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ASAS health index (ASAS HI) is a comprehensive tool developed on the basis of the international system of ICF (the International Classification of Functioning, Disability and Health) to quantify the health of patients with spondyloarthritis (SPA), including ankylosing spondylitis (AS). ASAS HI is a questionnaire containing 17 questions, each related to a specific ICF pool (pain, emotions, sleep, sexual function, mobility, self-care and communication). ASAS HI additionally includes 9 questions (ASAS EF Item Set) to assess the impact of environmental factors on the health of the patient with SPA. The aim is a Russian translation and adaptation of the ASAS HI (including ASAS EF Item Set). Material and methods. Translation of ASAS HI and ASAS EF Item Set from English into Russian and its adaptation were carried out in five stages: the stage of direct translation; the stage of synthesis of translations and formation of the Russian version; the stage of reverse translation from Russian into English; the stage of comparison of the original English-language questionnaire with the result of reverse translation and the formation of the final Russian-language version; field test. Results and discussion. Three researchers performed an independent translation of ASAS HI (including ASAS EF Item Set), after which the fourth researcher created and agreed on a single Russian version of the questionnaire. Then two volunteers, for whom English is the main language, performed a reverse translation of ASAS HI from Russian into English (reverse translation). An independent researcher has compared the original and the resulting reverse translated English version of the ASAS HI, and then the three translators performed the joint correction of the text of the three questions, differing in English-language versions. The obtained second Russian-language version of ASAS HI (including ASAS EF Item Set) was tested by 10 patients with SPA: AS – 60%; non-radiological axial spondylitis (NR axSPA) – 40%, men – 60%; mean age – 32±12 years; duration of symptoms – 7.5±2.2 years; BASDAI index – 3.39±3.04; ASAS HI – 6,96±3,35.The average time to fill the questionnaire – 2,2±1,18 min. Patients rated the Russian version of the questionnaire as clear, easy to fill in and comprehensively characterizing health problems related to SPA. The results of testing Russian-speaking patients are comparable with the results obtained in testing 206 patients with SPA from 19 non-English-speaking and 4 English-speaking countries (AS – 65%; men – 59.7%; mean age – 42.4±13.9 years; duration of symptoms – 11.2±11.0 years; BASDAI – 3.8±2.3; ASAS HI – 7.1±4.4; filling time – 2.6±1.6 min). Conclusion. During the study translation and adaptation of the Russian version of ASAS HI, which is a tool for comprehensive assessment of health and function of patients with SPA, including AS were performed.

Etanercept (ETC), a soluble tumor necrosis factor-α (TNF-α) receptor, was registered for the treatment of spondyloarthritis in the Russian Federation in 2009. By now, results of prolonged treatment with this drug have been obtained in patients with ankylosing spondylitis (AS). Objective: to evaluate the efficiency and tolerability of long-term therapy with ETC in patients with AS. Subjects and methods. The follow-up included 60 patients with a documented diagnosis of AS (the 1984 New York criteria) and/or axial spondyloarthritis (the 2009 ASAS criteria), high activity (BASDAI >4), who received long-term (at least a year) regular therapy with subcutaneous ETC 50 mg weekly. Its effect was evaluated using the ASAS criteria. Results and discussion. ETC was the first TNF-α inhibitor used in 29 (48%) patients, including 22 (76%) patients who achieved partial remission; 7 (24%) patients who showed ASAS40 improvement. One patient was observed to have hepatotoxicity (alanine aminotransferase elevation to 72 U/l), therefore the drug was discontinued. 31 (52%) patients were switched to ETC after infliximab (n=24) or adalimumab (n=7) due to their poor tolerance and/or loss of effect. At the same time, ETC became the second anti-TNF-α drug in 21 (35%) patients and the third one in 10 (17%). During the therapy, 21 (68%) patients switched to ETC were noted to have ASAS40 improvement; 9 (29%) patients had partial remission. The insufficient effect of the drug was observed only in one patient (3%), in whom ETC was the third TNF-α inhibitor. The tolerability of ETC was generally satisfactory after switching from anti-TNF-α monoclonal antibodies (mAbs). Three patients developed de novo psoriasis that required therapy discontinuation in one patient; another male patient developed uveitis for the first time. In one female patient with AS associated with Crohn’s disease with loss of mAb effect, ETC became the third anti-TNF-α drug, during therapy with which there was no exacerbation of Crohn’s disease. The drug was well tolerated and highly effective in 8 patients, in whom ETC treatment was initiated at the age of 60 years and older: 6 (75%) achieved partial remission, 2 (25%) had ASAS40 improvement. Nine patients with previous and/or latent tuberculosis had no exacerbation of this disease during ETC therapy. Conclusion. During regular therapy with ETC, more than half of patients (52%) achieved partial remission according to the ASAS criteria, while this was more frequently achieved when the drug was used for the first time (76%) than when mAbs were switched to ETC (29%). Discontinuation of the latter due to adverse events was required only in 2 (3%) patients.

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

The paper gives the definition of remission in axial spondyloarthritides (axSpA), which has been developed by the Spondyloarthritis Study Group of Experts. The work used the Delphi technique. At stage 1, based on the analysis of the data available in the literature and on their own clinical experiences, the experts proposed some variants of the definition of remission and ways of its evaluation in patients with axSpA. At Stage 2, the definitions that had received at least 80% of the votes via anonymous voting were selected and adopted without further discussion. Those that had received an equal number of votes were reconsidered and additionally discussed; then there was repeat voting, by choosing the final definition. As a result of their discussion, the experts formulated the definitions of clinical laboratory and magnetic resonance imaging (MRI) remissions. They proposed the following remissions in axSpA: drug and drug-free, clinical laboratory, and MRI remissions, as well as a remission in the presence and absence of structural changes in the locomotor system, as evidenced by imaging techniques. Criteria for clinical laboratory remission and basic tools for its evaluation that can be used in real clinical practice and researches have been elaborated.

The paper gives recommendations for the drug therapy of axial spondyloarthritides, which have been developed by the Spondyloarthritis Study Group of Experts. The recommendations describe the patient management tactic in the most common clinical situations, which is aimed at maximizing the efficacy and safety of treatment.

Involvement of the aorta and heart valves in ankylosing spondylitis (AS) is a manifestation of the systemic inflammatory process. Data on the frequency, clinical significance, and evolution of these manifestations are controversial. Objective : to estimate the time course of echocardiographic (EchoCG) changes in the aorta and heart valves from the results of a prospective follow-up study of patients with AS. Subjects and methods. In 2008 to 2015, the V.A. Nasonova Research Institute of Rheumatology followed up 45 patients (35 men and 10 women) with documented AS that was consistent with the modified New York criteria and the original EchoCG changes in the aorta and heart valves. All the patients underwent transthoracic echocardiography at baseline and after 1–5 years. At baseline, there was aortic root dilatation (>37 mm) in 15 patients, thickening of the aortic walls and aortic valve (AV) cusps in 21 and 32 patients, respectively, as well as thickening of the mitral valve (MV) cusps in 15, and valve prostheses in 5 patients (2 had AV and MV prostheses). Aortic regurgitation (AR) was recorded in 19 patients (grades 1–2 AR in 15 patients and grades 3–4 in 4 patients); grades 1–2 mitral regurgitation (MR) was seen in 20 patients. Ten patients had subaortic pectinate thickening (SPT) in the aortomitral junction area. Of the 45 patients, 16 took biological agents (BA); 29 received traditional therapy, including 14 patients who used nonsteroidal anti-inflammatory drugs, 11 and 4 patients had sulfasalazine and methotrexate, respectively. Results and discussion. Repeated examinations revealed negative changes in 27 (60%) of the 45 patients. Progressive aortic dilatation (1 to 6 mm) was found in 12 (80%) of the 15 patients; dilatation appeared during follow-up in 2 patients. Fourteen patients were noted to have negative valve changes: the emergence of cusp thickening in the valves (that in AV and MV in 9 and 4 patients, respectively; both in 1 patient). Four patients underwent valve replacement: 3 and 1 patients underwent AV and MV replacements, respectively. Ten of the 19 patients were observed to have AR progression by 2 grades in 2 (10.5%) patients and by one grade in 8 (42.0%) patients. MR progression by one grade was noted in 6 (30.0%) of the 20 people. A negative correlation was found between BA therapy and aortic dilation progression (r = -0.329; p = 0.03). SPT appeared in 3 patients. Of the 10 patients who had a baseline SPT, its reduction (8 to 3.5 mm) was seen in one patient; complete regression was identified in two patients; all received BAs. Thus, pathological changes in the aorta and heart valves in AS are progressive in most patients. SPT may regress, which reflects apparently a reduction in the severity of active inflammation of the aortic root. Active anti-inflammatory treatment may play a protective role in the progression of aortic dilatation.

The paper gives the recommendations for the assessment of disease activity and functional status in patients with ankylosing spondylitis in clinical practice, which have been developed by experts, by taking into account international and Russian experience in managing these patients.

Ankylosing spondylitis (AS) is a systemic inflammatory disease involving not only the skeleton, but also other organs. The data on the frequency and clinical significance of extraskeletal manifestations are contradictory. Objective: to assess the frequency and severity of extraskeletal manifestations (ESMs) of AS in the authors' own clinical practice. Subjects and methods. 452 patients (363 men and 89 women) with AS fulfilling the 1984 relevant New York criteria were examined at the V.A. Nasonova Research Institute of Rheumatology in 2005 and 2014. The patients' median age was 31.5 [24; 41] years; median disease onset age, 19 [15; 23] years; disease duration, 11 [7; 18] years; HLA B27 was identified in 442 (97.7%) patients. In addition to standard laboratory and instrumental examinations, transthoracic echocardiography was performed in 172 patients. Rehberg's test, IgA test, histological examination of subcutaneous fat tissue or duodenal mucosa for amyloid, and renal ultrasound were made if there were urinary abnormalities and elevated creatinine levels. If indicated, there were consultations by an ophthalmologist with an appropriate instrumental examination (with evidence of uveitis in the history), a dermatologist, a nephrologist, an urologist, a gastroenterologist, and a endoscopist. Uveitis, cardiac involvement (conduction disturbance, aortic and valvular changes), inflammatory bowel disease (IBD), glomerulonephritis, and psoriasis were borne in mind as ESMs. The absolute number and percentage of patients having any ESM over the follow-up period were estimated. The number of exacerbations per year and that of complications were taken into account when evaluating uveitis; the magnitude of valvular regurgitation and the presence of prosthetic valves and a pacemaker were considered when assessing cardiac damage; the total body surface area (BSA) and the psoriasis areas and severity index (PASI) were estimated in psoriasis; the presence and stage of chronic kidney disease (CKD) and/or macrohematuria were kept in mind in nephropathy; when evaluating IBD, the Harvey–Bradshaw index (HBI) was determined on the basis of a stool frequency, the presence of blood in the stool, abdominal pain, and general well-being. Results and discussion. ESMs were detected in 218 (48%) of the 452 patients. Uveitis was present in 140 (30%) patients; in one-fourth of them, it relapsed frequently: three or more exacerbations per year and more than 10 during the disease; 41 (29%) patients had uveitis complications accompanied by visual impairment. Cardiac conduction disturbance was revealed in 61 (13%) patients. Five of them underwent pacemaker implantation. 71 (41.2%) patients were found to have aortic and valvular changes, including aortic root dilatation/thickening in 60 (34.8%) patients and aortic/mitral valve leaflet thickening in 63 (36.6%). Grades 3 and 4 valvular regurgitation was noted in 10 (5.8%) patients; valve replacement was carried out in 9 (5.2%) cases. Nephritis was diagnosed in 16 (3.5%) patients, 4 of them had Stage 2 or above of CKD. Psoriasis was present in 17 (3.7%) patients; 2 of them had severe psoriasis (BSA >10%). IBD (ulcerative colitis or Crohn's disease) was diagnosed in 16 (3.5%) patients, including 4 who showed a severe course. 79 (36%) patients were observed to have a concurrence of two or more ESMs; that of uveitis and heart disease was most commonly seen. Conclusion. ESMs are observed in nearly half (48%) of the patients with AS and can be concurrent; the most common ESMs of AS are uveitis, aortic root and heart valve lesions, and cardiac conduction disturbance. ESMs worsen the course and prognosis of AS.

Relapsing uveitis is a serious problem for patients with ankylosing spondylitis (AS). Tumor necrosis factor- α inhibitors significantly reduce the frequency of uveitis attacks in AS patients, but they are not always available. In this connection, it is appropriate to evaluate the effect of traditional disease-modifying antirheumatic drugs on the course of uveitis in AS. Objective: to compare the frequency of uveitis attacks in AS during combined therapy using sulfasalazine (SULF) and nonsteroidal anti-inflammatory drugs (NSAIDs) versus monotherapy with NSAIDs. Subjects and methods. A total of 111 patients with significant AS who had at least one uveitis attack during the disease were examined. 49 subjects received combined therapy including SULF 2 grams daily and NSAIDs for at least 1 year. Six of the 49 patients were noted to have frequently relapsing uveitis (above 3 episodes yearly); 43 had no more than 3 ones per year. The remaining 62 patients took NSAIDs only throughout the follow-up period. Nine of them had an average of 3 uveitis attacks per year; 53 had no more than 3 ones per year. Out of the 49 patients receiving combined therapy with NSAIDs and SULF, 23 took NSAIDs only at least 1 year before SULF use; 10 of them were observed to have frequent relapses in that period and 13 had three or fewer episodes. Results and discussion. The entire group showed an average of 2.06±2.04 uveitis attacks per year during monotherapy with NSAIDs and 1.41±1.83 attacks yearly during combined therapy with NSAIDs and SULF (p = 0.08). Among the patients with less than 3 uveitis attacks per year, the mean number of episodes was significantly fewer during combined therapy than during NSAID monotherapy: 0.99±0.87 and 1.37±0.91, respectively (p = 0.04). Among those with frequently relapsing uveitis (more than 3 attacks per year), the mean number of episodes yearly was not significantly different during NSAID monotherapy and combined therapy: 5.7±2.5 and 5.5±2.7, respectively (p = 0.9). In a subgroup of patients receiving sequentially NSAID monotherapy and combined therapy with NSADs and SULF, 13 patients with three or fewer baseline attacks per year displayed a significant reduction in the frequency of episodes from 1.92±0.96 to 0.4±0.44 (p = 0.00003). During combined therapy versus monotherapy, 10 patients with frequently relapsing uveitis (over 3 episodes yearly) exhibited an insignificant reduction in the number of relapses from 5.9±3.02 to 5.33±1.1 (p = 0.6). Conclusion. Combined therapy with SULF and NSAIDs does not substantially affect the frequency of uveitis episodes in AS patients with frequently relapsing uveitis (above 3 attacks per year), but significantly reduces the number of episodes among patients with its mild course (less than 3 attacks yearly).

The paper gives the draft guidelines elaborated by the Expert Spondyloarthritis Diagnosis and Treatment Group by order of the Association of Rheumatologists of Russia. The guidelines include the essentials of how to use nonsteroidal anti-inflammatory drugs in axial spondyloarthrititides, including ankylosing spondylitis, contain instructions for how long they should be administered, and describe possible patient management tactics in the most common clinical situations and a preferential algorithm for evaluating the efficiency and safety of treatment.

The paper provides guidelines for the use of tumor necrosis factor- α (TNF- α ) inhibitors in the treatment of patients with axial spondyloarthritis (axSpA), including ankylosing spondylitis. It gives data on the efficacy of TNF- α inhibitors in patients with non-radiographic axSpA. By using international and Russian guidelines, the authors lay down indications for this therapy and criteria for evaluation of its efficiency and safety.

At present, there are a number of unsolved problems associated with unawareness of the causes and ways to prevent the inefficacy of tumor necrosis factor-α inhibitors. Objective: to study the causes of secondary inefficacy of infliximab (INF), by analyzing its concentrations and antidrug antibody levels in the serum of ankylosing spondylitis (AS) patients receiving long INF, as well as a possibility to overcome its secondary inefficacy through plasmapheresis. Subjects and methods. 54 patients with active AS (BASDAI > 4) underwent regular long-term (1-to-10-year) treatment with INF 5 mg/kg according to the standard scheme. During the therapy blood samples were taken before a regular INF infusion to quantify the levels of antibodies to the drug and its concentration. According to the efficiency of the drug, two groups were formed: 1) 27 (50%) patients with INF inefficacy (an exacerbation occurred 2–4 weeks after infusion); 2) 27 patients with drug efficacy. The levels of anti-double stranded DNA antibodies and antinuclear factor were estimated in 27 patients to investigate a relationship between the immunogenicity of INF and the presence of autoantibodies in its secondary inefficacy. A plasmapheresis session was carried out in 5 patients before a regular IFN infusion. Results and discussion. Anti-INF antibodies were found in 28 (52%) patients, these being more common in the patients with drug inefficacy than in the others (67 and 37%, respectively; p < 0.05). In the patients with INF inefficacy, anti-INF antibody levels were significantly higher than in those with preserved drug effect (18.33 and 4.67 U/ml, respectively; р < 0.05). Moreover, the serum concentration of INF was not significantly different in these groups (1.6 and 2.96 μg/ml). There was an inverse correlation between INF concentrations and anti-INF antibodies (r = -0.7; p < 0.05). The level of autoantibodies did not correlate with that of anti-INF antibodies. Following plasmapheresis, the level of anti-INF antibodies dropped in all the patients and the concentration of the drug increased in only three of the five patients; in two of them anti-INF antibody levels were initially low (p < 0.05). Plasmapheresis promoted a short-term restoration of INF efficacy no matter what the baseline level of anti-INF antibodies. Conclusion. The secondary inefficacy of INF may be associated with not only the emergence of its neutralizing antibodies and the reduction in serum drug concentration, but also with other yet unknown causes. There is a need for further investigation of the causes of secondary INF insufficiency and methods for its overcoming.

By the end of the first decade of the 21st century, spondyloarthritis studies have accumulated a certain number of terms that are obsolete, but used by physicians in their everyday speech, on the one hand, and a great variety of different definitions, on the other hand. In January 2014, the first organizational meeting of the Expert Group on Spondyloarthritis, Association of Rheumatologists of Russia, decided that its primary task should be to order the terminology used in this area. The authors primarily collected the terms, which had been already used in medical vocabulary, and then divided them into two categories: obsolete definitions and terms to be finalized and unified. This publication gives guidelines for using the medical terms relevant to spondyloarthritis and separately discusses how to correctly write the term sacroiliitis.

Objective. The risk of AS is associated with genomic variants related to antigen presentation and specific cytokine signalling pathways, suggesting the involvement of cellular immunity in disease initiation/progression. The aim of the present study was to explore the repertoire of TCR sequences in healthy donors and AS patients to uncover AS-linked TCR variants. Methods. Using quantitative molecular-barcoded 50-RACE, we performed deep TCR beta repertoire profiling of peripheral blood (PB) and SF samples for 25 AS patients and 108 healthy donors. AS-linked TCR variants were identified using a new computational approach that relies on a probabilistic model of the VDJ rearrangement process. Results. Using the donor-agnostic probabilistic model, we reveal a TCR b motif characteristic for PB of AS patients, represented by eight highly homologous amino acid sequence variants. Some of these variants were previously reported in SF and PB of patients with ReA and in PB of AS patients. We demonstrate that identified AS-linked clones have a CD8(+) phenotype, present at relatively low frequencies in PB, and are significantly enriched in matched SF samples of AS patients. Conclusion. Our results suggest the involvement of a particular antigen-specific subset of CD8+ T cells in AS pathogenesis, confirming and expanding earlier findings. The high similarity of the clonotypes with the ones found in ReA implies common mechanisms for the initiation of the diseases.

Uveitis is a common extraskeletal manifestation of ankylosing spondylitis (AS) occurring in 20–40% of patients. Most authors underline a favorable prognosis for AS-associated uveitis. Objective: to study features of clinical picture and progression of AS-associated uveitis and to estimate the occurrence of its complications. Subjects and methods. Across-sectional study of 140 patients (98 males and 42 females) with AS, who had at least one uveitis attack over the period of disease and was followed up at V.A. Nasonova Research Institute of Rheumatology during 2008–2012. In addition to standard rheumatologic examination all patients were examined by ophthalmologist. Biomicroscopy, ophthalmoscopy, tonometry, computer-assisted perimetry, ultrasonography (B-scanning) of eyes and, if needed, fluorescein angiography and electrophysiological examination of retina were performed. Localization of uveitis, presence of complications affecting vision, total number of uveitis attacks by the moment of examination, mean number of uveitis attacks per year, correlation between the frequency of attacks and complications, presence of other extraskeletal manifestations and peripheral arthritis were assessed. The total number of uveitis attacks was defined from patients' interviews and respective medical documentation. Mean number of uveitis attacks was calculated as ratio of total number of uveitis attacks to the duration of disease for each patient. In the case of more than two attacks per year uveitis progression was considered refractory. Results. Mean duration of the disease was 17.7±11.03 years. In 19 patients (14%) AS manifested before and in 121 (86%) – after the age of 16 years. HLA-B27 was revealed in 135 (96%) patients, peripheral arthritis – in 43 (30%), whereas other extraskeletal manifestations – in 46 (32%). Early onset of uveitis in first 10 years of the disease was recorded in 81 (58%) patients, after10 years – in 21 (15%). Uveitis was the first clinical symptom of AS in 37 (26.4%) patients. 33 (24%) patients had more than 10 uveitis attacks during the disease, 17 (12%) – more than two attacks per year, whereas 18 (13%) had chronic uveitis. 118 (84%) had localized iridocyclitis, 12 (8%) – panuveitis, 2 (1%) – localized posterior uveitis. 122 (87%) patients had unilateral uveitis, 18 (13%) – bilateral, whereas 45 (36%) – alternating eye lesions (OD-OS). Uveitis complicated with vision impairment was observed in 41 (29%) patients: synechia in 26 (18%), vitreous degeneration – in 20 (14%), cataract – in 32 (23%), glaucoma – in 13 (9%), maculopathy – in 6 (4%), ribbon-like retinal degeneration – in 6 (4%), partial optic nerve atrophy – in 3 (2%). Authors revealed direct correlation between frequency of uveitis attacks and occurrence of synechia, cataract, glaucoma, vitreous degeneration. Conclusion. AS-associated uveitis is predominantly characterized by unilateral iridocyclitis (84%) and the onset in the first 10 years of disease (84.4%); 25% of cases were remarkable for frequent relapses: more than two attacks per year and more than 10 during the period of disease. One third of patients demonstrated vision impairments, and its progression correlated with the frequency of uveitis attacks.

The project of working classification of ankylosing spondylitis is described. New concepts for this disease [e.g., stages of disease (rather than stages of sacroiliitis), extra-axial and extraskeletal manifestations] are proposed and comprehensively interpreted. The main complications of the disease are described. Recommendations for diagnostic formulation are presented.

Parathyroid diseases cause serious musculoskeletal problems. The major function of parathyroid hormone (PTH) is to regulate calcium levels in the body, which is closely related to vitamin D. PTH exerts a double (anabolic and catabolic) effect on the human skeleton, which accounts for its heterogeneous action on the bone and for the major clinical manifestations of diseases associated with its hyper- and hypoproduction. The paper considers the main causes of hypoparathyroidism (HPT) that is considered to mean inadequate PHT activity and/or secretion; moreover, the level of ionized calcium falls below the reference range. It describes two HPT cases that show the clinical picture resembling ankylosing spondylitis.

Objective: to study the clinical picture of ankylosing spondylitis (AS), the association of its manifestations with the degree of disability in the real practice of a rheumatologist in Russia. Subjects and methods. The investigation enrolled 464 patients with AS, who had consecutively visited rheumatologists for 4 months in 24 cities and towns of the Russian Federation. A specially designed clinical card was filled out for all patients. Later on, the diagnosis of the disease was verified at the Research Institute of Rheumatology, Russian Academy of Medical Sciences, according to the 1984 modified New York criteria and pelvic survey X-ray films were assessed by two independent experts in a blind fashion. Results. The valid diagnosis of AS was confirmed in 330 (71.1%) out of all 464 patients included into the study; their mean age was 39.7±10.2 years; the mean duration of disease was 14.6±2.6 years; 86% were men and 14% were women. About half (47%) of the patients had peripheral arthritis and 56% had clinical signs of coxitis. The mean BASDAI and BASFI scores were 4.8±2.1 and 4.3±2.6, respectively. 61% of the patients had a BASDAI score of >4.0. Uveitis was the most common extravertebral manifestation (22%). One third of the patients did not work because of health reasons; 45% of the patients changed their work activities due to disease. Conclusion. In Russia, AS is characterized by its high activity, frequent involvement of hip joints and poor functional status in the patients on average 15 years after the onset of the disease. Loss of working capacity was observed in one-third of the patients. In the country, AS is diagnosed very late, on average 9 years after the disease onset.

Objective: to estimate the value of clinical parameters of uveitis for the diagnosis of spondyloarthritis (SA). Subjects and methods. One hundred and five uveitis patients referred by ophthalmologists to the Research Institute of Rheumatology, Russian Academy of Medical Sciences, in 2007–2009 were examined. X-ray study of the pelvis and lumbar spine, HLA-B27 test, and objective examination were performed in all the patients to detect inflammatory back pain, arthritis, and enthesitis. Results. The diagnosis of SA was verified in 60 patients: 24 had ankylosing spondylitis, 2 had reactive arthritis, and 38 had undifferentiat ed SA. The diagnosis of SA was discarded in 45 patients. Subsequent examination of these patients diagnosed BehНet's disease in 2 of them, sarcoidosis in 1, toxoplasmosis in 4, virus infection-associated uveitis in 8, Fuchs' syndrome in 1, and unspecified uveitis in 29. There was unilateral uveitis in 51 (85%) of the 60 patients with SP and in 26 (58%) of the 45 patients without SP (p = 0.0033); alternat ing eye lesion in 30 (50%) of the 60 patients with SP and in 4 (8.9%) of the 45 patients without SP (p = 0.00001); anterior uveitis in 57 (95%) of the 60 patients with SP and in 32 of the 45 patients without SP (p = 0.0017); posterior uveitis in 6 (10%) of the 60 patients with SP and in 20 (44%) of the 45 patients without SP (p = 0.0001); panuveitis in 2 (3.3%) of the 60 patients with SP and in 10 (22.2%) of the 45 patients without SP (p = 0.0039), acute recurrent uveitis in 15 (33.3%) of the 45 patients without SP and in 44 (73%) of the 60 patients with SP (p = 0.0001). The age at onset was less than 30 years in 38 patients with SP and in 19 patients without SP (p = 0.04). Conclusion. The estimation of the location and course of uveitis is important in diagnosing SP that is probable in patients with acute anteri or unilateral uveitis with alternating eye lesion, which occurred before the age of 30 years.

Small bowel (SB) injury is a common complication from the use of nonsteroidal anti-inflammatory drugs (NSAIDs). According to clinical trials, selective cyclooxygenase-2 inhibitors are safer in this respect. Meloxicam belongs to selective NSAIDs; however, its effect on the SB has been inadequately investigated. Objective: to compare the effects of meloxicam 15 mg/day and diclofenac 150 mg/day on the SB mucosa. Subjects and methods. A study group comprised 15 patients, including 6 men and 9 women (mean age 42.3+17.1 years), with ankylosing spondylarthritis (AS); 7 of them took meloxicam 15 mg/day for at least one month and 8 had diclofenac 100-150 mg/day. The SB was evaluated from capsule endocopy (CE) readings. Results. SB erosions (n = 3 to 20 or more) were found in 11 patients: 5 (71.3%) and 6 (75.0%) subjects taking meloxicam and diclofenac, respectively (p = 0.82). The average amount of erosions in those receiving meloxicam (6.2+4.7) was less than in those having diclofenac (9.4+7.3; p = 0.13). One patient taking diclofenac was suspected of having Crohn's disease shown by CE and then confirmed by colonoscopy. Conclusion. Meloxicam has demonstrated a less negative effect than diclofenac on SB, although this difference was statistically insignificant. Small and bowel pathology frequently occurs in patients with AS and may be associated not only with the negative effect of the drugs, but also with comorbid inflammatory bowel diseases. There is a need for further studies of the distal gastrointestinal tract and for those of the effect of NSAIDs on the SB.

The duration of continuous use of infliximab is more than 8 years in patients with ankylosing spondylitis (AS). The efficiency of the drug persists in most patients during its long-term regular therapy. Objective. To evaluate the effectiveness and safety of long-term infliximab therapy in patients with AS, particularly in those with a treatment interruption of ≥16 weeks, and to analyze the effect of the drug on various clinical manifestations of AS. Subjects and methods. The follow-up included 62 patients with a valid diagnosis of AS (New York criteria 1984) who received long-term (≥1 year) regular infliximab therapy in the Anticytokine Therapy Room, Research Institute of Rheumatology, Russian Academy of Medical Sciences. The dose of infliximab was 5 mg/kg. The following parameters: BASDAI and BASFI indices, global AS activity, the number of inflamed joints, enthesitis, and erythrocyte sedimentation rate were estimated in all the patients before therapy and each infusion. Improvement was determined by the ASAS criteria. Effectiveness was ascertained based on the maximum ASAS improvement that was observed per at least 75% of visits. Account was taken of the following clinical manifestations of AS: spondylitis, peripheral arthritis, coxitis, dactylitis, heel enthesitis, psoriasis, and inflammatory bowel diseases. A subgroup of 17 patients who had a forced increase in infliximab infusion intervals from 16 weeks to 3 years was separately identified in the study group. Results. The mean age of all the patients was 32.7 years; the mean duration of AS was 13.4 years; the mean therapy duration was 2.5 years. The therapy was performed for more than 3 and more than 5 years in 13 and 22 patients, respectively. According to therapy response, all the patients were divided into 3 groups: 1) those with ASAS improvement; 2) those with partial remission; 3) those with secondary inefficiency. Partial remission was observed in 35 (57%) patients; ASAS 40 improvement was seen in 15 (24%); secondary inefficiency developed in 12 (19%) patients. Peripheral arthritis was significantly less common in the group of patients who had achieved partial remission versus those who had achieved 40% improvement and those who had developed secondary inefficiency (p < 0.05, Fisher's exact test). The reasons for a time break in therapy with infliximab were the absence of the drug (n = 11), Mantoux test conversion (n = 2), pregnancy (n = 2), adverse events (n = 2). The mean therapy break was 20.7 (range 16-144) weeks. After therapy resumption, persistent efficacy of infliximab remained in all the patients. During the first infusion after interruption, all the patients were given premedication with the H1- histamine receptor blocker cetirizine in a dose of 10 mg/day and 10 patients received additionally glucocorticoid (GC) premedication. Infusion reactions were observed in 4 (24%) patients during the second (after interruption) infusion without GC premedication. Infliximab was discontinued because of infusion reactions in 2 (12%) of these patients. Conclusion. The majority of patients with AS could achieve persistent partial remission during long-term infliximab therapy. Secondary infliximab inefficacy occurred more commonly in patients with peripheral arthritis. When the treatment was forcedly interrupted, the efficacy of infliximab after therapy resumption was not decreased and its tolerability became slightly worse - infusion reactions were seen in 24% of the patients; 12% required infliximab to be discontinued because of infusion reactions. When therapy is resumed after its > 16- week interruption, it is expedient to use cetirizine for 5 days and/or premedication with GC (prednisolone in a dose of 50 mg or dexaven in a dose of 8 mg).

Objective: To gain experience with adalimumab therapy in patients with ankylosing spondylitis (AS) and to clarify the effect of the drug on MRI-detectable inflammatory changes (IC) in the vertebral column and heel enthesis with the short-term use of this gene engineering biological. Subjects and methods. This open-label observation included 14 patients diagnosed as having AS in accordance with the modified New York criteria [4] and 3 patients with early undifferentiated spondyloarthritis (uSA). The ESSG criteria were used for the diagnosis of uSA. In addition to the BASDAI index, the new international index for disease activity in AS (ASDAS) proposed by the ASAS group in 2009 was first employed to assess the activity of AS. MRI-detectable IC in the thoracic spine, sacroiliac articulation, AND heel bones (in patients with heel enthesitis) was an additional criterion for AS activity. The results of adalimumab use were assessed at weeks 4 and 14 of the study. The efficiency of therapy was evaluated by the ASAS criteria, 40% improvement was taken into account, 50% improvement and partial remission were separately assessed; 50% improvement was assessed by the BASDAI index. The number of patients who had achieved partial remission after 6 adalimumab injections is the major efficiency criterion. Results. The median (Ме) age of all the patients was 31.6 years [range 22-56]; the Ме disease duration was 72 months [range 11-264]. HLA-B27 was detected in 83% of the patients. Peripheral arthritis and enthesitis were present in 12 and 9 patients, respectively. Partial remission was recorded in 17.8 and 41% of patients after 2- and 12-week adalimumab therapy, respectively; 40% ASAS improvement was observed in 58.8 and 76.6% of patients after 2- or more and 6-week therapy, respectively. The BASDAI activity index was decreased by 50% or more in 47 and 86.6% of the patients with the baseline high index after 2 and 6 injections, respectively. The ASDAS activity corresponded to low activity in 67 and 75% of the patients having the baseline high activity in this index (>3.0) after 2- and 12-week therapy, respectively. In 3 patients, 100% clinical improvement in heel enthuses was achieved, as confirmed by MRI data. Although the Ме IC in the thoracic spine substantially diminished from 8 (9) to 0 (1) following 12-week therapy, the differences were insignificant (p=0.07). After 12-week therapy, thoracic IC completely disappeared in one patient. Conclusion. Adalimumab therapy-induced improvement was frequently seen after just the first two injections of adalimumab and preserved after 12-week therapy. Adalimumab rapidly and considerably reduces the magnitude of inflammation in the spinal structures and entheses, as evidenced by МЫ data.

Анкилозирующий спондилит (АС) поражает молодых людей в наиболее продуктивном возрасте (на 3-ей декаде жизни) и с первых лет болезни оказывает негативное влияние на работоспособность, получение образования, создание семьи. Длительное время существовало ошибочное мнение, что эффективной терапии АС не существует, а большинство пациентов АС имеют хороший прогноз для жизни, поэтому своевременному диагнозу не придавалось должного значения. Около 70% пациентов АС через 10-15 лет теряют трудоспособность и имеют значительное снижение качества жизни [1]. Летальность у больных АС выше в 1,5-4 раза, а выживаемость пациентов после 40 лет течения АС на 12% меньше по сравнению с общей популяцией [2]. Среди всех хронических ревматических заболеваний самый длительный период времени от появления первых симптомом до установления достоверного диагноза АС отмечается у пациентов АС и составляет около 7 лет [3]. Несмотря на то, что заболевание описано более 100 лет назад, диагноз в течение первых 7-10 лет болезни (до формирования классической рентгенологической картины в позвоночнике) вызывает затруднения не только у врачей общей практики, но и у ревматологов. Это является одной из причин того, что распространенность АС, наиболее изученного заболевания из группы спондилоартритов, значительно различается в отдельных странах и колеблется от 0,2% до 1,9% в разных популяциях [4]. По данным недавнего эпидемиологического исследования распространенность АС и спондилоартритов в России ниже, чем в большинстве европейских стран (менее 0,1%) [5], что доказывает, что большая часть пациентов АС, по-видимому, наблюдаются с другими диагнозами.

Objective. To analyze and compare clinical, radiological and ultrasonic signs of coxitis in pts with ankylosing spondylitis (AS). Material and methods. 35 pts with AS and clinical signs of coxitis were included. Median age was 26 years, AS duration 9 years, coxitis duration 5 years. 17 pts with AS without clinical signs of coxitis constituted control group. Pain on visual analog scale, hip joint mobility, radiological changes and ultrasonic signs of exudation were assessed. Results. Among the pts with AS prevailed those with the beginning of the disease before 20 years of age (77%). 71% of pts had bilateral coxitis. In 40% of pts coxitis signs during the first years were inconstant. Most frequent radiological signs of coxitis were narrowing of joint space (91,9%), femoral head or/and acetabulum cysts (77,4%), femoral head osteophytes (67,7%). Femoral head deformity (8,1%), partial bone anchylosis (6,5%), marginal bone erosions (3%) acetabulum protrusion (1,6%) were rare signs. Exudation was present in 84% of damaged hip joints. Bone destruction was significantly more frequent in pts with longer duration of AS and coxitis and was associated with more prominent functional disability and higher frequency of exudation. Hip joint exudation frequency and its volume did not influence pain intensity. Radiological changes were revealed in 12 hip joints of 7 pts of control group.

First autologous hematopoietic SCT for ankylosing spondylitis: a case report and clues to understanding the therapy

Increasing evidence points to a role for killer immunoglobulin-like receptors (KIRs) in the development of autoimmune diseases. In particular, a positive association of KIR3DS1 (activating receptor) and a negative association of KIR3DL1 (inhibitory receptor) alleles with ankylosing spondylitis (AS) have been reported by several groups. However, none of the studies analyzed these associations in the context of functionality of polymorphic KIR3DL1. To better understand how the KIR3DL1/3DS1 genes determine susceptibility to AS, we analyzed the frequencies of alleles and genotypes encoding functional (KIR3DL1*F) and non-functional (KIR3DL1*004) receptors. We genotyped 83 AS patients and 107 human leukocyte antigen (HLA)-B27-positive healthy controls from the Russian Caucasian population using a two-stage sequence-specific primer PCR, which distinguishes KIR3DS1, KIR3DL1*F and KIR3DL1*004 alleles. For the patients carrying two functional KIR3DL1 alleles, those alleles were additionally genotyped to identify KIR3DL1*005 and KIR3DL1*007 alleles, which are functional but are expressed at low levels. KIR3DL1 was negatively associated with AS at the expense of KIR3DL1*F but not of KIR3DL1*004. This finding indicates that the inhibitory KIR3DL1 receptor protects against the development of AS and is not simply a passive counterpart of the segregating KIR3DS1 allele encoding the activating receptor. However, analysis of genotype frequencies indicates that the presence of KIR3DS1 is a more important factor for AS susceptibility than the absence of KIR3DL1*F. The activation of either natural killer (NK) or T cells via the KIR3DS1 receptor can be one of the critical events in AS development, while the presence of the functional KIR3DL1 receptor has a protective effect. Nevertheless, even individuals with a genotype that carried two inhibitory KIR3DL1 alleles expressed at high levels could develop AS.

Earlier studies have shown that high doses of TNF-alpha increase apoptosis in human autoimmune T-cell clones. Based on these studies, a treatment approach was proposed to reduce or eliminate autoimmune T cells in patients with type 1 diabetes using drugs that temporarily elevate TNF levels. Here, we report the treatment of ankylosing spondylitis patient with a single high oral dose of Likopid (glucosaminyl-muramyl dipeptide), which aimed at increasing the levels of TNF-alpha in order to induce apoptosis of autoreactive T cells. The flow cytometric analysis of blood samples collected before and after treatment demonstrated massive elimination of CD8(+) T cells. However, the treatment did not result in any notable therapeutic effect, and real-time PCR analysis demonstrated that stably expanded T-cell clones that were earlier tracked in this patient were unaffected. This report suggests that the controversial approach to eliminate autoimmune T-cell clones through overstimulation is not effective in treating ankylosing spondylitis.

An assay to measure avidity index (AI) was developed to diagnose incident hepatitis C virus (HCV) infections. The assay demonstrated an AI value statistically significantly lower in primary HCV infections than in chronic infections. When the assay was applied to past resolved infections, the difference in AI values was not as significant as the difference between incident and chronic infections. Lower AI values obtained in past resolved infections may be directly related to lower levels of immunoglobulin G anti-HCV in past resolved infections than in either new infections or chronic infections.

Objective: to estimate the sensitivity and specificity of ASAS (Assessment of Spondyloarthritis International Society) criteria for peripheral spondyloarthritis (SpA) in patients with early psoriatic arthritis (ePsA). Subjects and methods. Examinations was made in 45 patients (17 men and 28 women) with ePsA meeting the CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria (mean age, 37 years; disease duration, 1 year) and in 20 patients (9 men and 11 women) with signs of peripheral SpA meeting the ESSG (European Spondyloarthropathy Study Group) criteria (mean age, 23 years; disease duration, 2.25 years; control group). The investigators estimated 78/76 tender/swollen joints and enthuses using MASES (Maastricht Ankylosing Spondylitis Enthesitis Score) and assessed the presence of inflammatory spinal pain according to the ASAS criteria, psoriasis, uveitis, inflammatory bowel diseases, genitourinary and/or enteric infections, and a family history of SpA. They also performed X-ray studies of the hand and distal portions of the foot and pelvis and graded sacroilitis using the Kellgren scores. HLA-B27, C-reactive protein, and erythrocyte sedimentation rate were determined. The sensitivity/specificity, likelihood ratios, and clinical value of criteria were calculated. Results. 41/4 and 31/14 patents with ePsA met/unmet Criteria Sets I and II. The sensitivity/specificity of Sets I and II was 91.1/10% and 68.8/95%, respectively. One patient with ePsA and two patients in the control group did not meet one of the sing sets. The total sensitivity/specificity was 97.8/10%. In the control group, the sensitivity/specificity of Sets I and II was 91.1/100% and 68.8/100%, respectively. For ePsA, the positive likelihood ratio proved to be high for Set II (13.78%) and low for Set I (1.01). Conclusion. ASAS Criteria Set I for peripheral SpA is of low value in identifying ePsA and Sign Set II shows a high value in diagnosing ePsA as it includes the major clinical manifestations of the disease. Both the ASAS for peripheral SpA and CASPAR criteria may be used for the classification of PsA.

Objective: to study clinical manifestations of axial spondyloarthritis (axSpA) fulfilling ASAS criteria and to evaluate Russian version of modified New York criteria for the diagnosis of AS in Russian patients. Subjects and methods . Authors examined 73 patients aged 18–45 years suffering from inflammatory back pain for a period from 3 months to 5 years. BASDAI and ASDAS-CRP were used to assess activity, whereas BASFI – to evaluate functional status. Examination included: assessment of HLA-B27 rate, X-ray of pelvis and lumbar spine, ultrasonography of hip joints and calcaneal regions, magnetic-resonance imaging (MRI) of sacroiliac joints, lumbar spine and hip joints (if clinical signs of injury are present), densitometry of lumbar spine (LII–IV) and femoral neck. Results . Mean age of patients was 28.3±6.4 years, mean duration of disease – 19.9±14.4 months. HLA-B27 was found in 94.5% of patients. Mean BASDAI value was 4.1±1.9; ASDAS – 2.7±1.3; BASFI – 2.6±2.1. Peripheral arthritis was observed in 65.8% of cases, coxitis – in 31.5%, calcaneal enthesitis – in 61.6%, dactylitis – in 19.2%, low bone mineral density – in 17.8%. MRI showed inflammatory changes of axial skeleton in 84.9% of patients, active sacroiliitis (SI) – in 72.6%. X-ray revealed definite SI in 49.3% of patients («classic» AS). According to MRI data, 30.1% of patients with active SI and without structural changes of sacroiliac joints had pre-radiological stage of AS (by Russian version of modified New York criteria). 74.0% of patients fulfilled both sets of ASAS criteria for axSpA, 5.5% – met only I criteria set, whereas 20.5% – only II criteria set. Three groups of patients were defined. The first included patients with radiologically proven SI, the second – with MRI-proven SI and the third – patients without SI. Significant difference between the groups was detected either by gender (number of males in groups I and II exceeded that in group III: p1–3=0.002, p2–=0.033) or by the rate of high activity according to ASDAS index (observed in groups I and II more frequently than in group III; p=0.02 in both cases) or by presence of inflammatory changes in spine in MRI scans (detected in 26% of patients of group III, not detected in patients of group II; p=0.05). Conclusion. Half of patients with axSpA symptoms longer than 20 months already have structural changes in sacroiliac joints, so they can be diagnosed as «classic» AS. 80% of patients who had axSpA for less than 5 years match the description of AS provided by Russian version of modified New York criteria; one third of them has pre-radiological stage of disease. Number of males with radiologically proven SI and MRI-proven SI was larger than that of patients without SI. SI is often accompanied with high activity according to ASDAS. MRI showed that, inflammatory processes in spine may precede active SI. No clinical differences were revealed between patients with radiogically proven AS and pre-radiological stage of AS described by Russian version of modified New York criteria.

The course of uveitis in patients with ankylosing spondylitis (AS) does not always correlate with inflammation in the axial skeleton and peripheral joints. Effect of tumor necrosis factor α (TNFα) inhibitors on uveitis has been insufficiently studied yet, unlike their effect on the peripheral joints and spine. Objective. To compare the frequency of uveitis attacks in patients with AS during treatment with TNFα inhibitors and the conventional anti-inflammatory therapy. Materials and Methods. The study included 48 patients with AS and recurrent uveitis treated with TNFα inhibitors: 25 – infliximab, 15 – adalimumab, 9 – etanercept; 7 patients received two or more drugs sequentially. Median [25th, 75th percentiles] of the treatment duration was 3 [3.5; 5] years. The duration of treatment since the first attack of uveitis until administration of TNFα inhibitors was 5 [5; 9.7] years. Eighteen patients received only nonsteroidal anti-inflammatory drugs (NSAIDs), 30 patients received NSAIDs and basic anti-inflammatory drugs (DMARDs), including sulfasalazine (n = 23), methotrexate (n = 4), and cyclosporine (n = 4). Results. The median number of uveitis exacerbations during the standard anti-inflammatory therapy was 1 [0.4; 3] per year; during treatment with TNFα inhibitors – 0 [0; 0.5] per year (p = 0.0007). In 19 of 48 patients (40%), no exacerbations of uveitis were registered during therapy with these drugs. The frequency of uveitis attacks in patients treated with infliximab decreased from 1 [0.2; 2.75] to 0.1 [0; 0.8] episodes per year (p = 0.002), adalimumab – from 1.75 [1; 4.5] to 0 [0; 0.07] (p = 0.04), etanercept – from 0.95 [0.5; 1.75] to 0 [0; 0.07] (p = 0.001). Conclusion. Administration of TNFα inhibitors significantly reduces the frequency of uveitis attacks in patients with AS.

The article focuses on the problem of secondary ineffectiveness of tumor necrosis factor α infliximab (INF) and describes an attempt of using plasmapheresis (PF) to eliminate this problem in a patient with ankylosing spondylitis who had received INF treatment at a dose of 5 mg/kg for a long time (over 4 years). After PF, the IFF therapy ensured a long-term clinical and laboratory improvement of patient's condition. One can assume that PF made it possible to overcome secondary ineffectiveness of INF and can be used in some patients in cases when INF cannot be replaced with another TNFα inhibitor.

Objective: to evaluate the time course of inflammatory changes (ICs) in the spinal column and sacroiliac articulations (SIA) from magnetic resonance imaging (MRI) data in patients with ankylosing spondylitis (AS) during treatment with tumor necrosis factor-α (TNF-а) inhibitors or nonsteroidal anti-inflammatory drugs (NSAIDs), which were first used. Subjects and methods. MRI of the most painful part of the spine and SIA was performed in 58 patients with AS at baseline and 12 weeks later. MRI T2 STIR and T1 (SIGNA EXCITE, General Electrics; 0.35 T, matrix 288x192) regimens were used. Bone marrow edema was regarded as active inflammation. Active ICs in the most painful part of the spine were assessed by the AS spinal MRI activity (ASspiMRI-a) score and those in SIA by the Leeds scoring system. MRI was interpreted independently by two specialists; one of them did not know about the number of a visit and performed therapy. The patients were divided into two groups: 1) those who first used TNF-а inhibitors and 2) those who were first given NSAIDs. Both groups were matched for demographic indicators. Results. In both groups, the mean pain level in the spinal part under study decreased significantly in both groups: from 5.7±1.7 to 2.3±1.8 in the TNF-а inhibitor group (p = 0.000006) and from 4.8±2.3 to 2.6±2.3 in the NSAID group (р = 0.00001). After 12 weeks of treatment, the patients receiving TNF-а inhibitors (n = 28) showed a considerable reduction in the MRI signs of spinal ICs from 4.8±2.3 to 1.6±1.6 (p = 0.00001); moreover, this trend was more pronounced in patients (n = 17) with more baseline IC foci (≥ 5) than in those (n = 11) with fewer baseline IC foci (< 5) (the mean а was 4.3±1.5 and 1.6±1.4, respectively; р = 0.0003). In the patients taking NSAIDs (n = 30), the decrease in the number of spinal MRI ICs (from 2.8±2.5 to 2.3±2.1) was insignificant (p = 0.17). After 12 weeks, regression of active sacroiliitis was noted in 28 patients from the TNF-а inhibitor group with lower Leeds scores from 2.1±2.0 to 0 (p = 0.01). At baseline, 28.5% of the patients had MRI signs of active sacroiliitis, which were not found in any case at 12 weeks. At this time, the reduction in active sacroiliitis was also observed in the NSAID group patients (n = 30), but it was insignificant; the Leeds scores decreased from 2.6±2.5 to 2.1±2.0 (р = 0.083). At baseline and 12 weeks, the MRI signs of active sacroiliitis were present in 73.3 and 60% of the patients, respectively. During treatment with TNF-а inhibitors, the mean reduction in MRI IC scores during the follow-up was more marked than that in the use of NSAIDs (p = 0.003 for the spinal column and p = 0.013 for SIA). Conclusion. Pain intensity in the examined spinal part was significantly reduced in both the use of both TNF-а inhibitors and NSAIDs. MRI ICs significantly decreased when treated with TNF-а inhibitors rather than NSAIDs. With the greater magnitude of baseline MRI ICs, their drop was more significant during treatment with TNF-α inhibitors.

Objective: to compare different methods for estimating ankylosing spondylitis (AS) activity in the real practice of a rheumatologist in the Russian Federation. Subjects and methods. The investigation enrolled 464 patients with AS, who had consecutively visited rheumatologists for 4 months in 24 cities and towns of Russia. A specially designed clinical card was filled out for all patients. BASDAI and ASDAS scores were estimated by a physician and erythrocyte sedimentation rate (ESD) and C-reactive protein (CRP) were measured in all the patients. Mini-BASDAI scores were determined in patients with axial AS. The diagnosis of the disease was verified at the Research Institute of Rheumatology, Russian Academy of Medical Sciences, according to the 1984 modified New York criteria, by including X-ray film estimation. All activity assessment methods were compared. Results. The valid diagnosis of AS was confirmed in 330 (71.1%) out of all 464 patients included into the study; axial AS was present in 178 of them; their mean age was 39.7+10.2 years; the mean duration of disease was 14.6+2.6 years; 86% were men and 14% were women. About 61 and 74% of the patients (n = 178) had high BASDAI and mini-BASDAI scores, respectively; 88% had high and very high ASDAI (ESR) scores; the mean ESR (Westergren method) was 33.8+29 mm/h and CRP (n = 249) was 30 mg/l. Conclusion. On assessing the activity of disease, rheumatologists are primarily oriented to total activity scores and blood acutephase indicators (ESR and CRP) in real clinical practice. Patients with high disease activity calculated from BASDAI and ASDAS scores proved to be more. In its turn, ASDAS more frequently reveals high AS activity than BASDAI.

Objective: to compare the efficiency and tolerability of combination disease-modifying therapy with methotrexate (MT), sulfasalazine (SS), and hydroxychloroquine (HC) with that of MT monotherapy in patients with rheumatoid arthritis (RA). Subjects and methods. Sixty patients with RA, who had received no disease-modifying anti-inflammatory drugs, were enrolled in a 24-month open-label study. The patients were randomized into two groups at a 1:1 ratio. Group 1 received combination therapy with MT (its starting dose was 7.5 mg weekly), SS (2.0 g/day), and HC (200 mg/day); Group 2 had MT therapy. If there was no remission, the dose of MT was gradually increased from 7.5 to 17.5 mg weekly. The basic efficiency rate was a 50% improvement according to the American College of Rheumatologists criteria (ACR 50), which persisted at 9 months of therapy to the end of the study in the absence of adverse reactions (AR) requiring the therapy in question to be discontinued. Results. At 24 months of therapy, the effect corresponding to ACR 50 was observed in 16 (59.3%) of the 27 patients in Group 1 and in 11 (40.7%) of the 27 patients in Group 2 (p = 0.174). This effect persisted at 9 to 24 months in 9 (33.3%) patients in Group 1 and in 2 (7.4%) in Group 2 (p = 0.039). These patients had no AR that required treatment correction. By the end of the study, remission (DAS < 1.6) was seen in 6 (22.2%) patients in Group 1 and in 2 (7.4%) in Group 2 (p = 0.259). The groups showed no significant differences in the progression of X-ray signs of joint destruction. The assessment using the Sharp method indicated that the median erosion scores increased by a point in Groups 1 and 2; the median joint-space narrowing score rose by 8 and 7 points and the median total score increased by 10 and 6.5 points, respectively. There was a functional improvement in both groups. The median HAQ dropped from 1.5 to 0.5 scores in Group 1 and from 2.0 to 0.75 scores in Group 2. The tolerability of combination therapy and MT therapy did not differ greatly. Only 4 (13.3%) patients in Group 1 and 7 (23.3%) were withdrawn from the study because of AR. Conclusions. Combination disease-modifying therapy with MT, SS, and HC is more effective than MT monotherapy. Tolerability was comparable for both treatments.

Objective: to study associations between the lesion of the heart and aorta and other clinical manifestations and the characteristics of ankylosing spondylitis (AS). Subjects and methods. Three hundred and forty-four patients under 60 years of age with a valid diagnosis of AS without concomitant heart disease, followed up at the Research Institute of Rheumatology, Russian Academy of Medical Sciences, in 2005-2008, were examined. Of them, 64 (18.6%) patients had at least one attack of uveitis during the disease; 280 had never uveitis. During the disease, peripheral arthritis occurred in 160 (46.5%) patients; 184 (53.5%) had axial AS. All the patients underwent ECG; 101 had EchoCG (27 with uveitis and 74 without uveitis, 63 with arthritis and 38 without arthritis). Results. Forty-four patients were found to have cardiac conduction disturbances (atrioventricular or left bundle-branch block); of them 14 (31.8%) and 30 (68%) had uveitis and peripheral arthritis, respectively. Out of the 300 individuals without conduction disturbances, 50 (16.7%) and 130 (43%) had the above conditions (p = 0.01 and 0.003, respectively). Cardiac structural changes (aortic thickening/dilatation, subaortic bump, aortic and/or mitral leaflet thickening) were revealed in 45 patients; among them 21 (46.7%) and 34 (75%) had uveitis and arthritis, respectively; of the 56 patients without EchoCG changes, 6 (10.7%) and 29 (51%) had the above conditions (p = 0.0001 and 0.02, respectively). On the other hand, conduction disturbances were noted in 15 (23.4%) of the 64 patients with uveitis and in 29 (10.3%) of the 280 patients without this condition; p = 0.006; in 30 (19%) of the 160 patients with peripheral arthritis and in 14 (7.6%) of the 180 patients without arthritis; p = 0.003. Aortic and valvular changes were detected in 16 (59.2%) of the 27 patients with uveitis and in 28 (37.8%) of 74 without this condition; p = 0.04; in 36 (57%) patients with arthritis and in 9 (23%) of the 38 without arthritis; p = 0.018. There were no significant differences in the parameters of inflammatory activity between the groups. Conclusion. In patients with AS, cardiac lesion was significantly more frequently in the presence of uveitis and peripheral arthritis; uveitis and peripheral arthritis were significantly more common in patients with AS-induced cardiac changes.

Синдром SAPHO, названный по первым буквам основных симптомов (Synovitis - синовит, Acne – акне, Pustulosis – пустулез, Hyperostosis – гиперостоз и Osteitis - остеит) – редкое хроническое воспалительное заболевание неизвестной этиологии, характеризующееся сочетанием своеобразных кожных (ладонно-подошвенный пустулез, акне конглобата или акне фульминанс, гнойный гидраденит) и костно-суставных изменений (остеит различных локализаций и синовит) [2] Впервые это название было предложено в 1987 г. A. Chamot и соавт. [цит по 3]. В отечественной литературе, насколько нам известно, о наблюдениях синдрома SAPHO у взрослых до сих не сообщалось, хотя в 2004 г. В.В. Бадокиным был опубликован обзор сведений об этом заболевании [1]. В этом статье мы приводим наблюдения двух больных синдромом SAPHO.

Objective. To study heart damage in pts with ankylosing spondylitis (AS) by ECG and echocardiography (EchoCG). Material and methods. 344 pts with definite AS not older than 60 years without comorbid cardiac diseases examined in the Institute of rheumatology during 2005-2008 were included. ECG with 12 leads was performed in all pts and transthoracic EchoCG – in 101 pts. Results. Rhythm and conductivity disturbances were revealed in 67 from 344 (19,5%) pts: atrioventricular (a/v) heart block was present in 20 (5,8%) pts (16 had 1, 2 – 2 and 3 – 3 stage of a/v heart block). 27 (7,8%) pts had intraventricular heart block. EchoCG signs of aortal valve changes were revealed in 45 from 101 (44,5%) pts: thickness or dilatation of aorta – in 36 (35,6%), aortal valve cusps thickness – in 32 (31,7%), mitral – in 15 (14,8%). Local thickness in the form of a comb beneath aortal valve on the back wall of aorta basis at the site of its junction with basis of mitral anterior cusp – “subaortic bump” was found in 10 (10%) pts. Frequency of a/v heart block among pts with changes of aorta and cardiac valves was significantly higher than in pts without such changes. On the other hand frequency of aorta and cardiac valves changes in pts with a/v heart block was significantly higher than in pts without a/v heart block (p=0,0027) what shows relationship between conductivity disturbances and aorta and cardiac valves damage in AS. Conclusion. Cardiac pathology in AS is characterized by frequent (44,5%) damage of aorta basis and aorta-mitral junction zone in combination with thickness of aortal and mitral valves and conductivity disturbances.

Objective. To develop the optimal mode of spine evaluation with magnetic resonance image (MRl) in pts with ankylosing spondylitis (AS) and to study relationship between MR! signs of spinal inflammatory lesions (IL), spondylitis duration and clinical features of AS activity. Material and methods. MRl was performed in 36 pts (22 male, 14 female) fulfilling the modified NY criteria of AS. Median age of pis was 26 years (range 19 - 55), Median AS duration - 8 years (range 1,8 - 24). 34 (97%) pts were HLA-B27 positive. 21 (64%) pts had high AS activity - median BASDAI 40 (range 10 - 77). 92% of pts had inflammatory spine pain (VAS>20 mm) and 61% of pts had night pain. Median inflammatory pain duration had been defined separately for every part of the spine assessed by MRl. Median duration of axial pain was 36 months (range: 1-240). MR-scanning (Magnetom Symphony, Siemens, 1.5 T) was performed inTl, T2 and T2-FS (fat signal suppression) modes. IL scoring was done only in 29 pts evaluated in both sagittal and axial planes. We used two scoring methods: 1) individual IL score of the each spine element (vertebral bodies, processes, arches, zygapophyseai, costovertebral and costotransverse joints, ligaments), and 2) separate IL scoring in the vertebral bodies and posterior spinal elements in order "yes/no”. Results. 50 MRl images of different parts of the spine (8 cervical, 30 thoracic and 12 lumbar) have been obtained in 36 pts. Spine IL were found in 35 pts. 26% of all IL were revealed in axial planes. 3 pts with short AS duration had IL only on axial slices (zygapophyseai lumbar joints, costotransverse joints, processes). IL were revealed more often in thoracic (average score: 7.1), than in lumbar (3.7) and cervical (2.1) spine. In most (26 from 29 pts, 90%) pts IL were found in painful parts of spine. There was no IL score difference between pts(n=12) with low (BASDAI 40; n=17) AS activity. Me and range were 4 (1.8-10.3) and 6 (4-16), respectively; p=0.35. There was also no difference in percent of images with IL between pts with short (Me: 4 months, range: 1-18; n= 10) and prolonged (Me: 54 months, range: 24-180; n=16) duration of spondylitis (100% and 94% of images, respectively). However, pts with early spondylitis had significantly more IL in posterior spinal structures than in vertebral bodies (92.3% and 23.1% images, respectively; p