[Non-infectious diseases of the aorta and large arteries].

This article describes the various forms of inflammatory lesions of the aorta and large arteries, including chronic periaortitis, as well as the diagnostic methods are considered. Large vessel vasculitis represent the most common entities, however, there is also an association with other rheumatological or inflammatory diseases, drug-induced or paraneoplastic entities. Instrumental imaging modalities play an important role in the diagnosis.

[Possibility of complex medicamental and endovascular treatment of pulmonary hypertension in Takayasu arteritis with predominant pulmonary arteries' lesion].

Takayasu arteritis (TA) is a systemic vasculitis with predominatly lesions of aorta and its large branches. In some cases pulmonary arteries (PA) are involved in the pathological inflammatory process and lead to the formation of pulmonary hypertension and significantly worse the prognosis. Timely development of lesion of PA, appointment of adequate therapy and surgical treatment can prevent irreversible damage of blood vessels and improve the prognosis. Perioperative administration of interleukin-6 inhibitor inhibitor (tocilizumab) in at patients with indications for vascular surgery, including angioplasty PA, should be considered as a promising approach to control the inflammatory activity of TA, reduce the dose of glucocorticoids and the risk of postoperative complications. We present the clinical experience of significant improvement in the patients condition was achieved by using two-stage balloon angioplasty on the background of control of the disease activity with interleukin-6 tocilizumab intravenously and specific therapy with riociguat and iloprost.

[Pulmonary hemorrhage in rheumatic diseases].

In the article, we report the causes of pulmonary hemorrhage (PH) according to the literature data and own experience, with an emphasis on patients suffering from rheumatic diseases. Methods of diagnosis and modern approaches to the treatment of PH are analyzed.

Diagnostic algorithm for antineutrophil cytoplasmic antibody-associated systemic vasculitis.

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.

[Hepatitis C virus-associated cryoglobulinemic vasculitis: A 20-year experience with treatment]. / Krioglobulinemicheskii vaskulit, assotsiirovannyi s virusom gepatita S: 20-letnii opyt lecheniia.

AIM: To summarize the experience of a multidisciplinary therapy hospital in treating patients with hepatitis C virus (HCV)-associated cryoglobulinemic vasculitis (CV). SUBJECTS AND METHODS: Seventy-two patients (mean age, 49.4±10.3 years) with HCV-associated CV were examined and followed up for an average period of 2.8±3.6 years. The efficiency of traditional (corticosteroids ± cyclophosphamide) and selective (rituximab) immunosuppressive therapy (IST) was estimated in 31 and 15 observations, respectively, and that of antiviral therapy (AVT) in 25. Vasculitis activity was assessed using the Birmingham vasculitis activity score (BVAS). The patients' survival was studied; multivariate logistic regression analysis was carried out. RESULTS: 24 (33.4%) of the 72 patients had a stage of liver cirrhosis (LC). The pretreatment mean BVAS was 11.9±7.2 (range 2 to 36). Severe CV (BVAS ≥15) was present in 30.6% of the patients. AVT was accompanied by achievement of sustained virologic response in 48% of the patients, clinical remission in 68% and had an advantage over IST in relation to long-term treatment results. Rituximab was significantly more effective than traditional immunosuppressants (remission rates of 73 and 13%, respectively). Combined therapy (rituximab and AVT) was most effective in patients with severe forms of vasculitis. Sixteen patients died from complications of vasculitis (37.5%), infection (37.5%), and LC (25%). The factors adversely affecting prognosis were age >55 years (odds ratio (OR), 4.49), the presence of LC (OR, 3.68), renal failure (OR, 4.66) and the use of glucocorticosteroids (OR, 3.91). CONCLUSION: HCV-associated CV can determine the prognosis of chronic HСV infection. AVT is the treatment of choice in all patients with HСV-associated CV. AVT must be combined with rituximab therapy in patients with severe forms of vasculitis.

[Current approaches to diagnosing and treating eosinophilic granulomatosis with polyangiitis: The 2015 international guidelines].

The 2015 international guidelines for the diagnosis and treatment of eosinophilic granulomatosis with polyangiitis, formerly known as the Churg-Strauss syndrome, are detailed and an attempt is made to expand an evidence base, by attracting more recent available publications. The new guidelines should not be regarded as final standards; these are primarily to extend the possibilities of choosing a personified management strategy for patients with eosinophilic granulomatosis with polyangiitis and to serve as the starting point for further in-depth investigations.

[Microscopic polyangiitis associated with antineutrophil cytoplasmic antibodies: clinical features].

AIM: To study the clinical features of early- and extended-stage microscopic polyangiitis (MPA) and its outcomes on the basis of a long-term follow-up in a rheumatologist's practice. SUBJECTS AND METHODS: The clinical features of early- and extended-stage MPA were studied in detail and the premorbid background and possible precipitating factors were analyzed in 70 patients with MPA and the proven hyperproduction of antineutrophil cytoplasmic antibodies (anti-proteinase-3 (anti-PR3) antibodies in 55% and anti-myeloperoxidase (anti-MPO) antibodies in 45%) who had been followed up for more than a year. RESULTS: There is evidence for the nosological unity of the two immunological types of MPA associated with anti-PR-3 or anti-MPO antibodies. MPA has been demonstrated to be an aggressive, polysyndromic disease prone to recurrences (52%), the typical manifestation of which is glomerulonephritis (94%) that is rapidly progressive in every four cases and accompanied by hemorrhagic alveolitis (69%) and involvement of other organs. ENT organs and lungs have been noted to be commonly involved in early-stage MPA, which was observed in 61% of the patients in the premorbid period, and to become the first manifestation of MPA (63%) concurrent with body temperature rises (64%), arthralgia or arthritis (41%). Respiratory tract involvement in MPA may be asymptomatic. Anti-PR-3-associated MPA may manifest itself more aggressively and in the first 2 years it is characterized by a poorer prognosis than of anti-MPO-associated MPA (survival rates, 82 and 94%, respectively; p = 0.04). With time, the differences were levelled off; recurrences in the patients with anti-PR-3 and anti-MPO develop equally frequently and proceed showing the similar clinical picture; the survival curves converge by age 3. Anti-MPO-associated MPA is characterized by the highest rate of lung involvement in the clinical phase of the disease (61%) and by a propensity to develop hemorrhagic alveolitis, diffuse interstitial (22%) or circumscribed pulmonary fibrosis in the outcome. CONCLUSION. The findings emphasize how important to diagnose MPA early and to prescribe long-term active treatment using the entire current arsenal of medications as soon as possible until severe injury to organs and systems develops. To specify regularities in the development of MPA may be of value for the better diagnosis of the disease and the further elaboration of optimal treatment policy.

[The current classification of systemic vasculitides].

Systemic vasculitides (SV) are severe multiorgan diseases whose early diagnosis and treatment can significantly improve prognosis. Improving the classification of SV may lead to a significant reduction in the likelihood of diagnostic errors. The presented paper deals with the results of the International Consensus Conference on the Nomenclature of SV (Chappel Hill, USA) in 2012. The nomenclature and definitions of the major forms of SV were revised and additional categories of vasculitis were included into the classification, by relying on the current trends in the practical use of terms, on the current ideas on the specific features of manifestations of diseases, and on achievements in studying the pathogenesis.

[Antibodies to proteinase-3 and myeloperoxidase in systemic vasculitis]. / Antitela k proteinaze-3 i mieloperoksidaze pri sistemnykh vaskulitakh.

AIM: To investigate occurrence and diagnostic significance of antibodies to proteinase-3 (aPR-3) and myeloperoxidase (aMPO) in systemic vasculitis (SV). MATERIAL AND METHODS: A total of 98 patients with different forms of SV were examined: nonspecific aortoarteritis (NAA, n = 18), nodular polyarteritis (NP, n = 18), Wegener granulomatosis (WG, n = 20), obliterating thrombangiitis (OT, n = 21), and hemorrhagic vasculitis (HV, n = 21). Eight patients with primary antiphospholipid syndrome (PAPS) and 20 donors comprised a control group. aPR-3 and aMPO were detected by solid-phase enzyme immunoassay using kits ORGenTec Diagnostica GmbH. RESULTS: aPR-3 were detected in 1 (5.6%) patient with NP and in 3 (14.3%) patients with HV. aPR-3 were detected in 13 (65%) of 20 patients with WG being significantly more frequent not only vs controls (0%) but in some forms of SV and PAPS (p < 0.05). Mean aPR-3 level in 13 WG patients was significantly higher than in 4 patients (1 with NP and 3 with HV) the sera of whom also contained aPR-3. 84.6% patients with WG had higher concentrations of aPR-3, this is significantly more frequently than in the comparison group. In NP and HV these autoantibodies were encountered in the serum only in moderate or low concentrations in patients with high clinicolaboratory activity of the disease. In WG patients there was no correlation between aPR-3 presence, form of the disease and basic clinical manifestations, but mean values of index of clinical activity of vasculitis were significantly higher in patients with aPR-3 than in those free of them. Concentration of aPR-3 in an active phase of the disease was significantly higher than in patients in remission. Moreover, aPR-3 were detected in 83.3% cases in active vasculitis and in 37.5% patients without it. Detection of aPR-3 in WG group was associated with mean sensitivity and good specificity. In examination of the patients in an active phase specificity rose but sensitivity fell. Optimal results were obtained in estimation of aPR-3 level. Thus, in moderate or high concentration, aPR-3 have good sensitivity and high specificity for diagnosis of WG, in a high titer (> 15 U/ml) they are highly sensitive and specific for this vasculitis. aMPO were detected in 1 of 18 patients with NP, in 1 of 21--with OT, in 3 of 21--with HV and in 2 of 21--with NAA. None patients with WG or PAPS had aMPO. aMPO were detected in NP and HV in high activity of inflammation. Part of the patients had affected kidneys. CONCLUSION: Thus, WG is characterized by the presence and high concentration of aPR-3. In the latter case aPR-3 have high (100%) sensitivity and specificity for diagnosis of WG. Detection of aPR-3 can be used as an additional laboratory test for diagnosis of WG and estimation of its activity.

Serum concentrations of neopterin, soluble interleukin 2 receptor, and soluble tumor necrosis factor receptor in Wegener's granulomatosis.

OBJECTIVE: To investigate the possible relationship between serum levels of neopterin, soluble tumor necrosis factor-55 receptor (sTNF-55R), and soluble interleukin 2 receptor (sIL-2R) with disease activity in patients with Wegener's granulomatosis (WG). METHODS: Serum neopterin was measured by radioimmunoassay, sTNF-55R and sIL-2R were measured by ELISA in 26 patients with WG. RESULTS: Serum neopterin, sTNF-55R, and sIL-2R were significantly elevated in patients with generalized WG compared with healthy controls. Concentrations of the analytes correlated with disease activity indices in patients without infectious complications. The highest elevations of all 3 variables were observed in patients with intercurrent infections. CONCLUSION: The increased serum levels of neopterin, sTNF-55R, and sIL-2R suggest activation of cellular immunity in WG.

[Clinical and pathogenetic aspects of kidney damage associated with neutrophilic cytoplasm antibodies]. / Klinicheskie i patogeneticheskie aspekty porazheniia pochek, sviazannogo s antitelami k tsitoplazme neitrofilov.

A retrospective analysis of the authors' own findings and foreign authors' data has demonstrated that neutrophilic cytoplasm antibodies (NCAs) play a definite pathogenetic role in the activation of neutrophils, a central link in the pathogenesis of vascular wall damage in necrotizing vasculitides. The clinical value of NCAs varies with their specificity. Proteinase 3 antibodies whose detection allows one to suppose Wegener's granulomatosis are of greater diagnostic value. Myeloperoxidase antibodies are revealed in various necrotizing vasculitides and promptly progressive glomerulonephritis and more infrequently in other diseases. Thus, the detection of antibodies to proteinase-3 and myeloperoxidase in the presence of appropriate clinical signs is most likely to diagnose primary necrotizing vasculitis. The changes in the levels of NCA reflect the activity of a renal processes and the progression of the whole disease.

[The current concepts of microscopic polyarteritis]. / Sovremennye predstavleniia o mikroskopicheskom poliarteriite.

Clinical picture, morphological changes, immunological disorders confirm reality and nosological independence of MPA. A clear nosological differentiation of systemic vasculitis is important for decision on an individual choice of treatment.