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Mucoviscidosis — the disease with an autosomal and recessive mode of inheritance caused by a monogenic mutation and which is characterized by defeat of excretory glands in vitals and systems.
Prevalence of a mucoviscidosis varies depending on population. In the majority of the countries of Europe and North America from 1:2000 to 1:4000 newborns get sick with a mucoviscidosis. According to the Medicogenetic Russian Academy of Medical Science scientific center, prevalence of a mucoviscidosis in Russia makes 1:12 000 newborns. Annually in Moscow is born 10, in Russia — 300, in the USA — 2000, in France, England, Germany — from 500 to 800, and in the world — more than 45 000 children sick with a mucoviscidosis.
In Russia still the majority of cases is not diagnosed or the diagnosis is made in late terms of a disease.
Classification of a mucoviscidosis
I. Mucoviscidosis forms
• Mixed (pulmonary and intestinal) with a gastrointestinal tract disease and bronchopulmonary system (75 — 80%).
• Pulmonary (15 — 20%).
• Intestinal (5%).
II. Phase and activity of process
• Remission phase: • activity:
• Aggravation phase.
Etiology and pathogeny of a disease
The mucoviscidosis is caused by MVTP gene mutation (the mukovistsidozny transmembrane regulator of conductivity) which is located in the middle of a long shoulder of the 7th chromosome. Today more than 1000 mutations responsible for development of symptoms of a mucoviscidosis are revealed. Progress in studying of genetics of a mucoviscidosis is important not only in the long term gene therapy, but also a possibility of its primary prevention (the prevention of the birth of the child sick with a mucoviscidosis).
As a result of a gene mutation the secret developed by excretory glands becomes viscous that causes the majority of the processes which are the cornerstone of a disease pathogeny.
Glands of the mucous, covering respiratory tracts, develop a large number of a viscous secret which accumulates in a gleam of bronchial tubes and leads to full obturation of small bronchioles. In these conditions at children with a mucoviscidosis within the first year of life or later, it is frequent against the viral infection reducing efficiency of local mechanisms of antimicrobic protection, in the lower respiratory tracts a large number of various pathogenic and opportunistic microorganisms, most often it gets:
• Staphylococcus aureus;
• Haemophilius influenzae;
• Pseudomonas aeruginosa.
As a result of infection of motionless and viscous slime the purulent inflammation develops. In the conditions of disturbance of mukotsiliarny clearance the obstruction increases that the obstruction — an infection — an inflammation" conducts to an intensification of infectious process and forming of a vicious circle ".
As a rule, first of all the lower respiratory tracts are infected with S. aureus (most often comes to light in a phlegm at patients with a mucoviscidosis of the first years of life), then P. aeruginosa often joins. Identification of P. aeruginosa, S. aureus, etc.> demonstrates 6 months chronic colonization of the lower respiratory tracts these microorganisms. Progressing of the chronic infectious process caused by P. Aeruginosa usually is followed by increase of the symptomatology caused by damage of the lower airways and progressive deterioration in function of lungs. At this P. aeruginosa it can be transformed to mucoid (mucous) forms which become insensitive to action of factors of a host defense and antimicrobic medicines. At chronic colonization of the lower respiratory tracts of P. aeruginosa the full eradikation of the activator is almost impossible.
The bacterial infection caused by H. influenzae often develops against a SARS and can lead at patients with a mucoviscidosis to the expressed respiratory frustration.
Recently Burkholderia cepacia role increased. The course of the infection caused by this microorganism at a mucoviscidosis, variously. Approximately at 1/3 patients frequent aggravations of bronchopulmonary process are noted, the so-called "cepaccia-syndrome" which is characterized by fulminant pneumonia and a septicaemia develops (the forecast at the same time usually bad). At other patients it significantly does not influence the course of a disease. Existence in a phlegm of B. cepacia increases risk of development of the superinfection caused by P. aeruginosa, S. aureus, H. influenzae.
Sometimes as an accidental find other pathogenic microflora — Klebsiella pneumonie, by Esche-richia coli, Serrata marcescens, Stenotrophomonas maltophilia and Proteus spp is sowed., however the role of these microorganisms in a pathogeny of a mucoviscidosis is not finalized.
Aspergillus fumigatus is sowed from a phlegm of patients with a mucoviscidosis quite often. The most clinically significant form of a fungal infection at a mucoviscidosis is an allergic bronchopulmonary aspergillosis, the frequency of its development in patients with a mucoviscidosis varies from 0,6 to 11%. At untimely diagnosis and for lack of adequate treatment proximal bronchiectasias form, fast progressing of bronchopulmonary process with increase of ventilating frustration is noted.
The modern concept of damage of lungs at a mucoviscidosis specifies that a part in damage of pulmonary fabric is played by immune processes. Immunological disturbances considerably increase at long colonization of the lower respiratory tracts of P. aeruginosa. In the course of the reproduction microcolonies of this microorganism produce virulent factors which damage an epithelium of the lower respiratory tracts, stimulate development of mediators of an inflammation, increase permeability of capillaries, cause a leukocytic infiltration.
The pancreas secret condensation often leads to obstruction of its channels till the child's birth. As a result pancreatic enzymes which continue to be produced in an acinus in usual quantity do not reach a duodenum. Accumulation of active enzymes leads to a pancreas tissue autolysis. Often on the first month of life the body of a pancreas represents accumulation of cysts and fibrous fabric (other name of a disease from here — kistofibroz). As a result of destruction of a pancreas processes of digestion and absorption are broken (first of all fats and proteins), deficit of fat-soluble vitamins develops (And, D, E and K). In the absence of the corresponding treatment it leads to a delay of physical development of the child. At some mutations of a gene of a mucoviscidosis injury of a pancreas progresses slowly, and its function remains rather safe for many years.
Can lead disturbances of transport of sodium, chlorine and water in a small bowel at newborns to obstruction of its distal departments dense and viscous meconium — to mekonialny Ilheus. At the same time in some cases the atresia of a small bowel develops. The wall of excessively expanded gut can be broken off till the child's birth, mekonialny peritonitis as a result develops.
Children and adults can also have an acute, subacute or chronic obstruction of distal departments thin and proximal departments of a large intestine a sticky secret mucous and fecal masses, leading to development of intestinal impassability.
Invagination of a small bowel can be other reason of enteric impassability at children with a mucoviscidosis.
Delay of evacuation of contents from a stomach, the raised products of hydrochloric acid, disturbance of a vermicular movement of a stomach often lead to development in patients with a mucoviscidosis of a gastroeozofagealny reflux which development is promoted also by use of some medicines reducing a tone of the lower esophageal sphincter (theophylline, salbutamol), or certain types of physical therapy. Because of recurrent or constant regurgitation of contents of a stomach the esophagitis of varying severity, sometimes with development of a gullet of Barrett develops in a gullet. At a high gastroesophagal reflux aspiration of gastric contents with aspiration damage of lungs is possible.
The secret of sweat glands at patients with a mucoviscidosis is characterized by the increased concentration of sodium and chlorine: content of salt exceeds a normal indicator approximately by 5 times. Such anomaly of function of sweat glands comes to light already at the birth and remains throughout all life of the patient. In the conditions of hot climate excessive loss of salt through integuments leads to electrolytic frustration, a metabolic alkalosis and predisposition to a heatstroke.
The azoospermism at men with a mucoviscidosis is connected with inborn lack, an atrophy or obstruction of a seed cord. The specified anomalies occur also at part of males from among mucoviscidosis gene carriers.
Decrease in fertility at women is caused by increase of viscosity of the separated cervical channel of a uterus that complicates migration of spermatozoa.
Clinical signs and symptoms of an illness
Clinical manifestations of a mucoviscidosis depend on defeat of various bodies and systems and include:
• signs of defeat of bronchopulmonary system;
• signs of damage of a pancreas;
• signs of a gastrointestinal tract disease;
• signs of defeat of gepatobilliarny system;
• sweating disturbance;
• disturbance of reproductive function.
Any of the specified symptoms can be observed at children of younger or advanced age (atypical cases of emergence of a symptom of "drum sticks" and a liver disease in the first years of life are known).
At most of patients the first symptoms of a mucoviscidosis come to light on the first year of life though cases of later are known, up to mature age, development of a disease. The mucoviscidosis symptomatology substantially depends on mutation type (or mutations). The most widespread is the mutation at which clinical signs of a mucoviscidosis appear at early age, insufficiency of a pancreas (90% of cases) develops.
Clinical manifestations of a mucoviscidosis in the neonatal period:
• mekonialny Ilheus (at 20% of newborns with a mucoviscidosis), in some cases the peritonitis connected with perforation of an intestinal wall. To 70 — 80% of children with mekonialny Ilheus are sick with a mucoviscidosis;
• long jaundice which comes to light at 50% of patients with mekonialny Ilheus.
Clinical manifestations of a mucoviscidosis on the first year of life.
The combination of the following symptoms is characteristic of most of the children of chest age suffering from a mucoviscidosis:
• disturbance of a chair;
• lag in physical development.
At the same time one of them can act as the leader.
Cough, at first dry and rare, progresses further to chronic, sharp, frequent and a little productive; fits of coughing can provoke vomiting. In certain cases he reminds cough of patients with whooping cough. Emergence of cough can be connected with an upper respiratory tract infection.
The frequent, plentiful, fetid, oily chair containing the undigested remains of food is characteristic of patients with a mucoviscidosis. Fecal masses is hardly washed away from a pot, diapers, there can be visible impurity of fat.
In certain cases lag in physical development can be the only symptom of a disease.
5% of patients the first clinical manifestation of a mucoviscidosis can have a prolapse of the rectum to which fits of coughing at children with the changed chair, the insufficiency of food weakened by a muscle tone, swelling of intestines and incidental locks contribute.
At careful inspection hurried breathing, increase in the perednezadny size of a thorax and poorly expressed, but permanent retraction of the lower intercostal muscles is found. Auskultativny pathological signs can not come to light or be present at a look dry and wet small at all - and large-bubbling rattles. On the roentgenogram of bodies of a chest cavity reveal consolidation of walls of bronchial tubes, and also various degree consolidation or the increased lightness of pulmonary fabric. Atelectases in segments and shares of lungs can develop, and defeat of the right upper share belongs to diagnostically significant signs of a mucoviscidosis.
Mucoviscidosis manifestation at preschool age — rather unusual occurrence.
For lack of the corresponding treatment the prolapse of the rectum is noted at 25% of patients with a mucoviscidosis, as a rule, at the age of 1 — 2 flying. At children 5 years are more senior this symptom meets much less often.
Only seldom or never the diagnosis of a mucoviscidosis is not established before achievement of school age by patients that can be connected with "soft" mutations and relative "safety" of function of a pancreas.
Mucoviscidosis manifestation cases at teenage and mature age without any symptoms of a disease occur in the anamnesis extremely seldom and are characterized by less typical clinical manifestations.
Symptoms of an aggravation of bronchopulmonary process at patients with a mucoviscidosis:
• change of character of cough;
• emergence of night cough;
• increase in quantity of a phlegm and change of its character;
• increase of an asthma;
• pulse increase;
• deterioration in appetite;
• decrease in body weight;
• decrease in tolerance to an exercise stress;
• deterioration in a physical and X-ray pattern in lungs;
• deterioration in indicators of function of external respiration.
Complications of a mucoviscidosis
The lack of vitamin E is shown by hemolitic anemia at newborns and neurologic symptomatology at children of advanced age.
The obstruction of distal departments of a small bowel occurs at 2% of children 5 years are younger, at 27% of patients 30 years, 7 — 15% of patients of all age are aged more senior.
• abdominal pain;
• the palpated increased caecum;
• partial or full intestinal obstruction to extremely viscous contents of ileocecal department of intestines.
The heavy obstruction is followed by a pain syndrome, intestines swelling, vomiting, a lock and emergence of levels of liquid on the survey roentgenogram of an abdominal cavity.
Such complications as nasal polyposes and a cholelithiasis, often occur at patients with a mucoviscidosis and usually proceed asymptomatically.
Clinical displays of allergic bronchopulmonary aspergillomycosis.
In process of increase in average life expectancy of patients with a mucoviscidosis such late displays and complications of a disease as a diabetes mellitus and heavy hepatic pathology which because of small life expectancy were considered earlier atypical for this disease even more often are registered.
The diabetes mellitus comes to light at 20% of adult patients with a mucoviscidosis. Development of a diabetes mellitus can be provoked by therapy of GKS or high-calorific food. Clinical manifestations are typical for diabetes — thirst, a polyuria, a polydipsia, decrease in body weight. However ketoacidosis at the diabetes mellitus which developed against a mucoviscidosis meets seldom.
The liver fibrosis developing in a varying degree almost at all patients with a mucoviscidosis in 5 — 10% of supervision progresses to a serious illness of a liver with biliary cirrhosis and portal hypertensia.