[Severe adverse events from treatment with genetically engineered biological agents in patients with rheumatic diseases].

AIM: To assess the risk of severe adverse events (AEs) within 6 months after treatment with biological agents in patients with rheumatic diseases (RD). SUBJECTS AND METHODS: The 6-month open-label trial included 107 patients with rheumatoid arthritis, antineutrophil cytoplasmic antibody-associated vasculitides, systemic lupus erythematosus, and other RDs who received genetically engineered biological agents (GEBAs), primarily rituximab (n = 66) and infliximab (n = 31). RESULTS: The majority of patients were noted to have improvements, including complete and partial remission in 62 (57.9%) and 42 (39.3%), respectively. There were mild or moderate AEs in 22 (20.6%) of the 107 patients, severe AEs in 6 (5.6%): grade IV neutropenia in 2 patients (after the use of rituximab), severe infusion reactions in 2 (after the administration of infliximab and rituximab), and systemic infections in 2 (fatal nocardial sepsis after rituximab treatment and unspecified sepsis after infliximab treatment). CONCLUSION: The rate of serious AEs, mainly infusion AEs and infections during treatment with infliximab, rituximab, and other GEBAs proved to be relatively low in patients with different RDs. At the same time, the use of biological agents could lower RD activity in the presence of severe visceral injuries refractory to conventional immunosuppressive therapy.

[Signs of hypercoagulation and activation of fibrinolysis in patients with Wegeners's granulomatosis and Schoenlein-Genoch's purpura].

The patients with Wegener's granulomatosis and Schoenlein-Genoch's purpura included in this study were examined in the E.A.M. Tareev Clinic during 2006-2008. They showed signs of hypercoagulation and activation of fibrinolysis, viz. enhanced SFMC, D-dimer and antiphospholipid antibody levels, platelet aggregation. Hypercoagulation correlated with the activity of both Wegeners's granulematosis and Schoenlein-Genoch's purpura.

[Pulmonary lesions in Wegener's granulomatosis].

Pulmonary lesions are the commonest and prognostically unfavourable visceral pathology in Wegener's granulomatosis. The author discusses clinically and reongenologically detectable lesions associated with this systemic vasculitis with special reference to its most severe forms (alveolar bleeding and infectious complications frequently caused by active immunosuppressive therapy). Diagnostic (including early) and modem therapeutic modalities of Wegener's granulomatosis are considered.

[Experience with rituximab treatment (monoclonal antibodies to B-lymphocyte CD20 receptors) of Wegener's granulomatosis patients with renal impairment].

AIM: To assess efficacy of rituximab in patients suffering from Wegener's granulematosis (WG) with renal disease. MATERIAL AND METHODS: We analysed clinical laboratory data from 9 WG patients with renal disease treated with rituximab in E.M. Tareev clinic. RESULTS: The treatment led to a complete remission in 7 (77.8%) patients, a partial remission--in 2 (22.2%) patients. Vasculitis activity regressed including renal damage (a decrease of 24 h proteinurea, enhanced glomerular filtration rate). A prednisolone dose decreased from 38.3 to 10 mg/day (to month 6) and to 7.5 mg/day (to month 12). Non-selective cytostatic drugs were discontinued in all the patients. Recurrences occurred in 3 (33.3%) patients, one with lethal outcome after 6 months of rituximab administration, in two cases one more course of rituximab produced another complete remission. Serious side effects were absent. CONCLUSION: Rituximab demonstrated high efficacy in the treatment of WG with renal affection resistant to standard therapy, in multiple side effects of standard immunosuppressive therapy and recurrent course. Rituximab help overcome steroid dependence even at late stages of the disease.

[Severe Wegener's granulomatosis successfully treated with rituximab].

The paper discusses the problems of the diagnosis and treatment of Wegener's granulomatosis, the most common anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. It describes a clinical case in which the administration of rituximab could achieve remission of severe Wegener's granulomatosis in a young man having numerous adverse reactions associated with the long-term use of high- and average-dose glucocorticoids and nonselective immunosuppressive agents. A place of rituximab in current drug therapy for Wegener's granulomatosis is shown.

[Myocarditis and fibroplastic endocarditis in Wegener's granulomatosis].

The paper describes an autopsy case of Wegener's granulomatosis with a rare variant of a cardiac lesion--the concurrence of aortic valvular disease (aortic regurgitation), fibroplastic endocarditis, and complete transverse blockade, followed by pacemaker implantation. The direct cause of death in the female patient was multiple organ dysfunction: progressive chronic heart failure, adult respiratory distress syndrome, acute hepatorenal failure, and pancreonecrosis. The data available in the Russian and foreign literature on investigations dealing with cardiac pathology in patients with Wegener's granulomatosis are analyzed.

[Churg-Strauss syndrome in patients with cardiac problems].

Clinical observations of patients with Churg-Strauss syndrome and cardiac disorders are reported. In one case, both myocardium and endocardium were affected. Severe cardiac insufficiency was the immediate cause of death in one patient. Another observation revealed a benign variant of the disease associated with exudative pericarditis. A review of domestic and foreign literature concerning cardiac pathology in patients with Churg-Strauss syndrome is presented.

[Involvement of lacrimal organs in Wegener's granulomatosis].

Wegener's granulomatosis (WG) is a primary systemic vasculitis characterized by the development of granulomatous inflammation and necrotizing vasculitis of small- and middle-sized vessels. The clinical symptoms of the involvement of lacrimal organs in WG are of no specificity. Lacrimal tract lesion is encountered in prolonged Wegener's granulomatosis. Whether surgical intervention can and should be made in these patients remains to be debated. Successful surgical treatment for chronic dacryocystitis with recurrent lacrimal sac phlegmon in a female patient with WG has been used as an example to show that endoscopic endonasal dacryocystorhinostomy is the most sparing surgical treatment of dacryocystitis and therefore it is preferable in WG patients and effective at remission during systemic therapy with additional doses of corticosteroids in the pre- and postoperative periods. Lacrimal gland involvement (more commonly diffuse infiltration) is observed at the early stages of the disease and may be the first manifestation of WG so the latter should be excluded when long-term therapy for chronic dacryoadenitis fails.

[Cardiac lesion in the Churg-Strauss syndrome].

The Churg-Strauss syndrome is a systemic vasculitis, the manifestations of which are asthma, eosinophilia, pulmonary infiltrates, poly- and mononeuropathy, polyserositis. Along with nodular polyarteritis and nonspecific aortoarteritis, the Churg-Strauss syndrome belongs to a group of systemic vasculitis, in the clinical picture of which cardiac lesion is recognized as one of the leading visceral manifestations and may be a common cause of fatal outcomes. In the Churg-Strauss syndrome, cardiac pathology may be associated with the involvement of the endocardium, myocardium, and pericardium. The paper describes a case showing the poor course of the disease in a young female patient in whom the heart is involved in a pathological process with the development of severe heart failure, resulting in death. There is a rare concomitance of diffuse myocardial damage, coronary lesion, and valvular pathology - eosinophilic endocarditis. The diagnosis has been verified on the basis of the data of clinical and additional studies and the results of microscopic studies. The data available in the Russian and foreign literature on cardiac pathology in patients with the Churg-Strauss syndrome are analyzed.

[Clinical significance of echocardiography in patients with systemic vasculitis].

The paper reports results of echocardiographic studies of patients with systemic vasculitis treated at E.M. Tareev Clinic during 1991-2006. The major findings include valve pathology, disturbed regional contractility, exudative pericarditis, systolic and diastolic dysfunction. Most patients examined in 2005-2006 turned out to have enhanced left ventricular systolodiastolic (Tei) index.

[Aortal regurgitation and atrioventricular block III in Wegener's granulomatosis].

The article presents a clinical observation of a female patient suffering from Wegener's granulomatosis with a rare variant of cardiac involvement--a combination of an aortal valvular disease (aortal regurgitation) and total atrioventricular blockade--who later underwent pacemaker implantation. The direct cause of the lethal outcome in this patient was destructive pancreatitis. Data from Russian and foreign literature on cardiac pathology in patients with Wegener's granulomatosis are analyzed.

[The peculiarities of renal lesion in nodular polyarteritis].

Analysis of the medical records of 122 patients with nodular polyarteritis showed that the most frequent visceral manifestations were renal (93.4%), cardial (72%), and gastrointestinal (57.4%) ones. Central nervous system (CNS), pulmonary, and peripheral arterial lesions were less frequent (36.8%, 17.2%, and 6.6%, respectively). Renal lesions were manifested by arterial hypertension (AH) in 107 patients, urinary syndrome in 97, nephrotic syndrome in 7, and rapidly progressing glomerulonephritis in 5 patients. Monofactor analysis revealed the following predictors of poor prognosis: malignant AH, nephrotic proteinuria, male sex, body mass reduction, intestinal ulcers, gastrointestinal hemorrhage, CNS lesion, heart failure, and pulmonary lesion. The relative risk of lethal outcome was the highest in nephrotic proteinuria (3.5) and malignant AH (2.9). In 56% of cases death was caused by cardiovascular complications, in 18%--chronic renal failure, in 11%--abdominal complications.

[Cardiac lesion in systemic vasculites: manifestations, diagnosis, and treatment].

The article contains analysis of Russian and foreign literature on cardiac lesions in patients with system vasculites (SV). The frequency of cardiovascular involvement in various SV forms was evaluated. These forms include non-specific aortoarteritis, giant-cell arteritis, nodular polyarteritis, Kawasaki disease, Wegener's granulomatosis, eosinophilic vasculitiis, and granulomatosis. The authors consider the variants of coronary arterial, endocardial, myocardial, and pericardial involvement, as well as the role of arterial hypertension and the clinical features of different SV with cardiac lesions. Modern diagnostic techniques (echoCG, perfusion myocardial scintigraphy, multispiral computed tomography, and coronaroangiography) are covered.

[Clinical aspects of hypereosinophilia syndrome]. / Klinicheskie aspekty sindroma giperéozinofilii.

To assess clinical peculiarities of hypereosinophilia (HEP), determine approaches to treatment and differential diagnosis of the disease, we examined 115 patients in 1969-2002. We made clinical, laboratory and virusological tests with detection of markers of hepatitis B and C viruses, biopsy of the liver (n = 3), on demand echocardiography, indirect immunofluoresence and enzyme immunoassay of the serum for antibodies to neutrophil cytoplasm in some patients. We grouped patients by the presence of Churg-Strauss syndrome (n = 70), an asthmatic variant of nodular polyarteritis (n = 22), hypereosinophilic syndrome (Loffler 11, n = 15) and eosinophilic pulmonary infiltrates (n = 8). Asthmatic nodular polyarteritis was characterized by high arterial hypertension, frequent finding of HBV, aneurysms and infarctions of the viscera. Bronchial asthma and medicines intolerance were absent, though cardiac failure and other cardiac pathology is frequent. Thus, definition of 4 clinical groups of patients with HEP allows a differential approach to the disease treatment and prognosis.

[Clinical and prognostic value of lesions in the gastrointestinal tract in systemic vascular purpura]. / Klinicheskoe i prognosticheskoe znachesnie porazheniia zheludochno-kishechnogo trakta pri sistemnykh sosudistykh pupurakh.

AIM: To evaluate clinical peculiarities and prognostic value of abdominal syndrome in adult patients with systemic vascular purpura (SVP). MATERIAL AND METHODS: Incidence, clinical picture, complications of abdominal syndrome, its relations with principal extraintestinal manifestations of SVP were studied in 125 SVP patients. Absorption and barrier functions of the small intestine, their correlations with clinical activity of the disease were investigated in 32 SVP patients with no clinical signs of intestinal affection. Computer-assisted morphometry of duodenal mucosa biopsies was conducted and the results were compared to those of intestinal permiability and clinical activity of SVP. RESULTS: Negative correlation was found between the occurrence of abdominal syndrome and the patients' age. The gastrointestinal tract suffered more frequently in men. 21% patients had abdominal complications, association of abdominal syndrome with higher frequency of glomerulonephritis. In the absence of abdominal symptoms, the barrier function of the small intestine for protein macromolecules was impaired. This correlated with exacerbations of skin purpura. Increased intestinal permeability and activity of skin purpura correlated with severity of inflammation in the duodenal mucosa. CONCLUSION: Abdominal syndrome in SVP is an unfavourable prognostic factor indicating possible severe complications and high risk of glomerulonephritis. Subclinical intestinal involvement presenting as barrier dysfunction may contribute to aggravation of skin vasculitis.

[Abdominal emergencies in systemic vasculitis]. / Abdominal'nye katastrofy pri sistemnykh vaskulitakh.

Abdominal lesions are characterized in a patient with acute vascular purpura and a patient with polyarteritis. The former patient developed obturation ileus of the small intestine, the latter--necrosis and multiple intestinal and gall bladder perforation with subsequent peritonitis. In both cases the abdominal syndrome was manifestation of the basic disease. Surgical treatment saved life of the patients. Stable remission was achieved after long-term medication.