its components) were investigated in patients of different genders.

Results. The study has established that the women are hospitalized with diagnosed axial SpA as often as the men. The indicators of activity and axial skeleton mobility are similar in the male and female patients with axial SpA as a whole and with a disease history of less than 10 years. Having a disease history of more than 10 years, the women preserve greater mobility of the lumbar and cervical spine than do the men with the similar disease activity.

Objective: to study the rate and pattern of comorbidities in two groups of patients with rheumatoid arthritis (RA) in different follow-up years.

Subjects and methods. The pattern of comorbidity was investigated in RA patients treated at the Rheumatology Unit, Saratov Regional Clinical Hospital, in different follow-up years. The investigation enrolled patients treated with disease-modifying antirheumatic drugs (DMARDs) in a stable dose for 3 months or longer. The patients were interviewed and objectively examined and the data of their outpatient medical records were taken into consideration. Group included 201 patients examined in 2006–2007. Group 2 comprised 328 patients examined in 2012–2013.

Results. Comorbidities were ascertained in 67.2% of the patients in Group 1 and in 86.6% of those in Group 2. Two to five co-occurring diseases were more common in the examinees in 2012–2013 (66.9%) than in those in 2006–2007 (57%). The patients of both groups were most frequently found to have hypertension (60 and 57.7% of the patients, respectively) and osteoarthritis (OA) (71.1 and 50.7%). Out of the other diseases, the patients were most commonly found to have gastrointestinal tract (GIT) diseases (97.8 and 80.3%, respectively) and urinary tract infections (22.4% and 19.7%).

Conclusion. The rate of comorbidities remains high in patients with RA. Among the comorbid diseases, there is a preponderance of hypertension, GIT diseases, and OA.

The paper describes the case of a female patient who had at least three diseases: scleromyxedema, dermatomyositis/polymyositis (DM/PM), and paraproteinemia (monoclonal gammopathy). The concurrence of these diseases determines the atypism of their clinical and morphological patterns, as well as refractoriness to performed therapy. Scleromyxedema preceded DM followed by paraproteinemia, which does not rule out its presence in an earlier period when the patent was not carefully examined. The specific feature of this case is scleromyxedema concurrent with DM that was prevalent in the clinical picture of the disease, by determining the severity of the patient’s status and the need to be treated with high-dose glucocorticoids in combination with immunosuppressive drugs. There was no evidence for scleroderma systematica that was supposed to be present in the patient who had scleroderma-like skin involvement.

The authors have repeatedly mentioned the concurrency pattern of scleroderma diseases, which reflects the close mechanisms of their development and hinders the identification of specific nosological entities. In this observation, the concurrence of scleromyxedema and DM complements a group of overlap diseases observed in dermatology and rheumatology.

Paraproteinemia characteristic of scleromyxedema is occasionally encountered in systemic connective tissue diseases. The patient had monoclonal gammopathy that is most common in scleromyxedema. No signs of myeloma and tumors were seen. Classical paraneoplastic DM/PM was not detected either, which does not rule out the fact that the mechanism responsible for the development of this syndrome and the disease is similar in the patient described.

Autoinflammatory syndromes (AISs) are a heterogeneous group of genetically determined diseases, whose basis is the dysregulated mechanisms of inflammation. Despite the fact that traditional primary immunodeficiencies and AISs have an external dissimilarity, there are many parallels, such as hypodiagnosis, multisystem pattern of lesion, chronic inflammation-induced complications, possible medical therapy using cytokine inhibitors, and cardinal cure by stem cell transplantation and gene therapy.

There are more than 25 different AISs, their common manifestations are fever episodes accompanied by laboratory inflammatory activity, polymorphous eruption, lymphoproliferative syndrome, and injury to different organs.

Genetic analysis plays an important role in the diagnosis in traditional AISs and primary immunodeficiencies. This is particularly relevant to AISs that are not infrequently very closely allied phenotypically. Moreover, it is important that the detection of a causative genetic defect frequently determines man-agement tactics for patients.

For AIS treatment, there is a spectrum of agents modulating these or those inflammatory components. However, there is a problem of resistance to standard therapy as before. Pathogenetic therapy for AISs is lifetime, expensive, and commonly responsible for serious adverse reactions, which worsens quality of life in patients. Patients with AISs, like those with other primary immunodeficiencies, need a multidisciplinary approach with the participation of various specialists. These patients should be followed up in specialized centers that perform treatments according to the international algorithms. Since the early diagnosis of primary immunodeficiencies and AISs is a key to their successful treatment; primary care physician’s awareness of these rare diseases is of the most importance.

Macrophage activation syndrome (MAS) is a severe life-threatening complication presenting with hemophagocytosis, pancytopenia, coagulopathy, and liver and CNS dysfunctions. The disease belongs to a group of histiocytic disorders. The common triggers for MAS are rheumatic diseases, particularly systemic juvenile idiopathic arthritis (SJIA), infectious diseases, immunodeficiency, and medication. The paper describes the main stages of the pathogenesis of MAS and the role of hypercytokinemia. It presents the clinical picture of MAS and hemophagocytic lymphohistiocytoses. The evolution of diagnostic approaches to diagnosing MAS and related conditions, such as hereditary and secondary hemophagocytic lymphohistiocytosis, is considered. It is shown that it is important to elaborate diagnostic criteria for patients with SJIA. Main current approaches to therapy for MAS are outlined.

Tumor necrosis factor (TNF) receptor-1-associated periodic syndrome (TRAPS) is a classical autoinflammatory syndrome (AIS). The paper describes repeated cases of TRAPS in an ethnic Russian family. Molecular genetic examination of a 9-year-old boy, his mother and his grandmother has revealed the heterozygous mutation of c151C<T in exon 2 of the TNFRSF1 gene, which gives rise to amino acid substitution in pHis51Tyr protein sequencing. It is interesting that this mutation has been described in a North American population, but it has been encountered in only 2% of the patients with TRAPS in the European Registry (EuroTRAPS). This case alludes to the fact that in the Russian population there are families with TRAPS, which may have atypical mutations in the TNFRSF1A gene. Curiously, his mother and his grandmother were diagnosed with TRAPS only after its identification in the child (i. e. 34 and 45 years after the onset of the disease, respectively). Moreover, maternal blood tests permanently showed a pronounced increase in the acute-phase inflammatory markers missed by their local doctors. With each further generation, the family has exhibited an early onset of TRAPS and its progressively severer course with more time taken for its attacks. But if his mother and his grandmother had symptoms as erythema centrifugum, fasciitis, myalgias, and transient joint contractures, which are a distinguishing feature of this syndrome, the manifestations of the disease in the child were more non-specific. In the patient’s mother, the abovementioned characteristic symptoms of TRAPS occurred not at the onset of the disease, but just in adolescence. It is not inconceivable that if her son had not been adequately treated, he could also develop these symptoms with time. It is intriguing that the child was observed to have clinical hemorrhagic vasculitis, a condition associated with a number of AISs, primarily with familial Mediterranean fever. In this case, all the manifestations of the disease, including hemorrhagic vasculitis, were completely abolished in the child treated with the interleukin 1 inhibitor canakinumab.

Muckle-Wells syndrome (MWS) is an autoinflammatory disease belonging to a group of cryopyrin-associated periodic syndromes (CAPS). It is considered to be one of the intermediately severe conditions among CAPSs and to be intermediate between the severest syndrome – Chronic I nfantile Onset Neurologic Cutneous Articular/Neonatal Onset Multisystem Inflammatory Disease (CINCA/NOMID) and the mildest syndrome–Familial Cold Autoinflammatory Syndrome (FCAS). MWS, like all cryopyrinopathies, is caused by a mutation in the NLRP3 (CIAS1) gene; it shows an autosomal inheritance pattern. There are reports on familial MWS cases in the foreign literature; such examples are sporadic in Russia. The given clinical observation clearly demonstrates a genetically verified familial case of MWS in a mother and her daughter in a Russian population and shows how long (occasionally during tens of years or more) the complete complex of the disease may be formed. The results of treatment with the interleukin-1 inhibitor canakinumab in both patients are also given. The high good tolerability and high efficacy of the drug against the clinical manifestations of MWS and acute-phase markers are shown.

The paper summarizes the data of a randomized placebo-controlled phase 3 GO-RAISE trial of spondylitis (AS) patients receiving two different doses (50 and 100 mg) of golimumab (GLM), which evaluates its efficiency and safety and X-ray progression of changes in the axial skeleton. In AS patients, GLM therapy leads to a rapid long-lasting clinical and radiological response. The tolerability of long-term therapy with GLM generally complies with the safety profile of the entire class of tumor necrosis factor-р (TNF-р) inhibitors.

The data of the GO-RAISE trial has substantiated once again the established fact that the high baseline level of C-reactive protein (CRP) and the presence of syndesmophytes are predictors for a rapider X-ray progression. At the same time, the results of the trial may question the recent assumptions that TNF-р suppression can exert a stimulating effect on the formation of new bone tissue with time. Further studies are to determine whether there is an association between the presence of syndesmophytes and elevated CRP levels and whether they have a combined effect on X-ray progression, and if so, whether the development of structural changes may be prevented with TNF-р inhibitors to be used at the earlier stages of the disease.

In clinical practice, intra-articular injections of glucocorticoids (GC) are widely used to treat chronic joint inflammatory diseases, osteoarthritis (OA), and extra-articular soft tissue involve-ment. GCs given to patients with chronic arthritis may rapidly suppress joint inflammatory changes and ensure significant clinical improvements well before there is a benefit of prescribed disease-modifying antirheumatic drugs. According to the clinical features of disease, GCs may be used for systemic or local treatment in each specific case and a combination of these two treatments may be performed in some patients. In OA patents, the effect of intra-articular GC injections is less sustained than in those with joint inflammatory diseases and it persists for an average of about 3 weeks. Intra-articular hyaluronic acid is likely to be a more promising treatment for OA. It may also relieve pain considerably and improve joint functions. At the same time the highest effect was noted between weeks 5 and 13 after injection, but improvement also persisted after 14–26 weeks or longer in a number of cases.

The current treatment strategy for rheumatoid arthritis (RA) is based on the principles of early aggressive therapy and tight control, which are summarized in «Treat-to-Target» recommendations. The draft RA treatment guidelines by the Association of Rheumatologists of Russia (ARR) reflect these principles in expanded form. Twenty-four ARR recommendations contain the detailed description of current treatments for RA, which relies on the principles of evidence-based medicine. Some practical issues for the management of patients with RA require special attention. The comparison of a number of randomized trials and the author’s experience in the REMARCA study may conclude that subcutaneous methotrexate (MTX) in an initial dose 10–15 mg/week with its fast increase up to 20Р30 mg/week is an optimal first-line therapy for RA. To choose the period within which a decision should be made on the incorporation of biologic agents (BA) in patients with an inadequate response to MTX is a serious matter. The experience gained in a number of clinical trials, particularly in those of etanercept, shows that a 12-week follow-up is sufficient in most patients. First of all, it is important for early RA. After achieving sustained remission, the reasonable tactics is to accurately reduce the dose of a BA although there may also be complete therapy discontinuation («treatment holiday») in the future.