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Rendu-Osler-Weber disease or hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disease. It is characterized by vascular dysplasia with the formation of telangiectasias on the skin, mucous membranes of the respiratory and digestive tracts, arteriovenous malformations (AVMs) in the internal organs, which is manifested by bleeding. Diagnosis is based on Curacao criteria: recurrent and spontaneous nosebleeds, multiple telangiectases on the characteristic localizations, AVMs in one or more of the internal organs, a family history of HHT (i.e. first-degree relative who meets these same criteria for definite HHT). Therapy is aimed at preventing and stopping gastrointestinal, nosebleeds, correction of iron deficiency anemia. A promising method of therapy is the use of angiogenesis inhibitors, in particular bevacizumab. The article presents a description of a clinical case of HHT in a 49-year-old woman with telangiectisia on the mucous membrane of the tongue, gastrointestinal tract and liver AVMs.

ErdheimChester disease (ECD) is a rare non-Langerhans histiocytosis with multisystem inflammatory infiltrates consistent of monocytes/macrophages, reactive microenvironment and fibrotic fields. Cardiovascular involvement is one of the most frequent manifestations of ECD that can lead to life threating complications. In this article we are reporting a clinical case of ECD with cardiac involvement in a young patient.

Gaucher disease (GD) is the most common lysosomal storage disorder, resulting from a deficiency in the activity of a lysosomal enzyme glucocerebrosidase, which is involved in the catabolism of sphingolipids. The phenomenal progress in understanding the pathogenesis and development of specific therapy of this disease over the past 60 years dramatically changed the clinical phenotype of GD, turning a severe progressive disorder into an asymptomatic metabolic defect. The evolution of the understanding of GD associated with fundamental discoveries in the field of cell biology, biochemistry and genetics may be of interest to a wide audience as a model of the effective work of the scientific community in the treatment of rare metabolic pathology.

Currently, the main pathogenetic method for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) is the treatment with recombinant monoclonal antibodies that block the C5 component of the complement system. Eculizumab is the first biotechnological drug, which is a monoclonal antibody, with proven clinical efficacy and safety for the treatment of patients with PNH, which is used in world clinical practice. In Russia, in the framework of the state program Development of the pharmaceutical and medical industry for 20132020 was developed Elizaria (JSC GENERIUM) the first biosimilar of the original drug eculizumab., Aim: To evaluate the pharmacokinetic and pharmacodynamic parameters, as well as safety and immunogenicity parameters of the drug Elizara in the induction phase of therapy in previously untreated patients with PNH., Materials and Methods: The study included 11 patients with PNH aged 26 to 75 years who had not previously received eculizumab. Each of the study participants was injected with the studied drug Elizaria at a dose of 600 mg intravenously once a week for 4 weeks., Results: During the clinical study, it was noted that the concentration of the studied drug significantly increased by the time the infusion was completed and then gradually decreased to a minimum at the end of the dosing interval. The average concentration of eculizumab 5 minutes before the administration of the study drug at all visits exceeded 35 g/ml, the minimum concentration sufficient to completely inhibit intravascular hemolysis in patients with PNH. The pharmacodynamic efficacy of the drug Elizaria was confirmed by a decrease in the concentration of the membrane-attack complex (MAC) after the first infusion of the drug was maintained at stable levels until visit 5. A persistent decrease in the level of MAC and a four-fold decrease in the average values of lactate dehydrogenase to visit 5 from 1286.4 to 280.9 U/l demonstrated a marked decrease in activity and stabilization of the hemolytic process against the background of the induction of therapy with Elizaria at a dose of 600 mg once a week and confirmed the effecacy of the study drug. Among the 9 adverse events, only 5 had a relationship with the studied drug, including one serious adverse event in the form of an allergic reaction, which, according to the researcher, had a possible cause-effect relationship with the infusion of the studied drug. In 2 patients, low-titer binding anti-drug antibodies were detected without neutralizing activity during treatment with the studied drug, which may indicate its low immunogenicity., Conclusion: The study evaluated the pharmacokinetic and pharmacodynamic properties of the drug Elizaria in the regimen of induction therapy in previously untreated patients with PNH, confirming its efficacy. The study demonstrated the safety and low immunogenicity of the study drug.

Enzyme replacement therapy (ERT) is the standard for the treatment of Gaucher disease (GD). A lifelong intravenous administration of a recombinant analogue of human glucocerebrosidase compensates for the functional deficiency of its own enzyme. The use of ERT has changed the clinical phenotype of GD, a severe progressive disease has been turned into the status of an asymptomatic metabolic defect. At the same time, a reduced dosing ERT regimen applied in Gaucher patients who had achieved therapeutic goals has not yet been developed.

Differential diagnosis of bone involvement in patients with Gaucher disease can be challenging. Other diseases with similar radiological signs should be ruled out. Here we present a clinical case of tuberculous sacroiliitis in the patient with type I Gaucher disease. Advanced radiological methods of examination are described. Our case report proves the necessity of an individual approach to the management of such cohort of patients. Keywords: Gaucher disease, tuberculosis of bones and joints, differential diagnosis, comprehensive treatment.

Gaucher disease is the most common form of hereditary enzymopathies combined into a group of lysosomal storage diseases. The basis for the disease is a hereditary deficiency of the activity of acid β-glucosidase, a lysosomal enzyme involved in the catabolism of lipids, which results in the accumulation of nonutilized cellular metabolism products in the macrophage lysosomes. The main clinical manifestations of type 1 Gaucher disease are cytopenia, hepatomegaly, and splenomegaly, and bone lesion. One of the atypical clinical manifestations of Gaucher disease is damage to the lungs with the development of pulmonary hypertension, which is usually considered within the underlying disease - the development of pneumosclerosis due to macrophage dysfunction. The paper describes a case of progressive pulmonary hypertension in a patient with type 1 Gaucher disease.

Gaucher disease (GD) is an inherited enzymatic defect resulting from a deficiency of acid [3-glucosidase, a lysosomal enzyme involved in the degradation of cell metabolic products. The major clinical manifestations of GD are hepatosplenomegaly, cytopenia, and bony involvement varying from asymptomatic osteopenia to severest osteoporosis and ischemic necrosis to develop irreversible orthopedic defects. Timely enzyme replacement therapy with recombinant glucosidase makes it possible to arrest disease progression and to prevent damage to the vital organs. However, GD in adult patients is frequently diagnosed in the presence of occurring osteoarticular lesions (arthrosis deformans, abnormal fractures). In these instances, besides enzyme replacement therapy, high-quality orthopedic care is required. The description of the case history of a patient undergoing splenectomy in childhood is given as a clinical example of severe osteoarticular lesion in GD and complex differential diagnosis with the intercurrent disease extrapulmonary tuberculosis.

Aim: To characterize the genotype and genotype-phenotype correlations in patients with Gaucher disease (GD) in the Russian Federation., Materials and Methods: One hundred adult patients with GD type 1 were examined. Their clinical study encompassed the evaluation of the severity of osteoarticular lesions from instrumental findings. An allele-specific real-time polymerase chain reaction assay was used to screen four most common acid beta-glucoside gene (GBA) mutations (N370S, 84GG, L444P, IVS2+1)., Results: The N370S mutation and the N370S/? genotype where the second allele was presented with the mutation outside the 4 most common GBA gene mutations were found in the Russian patients with GD. Analysis of the clinical manifestations of the disease revealed no association between the genotype under examination and the severity of osteoarticular lesions and supported the unfavorable role of splenectomy (SE) in the development of severe bony disease., Conclusion: SE should be carried out in patients with unclear cytopenia and splenomegaly after the diagnosis of GD is excluded. The GD patients undergoing SE should receive emergency enzyme replacement therapy to prevent severe osteoarticular lesions and an irreversible orthopedic defect.

Aim: To define an optimal diagnostic and therapeutic algorithm when the acute abdominal syndrome occurs in hematological patients., Materials and Methods: The results of 145 emergency surgeries made in 2006-2008 for acute abdominal syndrome were studied in patients with blood system diseases., Results: Clinical manifestations of acute abdominal syndrome emerge in 1-1.4% of all the patients treated at the Hematology Research Center, Russian Academy of Medical Sciences. There is a need for surgery in 0.5-0.7% of all the patients admitted. In this group of patients, annual postoperative mortality is 12-16%., Conclusion: The routine algorithm for a diagnostic search in hematological patients with acute abdominal syndrome can lead to both hyperdiagnosis and unwarranted surgery, and incorrect choice of expectant policy as well.

The article demonstrates objective difficulties and subjective mistakes in assessment of a clinical picture in a patient with subleukemic myelosis and thrombosis of the portal system. A careful examination of such patients is necessary to reveal latent disorders (in this case--a complete selective IgA deficiency) influencing treatment policy.

Aim: To characterize clinical, diagnostic and therapeutic syndromes of copper overloading in patients with hepatic lesion in combination with hemopoietic disorder., Material and Methods: Treatment results and diagnostic findings are presented for patients with clinical picture of liver cirrhosis, cytopenia and copper overloading. The examination included standard clinical and specific tests, morphological investigation of the bone marrow, copper metabolism in dynamics., Results: A case of a patient is reported in whom Wilson's disease presented in debut with a picture of decompensated liver cirrhosis and immune thrombocytopania complicated by recurrent hemorrhagic syndrome. D-penicillomine treatment initiated ex juvantibus allowed verification of the diagnosis of Wilson's disease and achievement of marked clinical response. In another case laboratory signs of copper overloading were revealed in a patient with liver cirrhosis of viral etiology (HBsAg+) and deep cytopenia associated with uneffective hemopoiesis. Chelator therapy with D-penicillamine regressed cytopenic syndrome and improved functional capacity of the liver., Conclusion: Primary or secondary nature of copper overloading in patients with hepatic cirrhosis and critical cytopenia, pathogenesis of cytopenic syndrome, practical significance of copper hemochromatoses diagnosis are discussed.

Aim: To study changes in serum levels of interleukine-1 beta (IL-1b), IL-6, TNF-alpha (TNFa), HM-HMF and TFR-1 beta (TFR-1b), expression of surface antigens CD14 and CD95 on blood monocytes from patients with chronic hepatitis C (CHC) treated with interferon-alpha (INFa)., Material and Methods: Examinations covered 25 CHC patients and 25 healthy controls. Concentrations of proinflammatory cytokines and growth factors in blood serum were measured with ELISA (kits by "R&D systems", USA). CD14 and CD95 antigen expression on monocytes of venous blood were studied using flow cytoflowmeter (Partes, USA) before and after a 12-week course of INFa., Results: Before INFa treatment CHC patients had significantly elevated serum concentrations of TNFa, HM-KSF and TFR-1b. Coexpression of antigens CD14+ and CD95+ was found on 61% of blood monocytes. Three-month INFa treatment lowered levels of TNFa, GM-KSF and CD95+ expression on monocytes as well as TFR-1b concentration in the serum which correlated with a positive trend in the standard clinicolaboratory and virusological indices in the examinees., Conclusion: Changes in serum indices of proinflammatory cytokines and growth factors, in expression of CD95 on blood monocytes from CHC patients treated with INFa show an important role of cytokines system activation and mechanisms of programmed cell death in pathogenesis of chronic HCV infection.

Aim: To examine hemopoiesis and to estimate proinflammatory cytokines in blood serum from 42 patients with chronic viral hepatitis (CVH) associated with 1-3 lineage cytopenia in the blood., Material and Methods: 42 patients with diagnostically complicated hematological picture suggestive of hemoblastosis were examined using standard tests, bone marrow puncture and trepanobiopsy, laparoscopy with biopsy of the liver and spleen, transcutaneous puncture biopsy of the liver under ultrasonic control, explorative laparotomy with splenectomy and liver biopsy and, on demand, laboratory tests for hemolysis, presence of antithrombocytic and antileukocytic antibodies, iron metabolism, karyological analysis of bone marrow cells was also made., Results: The majority of the patients were diagnosed to have chronic hepatitis C with low activity of hepatic inflammation and frequent (55%) absence of the diagnostic antibodies to hepatitis C virus in the serum. In 86% of cases blood cytopenia reflected uneffective hemopoiesis and in 14% of cases hemopoiesis hypoplasia was found., Conclusion: Uneffective hemopoiesis, high content of immune response cells-effectors in the bone marrow and high concentration of TNF in the serum indirectly evidence for a pathogenetic relationship of chronic HCV infection with cytopenic hematological syndromes.

Fever is an important component of immune response of the organism to various stimulating effects (trauma, infection, inflammation). This complex process comprises activation of monocytes/ macrophages, their synthesis and secretion of proinflammatory cytokines and realization of multiple biological effects of cytokines including growth stimulation and differentiation of hemopoietic cells. Recently, there has appeared a trend to growing number of cases with uncommon hyperthermia and 2-3 germ cytopenia in the blood. Activation of the macrophage system and hyperproduction of proinflammatory cytokines can be viewed not only as an essential mechanism of hemopoiesis stimulation but also as a potential cause of hemodepression. The paper analyzes the relations between high functional activity of the macrophage system and development of cytopenia in patients with persistent fever. Functional activity of the macrophage system was studied on the model of patients with tumors or reactive proliferations of monocytes-macrophages as the latter are the main sources of IL-1-cytokine--a mediator of human fever. To prove the suggested correlation and its significance, a correlation analysis was made of 29 clinical and laboratory parameters in 184 patients and 100 controls.

Standard (hemogram, routine biochemical indices) and non-standard hematological parameters reflecting monocytic-macrophagal system (MMS) function and antioxidant defense were investigated in 140 subjects who had worked in radionuclide-contaminated zone after the Chernobyl accident. As shown by measurements of iron serum metabolism, lysozyme, total interferon, CIC, chemiluminescence of venous blood mononuclear leukocytes, MMS in 50% of them underwent negative changes in suppressed antioxidant defense. Standard hematological findings registered abnormalities only in 8-27% of the examinees.

Morphological and cytochemical examinations of mononuclear phagocytes (MP) from venous blood leukoconcentrate were carried out in 25 patients with chronic monocytic leukemia, 7 patients with malignant histiocytosis, 3 patients with Langerhans' cell histiocytosis and 26 patients with reactive proliferations of the cells belonging to MP system associated with autoaggressive, infectious diseases or tumors. Morphofunctional features of MP from the patients with tumor and reactive histiocytosis may serve additional criteria in differential diagnosis of the diseases in which pathological process runs with participation of MP system cells.

Langerhans cell histiocytosis (LCH) and histiocytosis class II (without Langerhans cells) were treated in 10 and 2 patients, respectively, with alpha-interferon preparations: recombinant alpha 2-interferon and two combined preparations containing natural alpha-interferon and immune response phase 1 cytokines. The patients' age ranged from 18 to 61 years, all of them had multiple lesions. Six of them exhibited dysfunctions of the affected organs. As shown by the results of 16-52-month follow-up, LCH patients' disease persisted in chronic active stage without progression (8 cases) or reached a complete remission (1 case), one patient died. In histiocytosis class II alpha-interferon administration was uneffective.

The authors have summarized the research data on lymphoid cells of the lymph nodes and peripheral blood of normal donors, patients with hematological nonlymphoproliferative diseases, reactive lymphadenopathies and malignant lymphoproliferative diseases (Hodgkin's disease, chronic lympholeukemia and lymphosarcomas). The data indicate that the use of the panel of the simplest tests of immunological phenotyping provides in many cases sufficient information for differential diagnosis of reactive lymphadenopathies and malignant lymphoproliferative diseases as well as for diagnosing the early stage of lymphosarcoma leukemization.