Vol 90, No 5 (2018)

According to modern ideas, chronic low-grade inflammation, which development is associated with uncontrolled activation of both innate and adaptive immunity, plays a fundamental role in all stages of the atherosclerotic process. The contribution of inflammation to the development of atherosclerotic vascular lesions attracts attention to the similarity of the mechanisms of immunopathogenesis of atherosclerosis and classic inflammatory rheumatic disease - rheumatoid arthritis. In the aspect of participation in the pathogenesis of atherosclerotic vascular lesions and as a promising therapeutic "target" of particular interest is interleukin-1β (IL-1β), which plays an important role in the development of many acute and chronic immunosuppressive diseases. The mechanisms of atherosclerosis associated with IL-1β determine the ability of cholesterol crystals and other "Pro-atherogenic" factors to induce the synthesis of IL-1β by activating NLRP3 inflammasome. The mechanisms of atherosclerosis associated with IL-1β determine the ability of cholesterol crystals and other "proatherogenic" factors to induce the synthesis of IL-1β by activating NLRP3 inflammasome. Convincing evidence for the role of inflammation in development of atherosclerosis in General and good prospects of anti-inflammatory therapy in particular obtained in a randomized placebo-controlled study called CANTOS (Canakinumab Anti-inflammatory Thrombosis Otcomes Study), which studied the effectiveness of treatment with monoclonal antibodies to IL-1β canakinumab (Novartis International AG) in patients with severe atherosclerotic vascular lesions as a new approach to secondary prevention of cardiovascular complications. The results of CАNTOS research, as well as the experience gained in rheumatology in regard to cardiovascular effects of innovative anti-inflammatory drugs, have great importance for the improvement of secondary prevention of atherosclerosis-related cardiovascular complications.

Objectives: to study efficacy of treat-to-target (T2T) strategy in early peripheral psoriatic arthritis (EPsA) after one year of treatment. Methods: 44 (M/F - 18/26) DMARD-naїve patients (pts) with active EPsA, according to the CASPAR criteria, mean age 37.5±11.3 years, PsA duration 7 [4; 24] months, psoriasis duration 36 [12; 84] months, disease activity index (DAS) 3.78 [3.18; 4.67], DAS28 4.33 [3.67; 4.8] study were included. At the baseline and every other 3 months for total 12 months of therapy all pts underwent standard clinical examination, tender joint count (TJC), swollen joint count (SJC), patient pain VAS, patient/physician´s global disease activity VAS, enthesitis by Leeds Enthesial Index (LEI)+Plantar Fascia (PF), dactylitis, Psoriasis Area Severity Index (PASI), body surface area (BSA), Health Assessment Questionnaire (HAQ), DAS, DAS28-C-RP, C-RP (mg/l). The dose of MTX s/c was escalated by 5 mg every 2 weeks from 10 mg/wk to appropriate dose 20-25 mg/wk according to the drug intolerance. If pts does not achieve the lower disease activity (LDA), MDA or remission after 3 months of MTX subcutaneous (s/c) mono-therapy, then combination therapy of MTX+Adalimumab (ADA) by standard regime was continued up to one year. At 12 months of therapy the proportion of pts who attained LDA by DAS/DAS28 or remission by DAS<1.6/DAS28-C-RP<2.6 or MDA, ACR20/50/70, PASI75 and dynamics of HAQ, LEI+PF, dactylitis were calculated. Mean±SD, Me [Q25; Q75], %, Friedman (Fr.) ANOVA, U-test, Wilcoxon test were performed. All p<0.05 were considered to indicate statistical significance. Results: At one year of treatment according to T2T strategy significant improvements disease activity and physical health function related to quality of life was seen. By 12 months of therapy remission by DAS and MDA was reached 61.4%/65.9% of pts accordingly. By 12 months of therapy ACR20/50/70 was seen in 88%/77%/59% of pts. In pts with BSA≥3% (n=16) at baseline psoriasis improvements by PASI75 was seen in 88% of pts. In 55% of active EPsA pts MTX (s/c) mono-therapy was an effective treatment. Conclusions: One-year treatment according to T2T strategy significantly improves all PsA clinical domains - arthritis, dactylitis, enthesitis, skin psoriasis and quality of life despite of type of treatment. It seems that T2T is a useful strategy in EPsA but additional research concerning its implementation in real practice are needed.

Objective. To clarify the association between HLA-DRB1 and TNFα (-308G>A) genes polymorphism and joint destruction/further progression during 12 months of the follow-up period (FUP) in patients with early (<6 months), active, predominantly antibodies to cyclic citrullinated peptide (ACCP) and rheumatoid factor (RF)-positive rheumatoid arthritis (RA) treated according to "Treat to target" strategy. Materials and Methods. The study included 85 patients with early RA and duration of symptoms <6 months. All patients were initially assigned to subcutaneous methotrexate (MTX) with rapid dose escalation to 20-25 mg/week. Combination MTX + biological therapy, mainly adalimumab, was used when MTX was ineffective. Joint destruction was assessed by Sharp-Van der Heijde modification scoring method at baseline and after 12 months FUP. Real time polymerase chain reaction (PCR-RT) was used for TNFα gene polymorphism (-308G>A) genotyping. Low resolution PCR-RT with subsequent sequence-based typing of *04 were performed to study HLA-DRB1 gene polymorphism. The HLA-DRB1*01, *04:01, *04:04, *04:05, *04:08, *10 alleles were categorized as SE+ (Shared Epitope) alleles. Results. As for TNFα gene polymorphism, it was demonstrated that the number of narrowings and total Sharp score values were almost twice as high at baseline in GG genotype carriers as compared to GA genotype carriers (р<0,005, and р<0,004 respectively). Similar association was found after 12mo FUP. The progression of joint destruction, assessed as the change (∆) in the number of erosions, joint space narrowings and the total score, was statistically significantly associated with HLA-DRB1*(SE) genotypes: the carriers of SE (SE+/SE+) double-dose had more advanced progression as compared to (SE+/SE-)/(SE-/SE-) carriers (р<0,028, р<0,019, р<0,035 respectively). Conclusion. Our data suggest that HLA-DRB1 (SE+) gene and TNFα (-308G>A) polymorphisms are associated with the progression of radiographic joint destruction in early, active RA patients managed according to "Treat to target" stratagy.

The use of glucocorticoids (GC) is considered one of the risk factors for the development of gastro-intestinal (GI) complications associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs). However, the data on this issue are contradictory. Objective. To assess the frequency of ulceration and erosion in patients with rheumatic diseases (RD) receiving NSAIDs, depending on the concomitant use of GC. Materials and methods. A retrospective comparison was made of the incidence of gastrointestinal lesions detected in patients with RD during endoscopic examination in one medical center for 2007-2016. Three groups were formed: in group 1 patients took only NSAIDs (n=4823, women 80.7%, age 51.1 + 15.4 years), in group 2 patients took NSAIDs and GC (n = 1608, women 89, 8%, age 50.4 + 14.6 years), in group 3 - only patients took GC (n=1135, women 92.7%, age 44.1 + 15.3 years). The detection of multiple erosions (>10, ME) and gastric and / or duodenal ulcers was as-sessed. Results. The frequency of ME and ulcers in patients of groups 1 and 2 did not differ significantly: 10.5% and 8.5%, odds ratio 0.799 (95% confidence interval 0.546-1.169, p=0.072). Risk factors, such as age > 65 years, ulcer history and low-dose aspirin, did not affect this pattern. The incidence of ME and ulcers was significantly lower in Group 3 patients than in Groups 1 and 2: 6.3% (p<0.001, p=0.032). The conclusion. The use of GC does not increase the risk of erosion and ulcers of the upper GI tract when taking NSAIDs.

Purpose of the study. To provide demographic, clinical, laboratory, ultrasound, radiological, morphological/ immunomorphological phenotype of IgG4-related ophthalmic diseases, which allowsmaking a differential diagnosis with granulomatous, autoimmune, inflammatory, endocrine and hematologic diseases affecting the eye and orbits. Materials and methods. From 2004 to 2016 108 (78.2%) of the 138 patients were diagnosed with non-tumoral lesions of eye and orbits. In 48 patients (35%) at admission and 5 patients in the follow were diagnosed IgG4-related ophthalmic disease. In the analysis of 82 (f-44, m-38) patients with IgG4-related disease, localization of lesions in orbit observed in 53 (f-36, m-17) and it was the most frequent involvement in patients with IgG4-related disease (64.5%). Only 7 patients had isolated IgG4-related ophthalmic disease, whereas 46 patients (87%) had involvement of 2-7 locations, as a manifestation of IgG4-related systemic disease.During the examination, the average age of patients with IgG4-related ophthalmic disease was 47.5 years (19-73 years). Median time to diagnosis was 52.8 months before 2004 and 36 months 2004-2016. Results. We noted the predominance of females in the ratio 2: 1 inthe group of patients with IgG4-related ophthalmic disease. Edema of the eyelids, nasal congestion (55-60%), tumor-like formations of the upper eyelids and increased lacrimation prevailed at the onset of the disease, whereas such functional impairment like limited mobility and pain in eyeballs, exophthalmos, ptosis and diplopia appeared later at 15-38% with a loss visual acuity in one case. Bilateral lesion (86%), mainly affecting the lacrimal glands (93.5%), infiltration of the extraocular muscles (83.5%) and retrobulbar tissue with a thickening of the optic nerve in one third of patients were the main localizations IgG4-related ophthalmic disease. Clinical symptoms were accompanied by the appearance of moderate inflammatory activity (38%), increased levels IgG (44%), IgG4(88%) and IgE (61%). Indicators of autoimmune disorders observed in 6-22% of patients, most often in patients with simultaneous involvement of the salivary glands. Significant lymphoplasmacytic infiltration (94%) with a ratio of plasma cells (IgG4/IgG) secreting IgG4> 40% (90%) with fibrosis formation (94%) and follicle formation (71%) with a moderate amount of eosinophils (34%) were the major morphological / immunomorphological manifestations of IgG4-related ophthalmic disease. Signs of vasculitis and obliterative phlebitis were found in a small amount of patients. Conclusion. Determination of elevated levels of IgG-4 / IgE in patients with edema, pseudotumor of the eyelid, sinusitis and increase of the palpebral lobe of the lacrimal gland suggests the presence of IgG4-related ophthalmic disease. Minimally invasive incisional biopsy of lacrimal glands and salivary glands followed by morphological / immunomorphological research is needed for the correct diagnosis. Diagnostic orbitotomy in ophthalmic hospitals in such cases is inexpedient, since it leads to the development of dry eye. Massive lymphoplasmacytic infiltration with IgG4 / IgG ratio more than 40%, advanced fibrosis in biopsiesof the orbits tissue or salivary glands when combined lesions are required for the making the diagnosis of IgG4-related ophthalmic disease.

This case is the first description of the successful anti-B-cell therapy with rituximab in a patient with Sjogrenʼs syndrome and neuromyelitis optica spectrum disorder in Russia. This article contains the literature data on clinical manifestations and methods of the diagnosis of neuromyelitis optica spectrum disorder. Furthermore, contemporary view on the pathogenesis of the combination of this disease with Sjogrenʼs syndrome are presented here.

In recent yearsincidences of gout has increased. Despite the current diagnostic possibilities, doctors face the difficultiesin establishing the diagnosis. In 2015new criteria of diagnosis of goutwere developed by European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR). In 2016 the EULARexpert group offered the treatment strategy of patients with gout. Main features of the strategy and new researches, revealing the most effective and safest possibilities for gout treatment were laid down in article.