[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[Systemic vascular purpura: clinical etiological variants]. / Sistemnye sosudistye purpury - kliniko-étiologicheskie varianty.

Systemic vascular purpura (SVP) represents angiites, heterogeneous by etiology and pathogenesis. Their pathogenetic classification does not fully reflect the clinical picture, course, and prognosis. The authors suggest a clinical etiological approach to differential diagnosis of SVP. With this aim in view they examined 82 patients with SVP hospitalized at Clinic of Therapy and Occupational Diseases of I. M. Setchenov Moscow Medical Academy in 1993-1996. Etiologically-associated differences in clinical manifestations of SVP were detected and clinical etiological variants of disease were distinguished. Endotoxemia was found to be often associated with purpura of different etiology, which can be regarded as a stage in the pathogenesis. The data allow creation of a clinical etiological classification of SVP and development of new therapeutic approaches.

[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.

[Microscopic polyarteritis in a patient with hypertension]. / Mikroskopicheskii poliarterit u bol'nogo gipertonicheskoi bolezn'iu.

A case of microscopic polyarteritis in a male aged 45 years having hypertension for 22 years is reported. There were clinical manifestations (hemorrhages, subfebrile temperature, arthralgias and others) and damages in many organs: productive-necrotic alveolitis, capillaritis of various organs, morphological features of hypertension, atherosclerosis, subendocardial myocardial infarction. The leading clinical feature was rapid progression of renal and pulmonary-heart failure.

[Cryoglobulinemic vasculitis]. / Krioglobulinemicheskii vaskulit.

A postmortem case of cryoglobulinemic vasculitis is reported. A 67-year-old male had hemorrhagic component, affection of the kidneys, skin, lungs and gastrointestinal organs. The disease began in 1994 with extreme weakness, headache, fever, skin eruption. Antibodies to B and C hepatitis were found. The condition of the patient worsened since 1997 when renal deficiency reached the degree of uremia. Before the autopsy the diagnosis was: chronic glomerulonephritis with cryoglobulinemia in context of systemic vasculitis with involvement of the skin, gastrointestinal tract, fever syndrome. Pathomorphologically, the patient had proliferative vasculitis with leukoclasia in the skin, chronic mesangiocapillary glomerulonephritis in the kidney, fibrosing alveolitis and vasculitis with affection of small vessels in the lung, chronic hepatitis in the liver. The anatomopathological diagnosis was as follows: cryoglobulinemic vasculitis of the hemorrhagic vasculitis type with involvement of the kidneys, skin, gastrointestinal tract and the lungs. Differential diagnosis with other microscopic vascilitides: main distinctions of cryoglobulinemic vasculitis are immune deposits consisting of cryoglobulins in the wall of small vessels. The most frequent components of cryoglobulins are IgM and IgG. These are main morphological, classifying and differential-diagnostic signs.

[Clinical problems of nonspecific aortic arteritis]. / Nekotorye klinicheskie problemy nespetsificheskogo aortoarteriita]

AIM: The insight into the causes of late diagnosis and analysis of clinical variants of nonspecific aortic arteritis (NSAA) including rare forms--with involvement of the kidneys, intestine, lungs, heart. MATERIALS AND METHODS: Physical, laboratory and immunological tests, angiography, ultrasound dopplerography were employed in examination of 65 NSAA patients observed in 1955-1996. RESULTS: Accurate diagnosis of NSAA is made late (5 years from the first symptoms, on the average) when ischemic damage has become irreversible. The causes of such situation are outlined with special emphasis on NSAA variants running with affection of the lesser circulation vessels, coronary flow, kidneys (nephritis, amyloidosis), intestine (Crohn's disease, nonspecific ulcerative colitis). Men suffer more than women: they develop more frequently myocardial infarctions, thromboembolism. However, their arteries look better. Mechanisms of NSAA onset and progression may be related to defects in vascular endothelium, hyperproduction of antibodies to cardiolipin, antiendothelial antibodies. CONCLUSION: Management of NSAA meets with the problem of late diagnosis which means greater risk of severe vascular complications and deterioration of the prognosis.

[Heart involvement in hypereosinophilia: the restrictive or the dilated type?]. / Porazhenie serdtsa pri giperéozinofilii: restriktivnyi ili dilatatsionnyi tip?

As many as 60 patients with hypereosinophilia of different genesis were examined. 40 of them manifested the clinical (congestive heart failure in 6, tachycardia in 10, cardialgias in 3, murmur in the heart in 13, pericardial murmur in 3) and/or ECG signs (disorders of repolarization in 25, His bundle block in 4, rhythm disorders in 7, pathologic Q waves in 2) of heart injury. In 15 out of the 20 examined, the echocardiography data corresponded to the dilated pattern of heart injury despite the fact that the changes in contractile function of the left ventricle were less appreciable than in 28 patients with dilated cardiomyopathy. In 2 patients who died (one from congestive heart failure and one from anaphylactic shock) the presence of endomyocardial fibrosis with heart dilatation was confirmed on postmortem examination. One female patient with right ventricular failure manifested the characteristic signs of isolated injury to the right ventricle. In 3 patients, the endocardium appeared thickened. None of the cases showed the signs of restrictive heart injury. The data obtained indicate that hypereosinophilia may be one of the etiologic factors of dilated cardiomyopathy.