Vol 90, No 5 (2018)


Atherosclerosis: perspectives of anti-inflammatory therapy

Nasonov E.L., Popkova T.V.


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.
Terapevticheskii arkhiv. 2018;90(5):4-12
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Diagnostic algorithm for antineutrophil cytoplasmic antibody-associated systemic vasculitis

Beketova T.V.


Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) are rare autoimmune disorders and characterized by severe multiple organ lesions with a potential fatal outcome. AAV comprises granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Early diagnosis and treatment can significantly improve the AAV prognosis, but there are can be difficult, largely due to the lack of criteria for the classification MPA, whose main difference is the absence of granulomatous inflammation. The presented paper deals with the results of the analysis of 251 patients with AAV (mean age 43.1 ± 15.9 years, men 40%, disease duration 3 (0,2-28,5) years, ANCA 100%), based on which the diagnostic algorithm was developed. The algorithm steps include classification criteria of EGPA as well as surrogate markers for granulomatous inflammation (SG) and vasculitis (SV). MPA confirmed by the absence of criteria for EGPA, the presence of SV and the absence of SG. Due to the algorithm usage, nosological affiliation of AAV was determined in 99% patients. Both GPA and MPA were the most common (53% and 37%), while EGPA was rare (9%). In MPA group the overall mortality was higher (18%) than GPA and EGPA (7-5%), p=0.003. In MPA with anti-proteinase 3 antibody the two-year survival rate was lower than those with anti-myeloperoxidase antibody (p=0.04), mainly because of the high risk for alveolar hemorrhage and rapidly progressive glomerulonephritis. Relapses occurred more frequently in EGPA (80%) and in GPA (64%) and less frequently in MPA (49%). The group differences confirm diagnostic value of the algorithm. In conclusion, the proposed algorithm will help to improve the diagnosis of AAV. It is important that crucial in the AAV diagnosis belongs focused and systematic clinical examination of patients.
Terapevticheskii arkhiv. 2018;90(5):13-21
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Results of one-year treat-to-target strategy in early psoriatic arthritis: data of an open-label REMARCA study

Korotaeva T.V., Loginova E.Y., Getiya T.S., Nasonov E.L.


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.
Terapevticheskii arkhiv. 2018;90(5):22-29
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Comparative analysis of anxiety-depressive spectrum disorders in patients with rheumatic diseases

Lisitsyna T.A., Veltishchev D.Y., Seravina O.F., Kovalevskaya O.B., Starovoytova M.N., Desinova O.V., Abramkin A.A., Ovcharov P.S., Vasil’ev V.I., Alekberova Z.S., Krasnov V.N., Nasonov E.L.


Research objective - comparative analysis of incidence and structure of anxiety-depressive spectrum disorders (ADD) in patients with various rheumatic diseases (RD). Materials and methods. 613 patients with RD were enrolled in the study: 180 with a reliable diagnosis of systemic lupus erythematosus (SLE), 128 with rheumatoid arthritis (RA), 110 with systemic sclerosis (SSc), 115 with Behcet's disease (BD), 80 with primary Sjögren's syndrome (pSS). Female prevailed in all groups (95% of patients with pSS, 88,2% - SSc, 87,2% - RA, 85,5% of SLE) except BD patients (70% male). The mean age was 42.3±1.54 years and was lower in patients with BD (33.3±0.98 years) and SLE (34.6±0.93 years) compared to patients with SSc (49.9±2.47 years), RA (47.4±0.99 years) and pSS (46.2±2.3 years). The mean RD duration was 130,0±8,65 months and was more at BD - 148,5±10,4 months, pSS - 141,6±8,92 months, RA - 138,4±10,1months, and less at SLE - 134,9±8,8 months and SSc - 87,0±5,04 months. The mean SLE activity index SLEDAI was 9,13±0,63 points (high), RA (DAS28) - 5,26±0,17 points (high), BD (BDCAF) - 3,79±0,2 points (moderate) and SSc by G. Valentini - 1,1±0,20 points (moderate). Glucocorticoids took 100% of patients with pSS, 91,1% - SLE, 90% - SSc, 87% - BD and 67,2% - RA patients; conventional disease modifying anti-rheumatic drugs (cDMARDs) took 90% of patients with SSc, 84% - BD, 79,6% - RA, 68% - pSS, 40,6% - SLE. Biologic DMARDs took 32% of patients with RA, 17,4% - BD, 7,3% - SSc and 7,2% - SLE. Mental disorders were diagnosed by psychiatrist as a result of screening by the hospital anxiety and depression scale (HADS) and in semi-structured interview in accordance with the ICD-10/ DSM-IV. The severity of depression was evaluated by Montgomery-Asberg Depression Rating Scale (MADRS) and anxiety - by Hamilton Anxiety Rating Scale (HAM-A). Projective psychological methods were used for cognitive impairment detection. Results. Screening of depressive disorders (HADS-D≥8) was positive in 180 (29,4%) patients with RD, including 74 (41%) patients with SLE, 38 (35%) - SSc, 29 (23%) - RA, 23 (20%) - BD and 16 (20%) - pSS; anxiety disorders (HADS-A≥8) - in 272 (44,4%) patients, including 66 (52%) patients with RA, 40 (50%) - pSS, 77 (43%) - SLE, 45 (41%) - SSc and 44 (38%) - BD. In accordance with the ICD-10/ DSM-IV depressive disorders have been identified in 389 (63%) patients, including 94 (73%) patients with RA, 71 (64,5%) - SSc, 69 (60%) - BD, 90 (50%) - SLE and 39 (49%) - pSS; anxiety disorders - in 377 (61,5%) patients, including 20 (25%) patients with pSS, 44 (24,5%) - SLE, 29 (23%) - RA, 20 (17%) - BD and 7 (6,4%) - SSc. Conclusion. Anxiety-depressive spectrum disorders are typical for most patients with RA, SLE, SSc, pSS and BD. ADDs diagnosis in RD patients with the use of the HADS did not reveal a significant proportion. To obtain objective data on the frequency and structure of ADDs, psychopathological and clinical psychological diagnosis is necessary.
Terapevticheskii arkhiv. 2018;90(5):30-37
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Association of polymorphisms of HLA-DRB1 and TNF-308 G/A with radiographic joint damage in patients with early rheumatoid arthritis with high inflammatory activity, treated according to the principle of “Treat to target” (REMARKA study)

Guseva I.A., Smirnov A.V., Demidova N.V., Krylov M.Y., Avdeeva A.S., Samarkina E.Y., Luchikhina E.L., Karateev D.E., Abramov D.D., Nasonov E.L.


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.
Terapevticheskii arkhiv. 2018;90(5):38-43
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Efficacy and tolerability of abatacept treatment: results of 12 months observation

Borisova M.A., Lukina G.V., Sigidin Y.A., Aronova E.S., Luchihina E.L., Karateev D.E., Glukhova S.V., Nasonov E.L.


Objectives: This article reports 1-year clinical outcomes of patients with rheumatoid arthritis (RA) receiving abatacept (ABA) therapy. Materials and methods: Patients (n=91) with high RA activity (DAS28 = 5.1 ± 1.0) and an inadequate response on synthetic DMARDs (mainly methotrexate, 70.3%) and biologics (mainly TNF-α inhibitors, 93%) were included in the study. The majority of patients were middle-aged (49 ± 13.5) womens, RF (72.5%) and ACPA (77%) positive, with moderate functional impairment - HAQ = 1.4 (0.9-2). ABA were administered IV, 10 mg/kg according to the standard scheme. The evaluation of the effectiveness of the therapy was carried out according to the EULAR / ACR 2011 criteria using SDAI, CDAI, HAQ and the intention to treat approach. Results: ABA led to a significant (p <0.05) decrease activity of RA. Clinical improvement according to EULAR criteria after 6 months of treatment was registered in 70.9%, after 12 months 63%. Almost a third of patients (28.7%) achieved a good response after 3 months of therapy, 39,2% - after 6 months and 39% - after 12 months. The retention rate of ABA therapy after 6 months was 77%, after 12 months - 60%. There were no significant differences between "bio-naive", 1 Bio and ≥2 Bio groups in achieving EULAR response. A good response was achieved in 38%, 38% and 43%, respectively, but the lowest number of non-responders was registered in ≥2 Bio - 38%, 36% and 43%. ABA significantly improved functional status of patients, after 12 months a marked and moderate improvement in the HAQ was achieved in 39% and 21% of patients, respectively. Adverse events (AE) were registered in 22 patients. The most frequent AE were upper respiratory tract infections - 11 (12%) patients. Conclusion: Abatacept was effective in the overall population, and in all subgroups of patients. It has shown significant improvement of clinical and functional status in patients who had an inadequate response to previous therapy. ABA has a good safety profile. AE were registered only in a small number of patients.
Terapevticheskii arkhiv. 2018;90(5):44-49
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Do glucocorticoids affect the development of ulcers and erosions of the upper gastrointestinal tract in patients taking NSAIDs?

Karateev A.E., Moroz E.V.


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.
Terapevticheskii arkhiv. 2018;90(5):50-54
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Panniculitis in rheumatology: features of course and outcomes

Savushkina N.M., Egorova O.N., Glukhova S.I., Belov B.S.


Objective. The study of the course and outcomes of panniculitis (PN) in modern rheumatology practice. Patients and methods. We observed 209 patients (pts) (f-185, m-24 in age 17 to 80 years) with the input diagnosis "Erythema nodosum? Undifferentiated panniculitis?" and duration of illness in from 1 week to 25 years, observed in V.A. Nasonova Research Institute of Rheumatology in 2009-2016 years. Along with the general clinical examination, serological, immunological histological and immunohistochemical studies, CT scan of the chest, Doppler (Doppler ultrasound) of the veins of the lower extremities, tuberculin tests and consultations with doctors of other specialties were conducted. Outcomes were assessed after 1-6 years. Results. In 23 pts a secondary character of PN was identified and discovered non-rheumatic underlying disease. Of the remaining 186 cases, the most frequent were pts with erythema nodosum (EN) (n=121), lipodermatosclerosis (LDS) (n=38) and panniculitis of Weber-Christian (PWCh)(n=18). For EN average age (AA) amounted to 38.9±12.6 years, the nodes the nodes were located symmetrically in 93% of cases on all surfaces of the lower and upper extremities (LUE). For LDS AA of the pts was 54±13 years, 68% of the pts noted the increase in the average body mass index (BMI), 79% - showed signs of chronic venous insufficiency (CVI). In 60% of the pts the items were located asymmetrically, localized mainly in the medial (92%) of the surface of the tibia (s). For PWCh AA amounted to 48.4 ± 17.6 years, seals were located on all surfaces of LUE and in 14 cases - on the trunk. Conclusion. To clarify the nature of PN it is necessary to conduct a comprehensive survey. The EN is characterized by symmetric defeat of all surfaces LUE more common in people of young age. A distinctive feature of LDS is asymmetrical lesions of the lower extremities in patients with increased BMI and signs of CVI. For PWCh seals are often localized on the trunk.
Terapevticheskii arkhiv. 2018;90(5):55-60
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Diagnosis of IgG4 - related ophthalmic disease in a group of patients with various lesions of the eye and orbits

Vasilyev V.I., Safonova T.N., Socol E.V., Probatova N.A., Kokosadze N.V., Pavlovskaya A.I., Kovrigina A.M., Radenska-Lopovok S.G., Gorodetsky V.R., Rodionova E.B., Palshina S.G., Aleksandrova E.N., Shornikova N.S., Gaiduk I.V.


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.
Terapevticheskii arkhiv. 2018;90(5):61-71
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DICER and DROSHA gene expression in peripheral mononuclear blood cells from rheumatoid arthritis patients under methotrexate therapy

Malysheva I.E., Topchieva L.V., Balan O.V., Marusenko I.M., Barysheva O.Y.


The aim of this research was studying the level of DROSHA and DICER genes expression in peripheral mononuclear blood cells (PBMC) in rheumatoid arthritis (RA) patients under methotrexate therapy. Materials and methods. 82 people (from 45 to 70 years) enrolled in this study were divided into 3 groups (the first one - healthy donors (n=33 median age 49.93±1.87); the second group - rheumatoid arthritis patients without any therapy (n=15; median age 57.28±15.18) and the third group (n=34; median age 60.88±9.02) - rheumatoid arthritis patients who treated at least 4 weeks with methotrexate therapy (10-20 mg/week). The DICER and DROSHA genes expression level was determined by real-time PCR. Results. The number of DICER gene transcripts in PBMC in rheumatoid arthritis patients without therapy as in RA patients treated with methotrexate was reduced in comparison with the healthy donors (p<0.001 and p>0.05 respectively). The level of DROSHA gene expression in PBMC was not significantly different in all groups enrolled in this study (p>0.05). Conclusion. Our findings suggest that that the DICER gene expression level in perifheral mononuclear blood cells decreased with the development of rheumatoid arthritis. Methotrexate doesn’t influence on the mRNA level of this gene.
Terapevticheskii arkhiv. 2018;90(5):72-75
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The efficacy of rituximab in the therapy of neuromyelitis optica in a patient with Sjogren's syndrome: case-report and literature review

Torgashina A.V., Vasilyev V.I.


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.
Terapevticheskii arkhiv. 2018;90(5):76-80
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Use of a glycosamine sulfate for patients with osteoarthritis and a comorbidity with high risk of the side effects from NSAIDS

Naumov A.V., Tkacheva O.N.


The literature review is devoted to the peculiarities of treating co-morbid patients with acute conditions of chronic pain. The proved effect of NSAIDS must always correlate with the side effect risk. Patented microcrystalline glucosamine sulfate (pCGS) is likely to have an effect similar to NSAIDS because it can cause decrease of COX-2 and PGE2 gene expression. Randomized trials show, that patented microcrystalline glucosamine sulfate can impede complex structure changes and have a positive effect on the symptoms at the early stage of knee OA. Pharmacokinetic evidence demonstrates that repeated oral intake of microcrystalline glucosamine sulfate can cause the increase of GS in synovial fluid. It is necessary to monitor OA biomarkers during microcrystalline GS treatment, recommend appropriate physical exercise and study the neuropathic component of chronic pain.
Terapevticheskii arkhiv. 2018;90(5):81-87
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Gout. New opportunities of diagnosis and treatment

Yakupova S.P.


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.
Terapevticheskii arkhiv. 2018;90(5):88-92
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High resolution manometry and new classification of esophageal motility disorders

Ivashkin V.T., Maev I.V., Trukhmanov A.S., Storonova O.A., Kucheryavyi Y.A., Barkalova E.V., Ovsepyan M.A., Andreev D.N., Paraskevova A.B., Rumyantseva D.E.


Purpose of the review. To present application of Chicago classification criteria of esophageal motility disorders defined in high resolution manometry in clinical practice. Basic provisions. High-resolution manometry is the most exact hi-tech diagnostic method for esophageal motor function disorders according to Chicago classification v3.0. Uniqueness of the method consists in capacity to define integrated quantitative and qualitative metrics of esophageal contractile function and to establish their specific disorders e.g.: change of intrabolus pressure at disorders of esophagogastric junction (EGj) outflow, hypercontractile esophagus, fragmented contractions and weak or failed peristalsis, distal esophageal spasm. Assessment of the type of achalasia subtypes has significant impact on the patients’ treatment choice. According to anatomical location of the lower esophageal sphincter and crural diaphragm several morphological types of gastro-esophageal junction are defined that determine severity of gastroesophageal reflux disease. Multiple rapid swallow responses during esophageal high-resolution manometry reflect esophageal body peristaltic reserve and is a predictor of postoperative complications. Differential diagnosis of belching type became possible at combined application of high-resolution manometry and impedance measurement. Conclusion. High-resolution manometry is a fundamental diagnostic test of esophageal motor function disorders. Clinical application of this method significantly expands diagnostic potential and allows to carry out personalized treatment that increases treatment quality.
Terapevticheskii arkhiv. 2018;90(5):93-100
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