The Chronic Granulematozny Illness (CGI) represents the syndrome which is characterized by the recurrent bacterial and fungal infections caused by disturbance of bactericidal activity of phagocytes and pathological shifts of an oxidizing metabolism during phagocytosis. The morphology of neutrophils and monocytes does not change, specific humoral and cellular immunity remains normal.
Etiology. Children of both sexes get sick, girls makes about 20% of them. At most of boys inheritance is linked to X-chromosome. For example, intermediate dysfunctions of neutrophils are noted at mothers of patients and their relatives in whom in peripheral blood two kinds of the neutrophils revealed when coloring nitroblue tetrazoliy are found. Female carriers seldom suffer from heavy infections, however at some patients with a chronic granulematozny illness the skin lymphocytic infiltrates similar to that at a diskoidny lupus erythematosus were noted.
At most of sick girls genetic transfer of an illness is not established; it is supposed, however, that it is inherited on autosomal recessively type. On the other hand, results of recently conducted researches by means of a chemiluminescence method for the purpose of measurement of an oxidizing metabolism during phagocytosis give the grounds to consider that at women, as well as at men, transfer of a disease is linked to X-chromosome. At patients with a chronic granulematozny illness of girls essential decrease in chemiluminescence of neutrophils is revealed (less than 2% of level in control group). At mothers of these patients and their relatives during phagocytosis intensity of chemiluminescence is at an intermediate level. At fathers and healthy brothers of patients these indicators always are in norm limits.
For an explanation of a possibility of the transfer of a chronic granulematozny illness to female persons linked to X-chromosome it is possible to use a hypothesis of doctor Mary of Lion1. By means of a histochemical method of recovery nitroblue a tetrazoliya or the autoradiografichesky method based on identification of iodination of bacteria during phagocytosis it is possible to find two different populations of neutrophils in mothers of patients with a chronic granulematozny illness (both boys, and girls). Disturbance of an inactivation of normal X-chromosome can be followed by emergence of numerous population of defective phagocytes and clinical displays of a disease in women.
Some patients on erythrocytes have no antigens of system Kel (Mac-Lauda's phenotype), in similar situations it is extremely difficult to pick up compatible blood for transfusion; at boys Kell antigen is absent also on leukocytes that Kel with the membrane factors activating an oxidizing metabolism of the englobing cells can demonstrate close connection of antigens of system.
Male patients have also no cytochrome inneutrophilic leukocytes which is necessary for electronic transport and recovery of oxygen to superoxide. At female patients cytochrome b is defined that confirms independent nature of anomalies of an oxidizing metabolism at patients with phenotypical similar chronic granulematozny illness, i.e. its heterogeneity.
Pathogeny. Process of an attachment of bacteria and phagocytosis at a chronic granulematozny illness proceed normally, however the microorganisms taken in the course of phagocytosis are not exposed to further destruction. Reproduction of bacteria is suppressed, however they keep ability to survive in a cell, as supports a persistirovaniye of infectious process. Phagocytosis does not cause increase of consumption of oxygen, activity of a geksozomonofosfatny way, chemiluminescence or education of reactive radicals of oxygen in neutrophils and monocytes. When radicals arrive from the absorbed microorganisms producing hydrogen peroxide (streptococci and pneumococci) or as a result of action of the related oxidases neutrophils keep usual ability to destruction of bacteria.
Thus, changes of process of an oxidizing metabolism and development of oxidizing reactive radicals belong to the main disturbances which are the cornerstone of a chronic granulematozny illness during phagocytosis. Normal stimulation of activity of nicotinamide adenine dinucleotide (OVER) and nikotinamidadenin-dinucleotide-phosphate (NADF) happens while at the expense of an attachment of a particle the condition of a plasma membrane of a phagocyte changes that in turn leads to emergence of the electrons necessary for recovery of oxygen with its transfer in the electronic excited state, for example in protoxidic or in a hydrogen peroxide form. At sick NAD and NADF are present at the englobing cells, however in the course of phagocytosis activity of these coenzymes does not increase. In such cells there is in a depression a trigger mechanism of increase of activity of NAD and NADF.
Clinical manifestations. In the first months of life children often have hard proceeding infections. The parts of a body which are constantly contacting to bacteria are subject to infection. In areas around a nose and a mouth the eczematic centers to which the purulent adenitis demanding surgical drainage accompanies are often formed. The gepatosplenomegaliya is almost constant sign; very often in a liver staphylococcal abscesses develop. Quite often osteomyelitis, as a rule, of small, and also long tubular bones joins. In the centers of damage of bones, and also in abscesses of soft tissues often find gram-negative microorganisms, such as Serratia marcescens; therefore for the purpose of the choice of the corresponding antibiotic it is necessary to check sensitivity to it of the activators allocated on mediums.
Infections are provoked by a number of gram-positive and gram-negative bacteria. From gram-positive prevail golden staphylococcus, gram-negative are often provided by types of Serratla marcescens and klebsiyelly. The microorganisms which are not containing a catalase, for example N.'s pneumococcus of influenzae and a streptococcus, seldom cause heavy infections in patients with a chronic granulematozny illness because they produce hydrogen peroxide thanks to what give in to destruction even defective phagocytes.
At a chronic granulematozny illness the pneumonitis often develops. Despite carrying out the corresponding antibacterial therapy, in lungs for a number of weeks infiltrates remain, and residual changes come to light on roentgenograms of a thorax within many months. Golden staphylococcus and gram-negative bacteria belong to typical causative agents of a pneumonitis, however in recent years aspergilla became causative agents of extremely heavy pneumonites.
The Granulematozny centers and obstructive complications can extend to any body. Often there is an obstruction of antral department of a stomach. It is necessary to think of this pathology in all cases if the patient complains of persistent vomiting. The fabric received at a biopsy near abscesses or the inflammatory centers, usually contain accumulations of macrophages in which cytoplasm fatty vacuoles are defined.
Treatment. Continuous antibacterial therapy is necessary for prevention and fight against infectious diseases, the patient with a chronic granulematozny illness. At heavy complications appoint intravenous administration of antifungal drugs and antibiotics.
Transplantation of marrow – the radical, but seldom applied way of treatment of a disease, because of a high probability of infectious diseases.
Gene therapy – introduction to stem cells of marrow of a normal gene of gp91phox. There are data on successful effects of this operation and full treatment from a chronic granulematozny illness. But, unfortunately, the statistics says that such cases are quite rare. Besides there are messages on various complications owing to use of gene therapy. Technologies and knowledge in the field of human genome are constantly improved and there is a hope that in the future gene therapy in treatment of a chronic granulematozny illness will be more successful.
1 Any inactivation of X-chromosome is called process lionizatsy by the name of doctor Mary Lyon who for the first time stated this hypothesis.