[Ocular manifestations of rheumatic diseases]. / Glaznye proyavleniya revmaticheskikh zabolevanii.

Rheumatic diseases are a large group of conditions of various origins, predominantly systemic in nature, with persistent or transient joint syndrome and involvement of other organs and systems, including the eyes. Many rheumatic diseases are characterized by specific types of ocular inflammation, which manifests through its localization, symmetry, and clinical features.

Course of Uveitis in Patients with Ankylosing Spondylitis during the Interleukin17 Inhibitors Therapy.

Biological disease-modifying antirheumatic drugs (bDMARDs) can have different effects on various clinical manifestations of ankylosing spondylitis (AS). Data on the effects of interleukin 17 inhibitors (IL17-i) on uveitis in AS continue to accumulate. Objective: to evaluate the effect of IL17-i therapy on the course of uveitis in AS. The study involved 73 patients with AS (New York criteria, 1984), who received IL17-i (57-secukinumab (SEC), 22-netakimab (NTK)) for at least 1 year. The average age of patients at the time of inclusion in the study was 41.93 ± 8.95 years, the average duration of AS was 10.75 ± 6.22 years. There were 40 men (56.7%) and 33 women (43.3%) among the patients. HLA-B27 was detected in 62/73 (85%), coxitis in 58 (79%), enthesitis in 63 (86.3%), peripheral arthritis in 57 (78%), psoriasis in 7 (9.5%), and inflammatory bowel disease (IBD) in 3 (4.1%) patients; in 6 (8.2%) patients, the disease started before the age of 16; 19 (26%) patients had at least one episode of uveitis during the course of the disease. The rates of uveitis was estimated by comparing the number of incidences per 100 patient-years before the start of bDMARDs therapy and during IL17-i using. The incidence rate of uveitis before the start of bDMARDs therapy for all patients was 8.3 per 100 pt-years (95% CI 0.065-0.107), during IL17-i therapy- 9.2 per 100 pt-years (95% CI 0.06-0.15), p = 0.72. The incidence rate of uveitis among patients who used SEC was 10.1 per 100 pt-years (95% CI 0.079-0.13) before the start of bDMARDs therapy and 9.4 per 100 pt-years (95% CI 0.05-0.15), p = 0.74 during SEC therapy. The incidence rate of uveitis among patients who used NTK was 4.8 per 100 pt-years (95% CI 0.028-0.08) before the start of bDMARDs therapy and 7.1 per 100 pt-years (95% CI 0.019-022), p = 0.3 during the NTK therapy. For patients with a history of uveitis, the incidence rate of uveitis was 22.5 per 100 pt-years (95% CI 0.18-0.28) before the start of therapy with bDMARDs and 29.1 per 100 pt-years (95% CI 0.18-0.43), p = 0.29 during IL17-i therapy. Occurrences of uveitis were observed in 4 of 57 patients (7%) during SEC therapy and in 1 of 25 (4%) patients during the NTK therapy. One case of new-onset uveitis was recorded during the using of SEC. There were no significant differences in the incidence rates of uveitis during IL17-i therapy compared with non-biological therapy. IL17-i therapy have not demonstrated a significant effect on the course of uveitis in AS in the study group.

[New possibilities in therapy of ocular inflammation in rheumatic diseases]. / Novye vozmozhnosti terapii vospaleniya glaz pri revmaticheskikh zabolevaniyakh.

This review is devoted to the potential application of genetically engineered biological drugs of different classes in the treatment of main forms of uveitis and other types of non-infectious ocular inflammation in immunoinflammatory rheumatic diseases. The article presents the results of studies demonstrating the influence of interleukin-17 inhibitor secukinumab on the course of uveitis in spondylarthritis, shows the possibilities of treating uveitis in juvenile idiopathic arthritis with inhibitors of interleukin-6, co-stimulation of T-lymphocytes. Inhibition of interleukin-1 is considered an effective method of influencing the ocular inflammation in monogenic autoinflammatory syndromes and Behcet's disease. Rituximab is considered as an option for immunosuppressive therapy of non-infectious uveitis and scleritis.

[Genetically engineered biological agents in the treatment of uveitis in patients with ankylosing spondylitis (clinical observations)]. / Genno-inzhenernye biologicheskie preparaty v lechenii uveita pri ankiloziruyushchem spondilite (klinicheskie nablyudeniya).

The article describes clinical cases with effective use of some genetically engineered biological agents for arresting and preventing uveitis attacks, and discusses the potential usage of tumor necrosis factor (TNF)-alpha inhibitors and interleukin-17 inhibitors in the treatment of uveitis in patients with ankylosing spondylitis.

[Behçet's disease and uveitis]. / Bolezn' Bekhcheta i uveit.

This literature review is dedicated to the Behçet's disease - a multi-symptom, severe autoimmune condition, relatively rare among the population of the former Soviet republics, and to one of its three most frequent manifestations - uveitis.

[Nonsteroidal anti-inflammatory drugs in the treatment of anterior uveitis associated with spondyloarthritis]. / Nesteroidnye protivovospalitel'nye preparaty v lechenii perednego uveita pri spondiloartritakh.

Anterior uveitis (AU) is one of the common extraskeletal manifestations of spondyloarthritis (SpA). The course of AU in patients with SpA is characterized by frequent relapses. The article considers the question of local and systemic use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment and prevention of SpA-associated uveitis exacerbations.

[Features of the course of anterior uveitis associated with HLA-B27 antigen]. / Osobennosti techeniia perednikh uveitov, assotsiirovannykh c HLA-B27-antigenom.

PURPOSE: To perform comparative analysis of the frequency of various complications of anterior uveitis associated with HLA-B27 antigen in patients with and without spondyloarthritis. MATERIAL AND METHODS: Retrospective analysis included 189 patients with anterior uveitis (AU) associated with histocompatibility antigen (HLA-B27). The Follow-up period lasted 10 years. RESULTS: 189 patients with AU associated with antigen HLA-B27 were divided into two groups. The first group included 108 patients with various diseases of the spondyloarthritis (SpA) group; the second study group consisted of 81 patient with no signs of SpA. Number of patients with complications was 1.5 times higher in the first group. Complicated cataract, glaucoma, synechiae, myodesopsia occurred significantly more frequently in patients of the first group compared to AU patients of the second group, where idiopathic AU was more prevalent. Cystoid macular edema, corneal degeneration, optic nerve atrophy were observed more often in patients with SpA, but differences between the groups were statistically insignificant. Combination of complications also occurred significantly more often in SpA patients. Comparison of the frequency of AU attacks showed that the amount of uveitis attacks per 100 patient-years was higher in patients with SpA. Mean number of AU attacks per year was also higher in the first study group, but differences between the groups were statistically insignificant. CONCLUSION: Retrospective analysis of 189 patients with AU associated with HLA-B27 antigen revealed significantly higher frequency of complications, together with more frequent acute episodes in patients with SpA in comparison with patients without it confirming the notion that a systemic inflammatory disease can influence the severity of the course of AU.

[Spondyloarthritis: modern terminology and definitions].

Aim to identify outdated terms and make changes to the terminology of spondyloarthritis. MATERIALS AND METHODS: At the first stage of the work, the terms divided into two categories: "outdated" definitions and terms that need to be improved or unified. Subsequently, each member of the Expert Group of Spondyloarthritis at the Association of Rheumatologists of Russia (ExSpA) presented by its own definition of the designated term or agreed with the previous term. At the next stage, the existing definitions were put together. After discussion, experts left a term that scored at least 2/3 of the votes. The special opinion of experts was recorded, whose did not coincide with the majority opinion. An open vote was conducted, when defining an "outdated" term with the unanimous decision of all group members, this term was not recommended for further clinical use. RESULTS: The work carried out allowed us to identify a number of terms that are not recommended for use in clinical practice. Number of terms are defined, which should be used when discussing the problem of spondyloarthritis. CONCLUSION: The Expert Group of Spondyloarthritis at the Association of Rheumatologists of Russia suggests using or, accordingly, not using a number of terms and their definitions in clinical practice.

[Application of TNF-alpha inhibitors in treatment of uveitis associated with ankylosing spondylitis]. / Primenenie ingibitorov FNOα v terapii uveitov, assotsiirovannykh s ankiloziruiushchim spondilitom.

Uveitis is one of the most frequent extraskeletal manifestations of ankylosing spondylitis (AS). Despite iridocyclitis being the most prevalent form of uveitis in patients with AS, and the rareness of the involvement of posterior eye segments in the inflammatory process, the frequent exacerbation of the disease, a significant number of patients develop complications that lead to decrease of visual acuity. The review features theoretical prerequisites for application of tumor necrosis factor alpha (TNF-alpha) inhibitors: infliximab, adalimumab and etanercept. Literature data speaks for high efficacy of TNF-alpha inhibitors in prevention and arrest of uveitis onset in patients with AS.

[Uveitis-associated HLA class 1 histocompatibility antigens]. / Uveity i ikh assotsiatsiia s antigenami gistosovmestimosti klassa 1.

AIM: to evaluate the diagnostic and prognostic significance of HLA class 1 histocompatibility antigens in the development of anterior uveitis. MATERIAL AND METHODS: A total of 137 patients with anterior uveitis followed up at the Research Institute of Eye Diseases in 2009-2016 were tested for HLA antigens (A and B loci). The average patient's age was 29±12.4 years. All patients underwent a thorough medical interview with clinical and laboratory assessment. In case of suspected association with systemic disease, the patients were referred for consultation at the V.A. Nasonova Research Institute of Rheumatology. HLA typing was performed using a standard microlymphocytotoxicity test with specific anti-HLA sera (production of Gisans CC, Saint Petersburg). Statistical processing was performed with Statistica 6.0 software by applying methods of descriptive and nonparametric statistics (Mann-Whitney test). RESULTS: The results of HLA class 1 typing indicated a significant positive association between uveitis and the HLA-B27 antigen (p<0.00001). Moreover, there was a trend toward decreased frequencies of В7, B12, and B21 antigens (p=0.1), however, the changes were not statistically significant as compared to the control group. Other HLA class 1 antigens also did not differ significantly in frequency between uveitis patients and the controls. CONCLUSION: The study has confirmed an association between certain histocompatibility antigens and systemic diseases. However, a statistically reliable relationship has been established only for the HLA-B27 antigen.

[Uveitis in spondyloarthritis patients and its association with HLA-B27 histocompatibility antigen: prospective study]. / Prospektivnoe issledovanie uveitov pri spondiloartritakh i ikh assotsiatsii s antigenom gistosovmestimosti HLA-V27.

AIM: to perform a prospective study of clinical presentation and course of uveitis in spondyloarthritis (SpA) patients as well as its association with the HLA-B27 histocompatibility antigen. MATERIAL AND METHODS: The study included 219 patients with uveitis, all tested for HLA-B27 antigen and various infections (viral, bacterial, and parasitic) as well as examined for locomotive system involvement. RESULTS: The presence of the HLA-B27 antigen was determined in 142 (64.8%) out of 219 patients, of them 87 were diagnosed with an entity of the SpA group. The remaining 77 (35.2%) patients appeared to be HLA-B27-negative, but 13 were still diagnosed with an entity of the SpA group. There were 10 (4.6%) patients with 2 or more diseases from the SpA group («clinical decussation¼). When comparing the two groups of HLA-B27-positive and negative patients having both SpA and uveitis, no statistically significant difference was found as to the age of onset, site, frequency of attacks, and uni- or bilateral involvement (p>0.05). We also performed a comparison of HLA-B27-positive and negative patients with no account to their SpA status and revealed a higher complication rate in those that were «negative¼ (p<0.0001), which can be explained by the fact that HLA-B27-negative patients often have autoimmune or infectious uveitis of different origin notable for long attacks and short remissions. CONCLUSION: Assessing the site and course of uveitis as well as HLA-B27 testing of uveitis patients has proved important for etiological diagnosis. Diseases of the SpA group have been shown to be 6.7 times more common in HLA-B27-positive patients as compared to HLA-B27-negative ones. Clinical presentation of uveitis in the presence of SpA in both HLA-B27-positive and negative patients resembles that of idiopathic uveitis - an independent HLA-B27-associated syndrome (р>0.05). Cases of «decussation¼ between entities of the SpA group are usually more severe in terms of clinical presentation and course of uveitis and are associated with a worse prognosis. Complications of uveitis are more likely to be found in non-SpA HLA-B27-negative patients (р<0.0001).

[HLA-B27-associated uveitis].

The presented literature review discusses the etiology, pathogenesis, clinical picture, current diagnosis, and treatment of uveitis associated with HLA-B27 antigens.

[Diagnosis and treatment of HLA-B27-associated uveitis].

The purpose of the present investigation was to diagnose and to treat HLA-B27 antigen-associated uveitis in 102 patients (118 eyes) with anterior and posterior uveitis. HLA antigens were typed to specify the etiopathogenesis of uveitis. Along with this, the patients were examined by a rheumatologist, a rontgenologist, an immunologist, an urologist, a dermatovenereologist, a dentist, and an otorhinolaryngologist. The conventional ophthalmological study and eye B-scanning were also performed. After complex therapy, there were improvements in the ocular state and overall somatic condition, as confirmed by the results of clinical studies. In 81 patients, the time of relapses reduced and the duration of remissions increased; persistent remission occurred in 15 patients. The course of the disease was unchanged in 7 cases. The pathogenetic role of B-27 antigen in the development of uveitis, as well as ankylosing spondylarthritis, seronegative spondylarthropathy, and other types of spondyloarthritis has not been explained so far. Notwithstanding this, the joint efforts of an oculist, a rheumatologist, and, not rarely, other specialists and the specific features of a clinical approach could provide a pronounced positive effect in treating the patients with HLA-27-associated uveitis.

[Results of leflunomide treatment of psoriatic arthritis].

AIM: To study efficacy and tolerance of leflunomide (LF) in patients with polyarticular psoriatic arthritis (PsA). MATERIAL AND METHODS: The analysis was made in 58 patients: 35 (60%) females, 23 (40%) males. Mean age of the patients was 44.9 +/- 10.8 years, PsA duration--9.7 +/- 7.5 years. LF was given by a standard scheme: 100 mg/day for 3 days then 20 mg/day for 6 months. PsA activity was assessed by the number of painful and inflamed joints, pain intensity, VAS, Likert quastionnaire data. Functional status of the patients was estimated according to Health Assessment Questionnaire. Skin syndrome was rated by pruritus scale, 5-score Likert scale and PASI (psoriasis Area and Severity Index). PASI was applied in patients with affected area 3% at least. Quality of life was assessed by Dermatology Life Quality Index. Basic criterion of the treatment efficacy was response by PsARC (Psoriatic Arthritis Response Criteria). The additional evaluation was made of the number of patients with improvement by criteria ACR 20, ACR 50 and ACR 75 as well as those with 50 and 75% response by PASI (PASI 50 and PASI 75). RESULTS: To the end of the treatment the number of painful and inflamed joints decreased significantly (p < 0.001) as well as pain, VAS and Likert scores. To the treatment month 6 HAQ index diminished by 36%. According to PsARC, of 58 patients 36 (62%) patients responded. Improvement by ACR 20 was observed in 34 (59%) of 58 patients. PASI changes were not significant (p = 0. 144). DLQI diminished by 36% (p = 0.028). As shown by acute phase indices, LF had no effect on ESR (p = 0.45). CRP fell significantly to treatment month 3 (p < or = 0.001) and further changes were insignificant. LF tolerance was satisfactory. Ten patients (17%) withdrew because of side effects which were standard. Severe myelo- and hepatotoxicity were absent. CONCLUSION: LF is highly effective in therapy of polyarticular PsA and has satisfactory tolerance. Perspectives of further use of LF in combined treatment of PsA are associated with its potential to inhibit the disease progression.

[The clinico-genetic characteristics of combined forms of seronegative spondylarthritis]. / Kliniko-geneticheskie osobennosti sochetannykh form seronegativnykh spondiloartritov.

The authors present the results of clinico-genetic investigations made in 124 patients with combined forms of seronegative spondylarthritis. The combined and isolated forms are compared clinically. HLA-typing results are analysed.