Character features Charge syndrome. Primary system and pulmonary vasculites Treatment of Charge Strauss Syndrome

Charge-Stross syndrome - eosinophilic granulomatous inflammation, characterized by systemic necrotic segmental panagitis of small vessels (arterioles and veul) with eosinophilic perivascular infiltration. Changes in vessels and organs lead to the formation of numerous eosinophilic infiltrates in tissues and organs (especially in pulmonary tissue), followed by the formation of perivascular granuloma.

Epidemiology

A rather rare disease, its share accounts for only the fifth part among all the vasculites of the group of nodule polyarteritis. It is more common in middle-aged people, but cases of disease in children and older persons are registered.

Symptoms of Charge Strauss Syndrome

The initial signs of the disease are characterized by inflammatory allergic reactions: rhinitis, asthma. It is later developing eosinophilia, eosinophilic pneumonia ("volatile" eosinophilic pulmonary infiltrates, heavy bronchilistic syndrome), eosinophilic gastroenteritis. In the expanded stage, the clinical manifestations of the systemic vasculitis are dominated: peripheral mono- and polyneurite, various skin rashes, lesion of the gastrointestinal tract (abdominal pain, nausea, vomiting, diarrhea, less often bleeding, perforation, eosinophilic ascites). The defeat of the joints can manifest themselves with arthritis or arthritis similar to that of a nodule polyarteritis. The kidney damage occurs quite rarely and proceeds benign, but it is possible to develop focal jade, leading to AG.

The pathology of the heart is found more than half of the patients and is the most common cause of death. The spectrum of the lesion is the most diverse - most often diagnosed coronaryitis, often complicating myocardial infarction, as well as myocarditis (10-15%), DCMP (14.3%), which is pericarditis, tensile fibroplastic endocarditis (characterized by fibrosis of endocardium, damage to papillary muscles and chord , insufficiency of mitral and triple valves, the formation of cloth thrombus with subsequent thromboembolic complications). In 20-30% of patients develop stagnant heart failure. The addition of infectious endocarditis is possible.

Diagnosis of Charge Strauss Syndrome

The characteristic laboratory indicator of the Charge-Strauss syndrome is the peripheral blood hyper rouosinyl (\u003e 10 9 l), but its absence is not a reason for eliminating this diagnosis. A correlation is established between the level of eosinophilia and the severity of the symptoms of the disease.

Other laboratory indicators are normal normal normocitar anemia, leukocytosis, an increase in EC and the concentration of C-reactive protein (CRH). A typical change is to increase serum levels, Ans, especially reacting with myeloperoxidase, in contrast to ANS characteristic of vegetable granulomatosis.

For the diagnosis of heart lesions, highly efficient Ehocheg.

Classification Criteria of Charge Strauss Syndrome (MSI A. ET Al., 1990)

• Asthma - difficulty breathing or diffusers in exhalation.
• Eosinophilia is the content of eosinophils\u003e 10% of all leukocytes.
• Anamnesis allergy is an adverse allergic history in the form of polysis, allergic rhinitis and other allergic reactions, with the exception of drug intolerance.
• Mononeiropathy, multiple mononeyropathy or polyneeropathy by the type of "gloves" or "stocking".
• Pulmonary infiltrates - migratory or transient pulmonary infiltrates diagnosed with x-ray examination.
• Sinusites - pain in the spicy sinuses or radiographic changes.
• Summary eosinophils - the accumulation of eosinophils in the outcasting space (according to biopsy).

The presence of patient 4 and more criteria allows you to diagnose "Charge-Stross syndrome" (sensitivity - 85%, specificity - 99%).

The differential diagnosis is carried out with a nodule polychater (asthma and atypical lesion of the lungs), vegetable granulomatosis, chronic eosinophilic pneumonia and idiopathic hyperoeosinophilic syndrome. For idiopathic hyperoosinophilic syndrome, a higher level of eosinophils is characterized, the lack of bronchial asthma, allergic, the thickening of the endocardium is more than 5 mm with the development of restrictive cardiomyopathy, resistance to the treatment of GLCLCorticoids. In the vegetable granulomatosis, necrotic changes in the ENT organs are combined with minimal eosinophilia and frequent kidney damage; Allergies and bronchial asthma are found, in contrast to Charge-Strauss syndrome, no more than in the population.

Treatment of Charge Strauss Syndrome

The basis of treatment is glucocorticoids. Prednisolone is prescribed at a dose of 40-60 mg / day, the abolition of the drug is possible not earlier than one year after the start of treatment. In case of insufficient treatment of prednisolone, cytostatics - cyclophosphamide, azathioprine, use cycloofosphamide, or by severe fast-horror flow.

Prevention

Due to the fact that the etiology of vasculitis is unknown, the primary prophylaxis is not carried out.

Forecast Charge Strauss Syndrome

The forecast of Charge-Strauss syndrome depends on the degree of respiratory failure, the nature of cardiac disorders, activity and generalization of vasculitis; With adequate therapy, 5-year survival rate is 80%.

Charge syndrome is a rare disease that occurs during the early development of the fetus and affecting several organ systems.

Abbreviation comes from the first letter of the most common features observed in these children:

• (C) \u003d Koloboma (usually retinohoroidal) and defects of cranial nerves (80-90%);
• (H) \u003d heart defects (50-60%);
• (R) \u003d growth slowdown, development (70-80%);
• (G) \u003d insufficient development of the genital organs due to hypogonadotropic hypogonadism;
• (E) \u003d anomalies, sensory hearing loss (\u003e 90%).

Diagnostics is based on a specific set of features. In addition to the peculiarities, most children with Charge syndrome have characteristic facial features:

• asymmetric facial nerve paralysis;
• cleft lip or sky;
• the atresia of the esophagus (blindfall);
• tracheostophageal fistula.

Symptoms vary from one child to another. The reason is usually a new mutation of the CHD7 gene, or rarely, changes in the area of \u200b\u200bchromosome 8Q12.2, where CHD7 is located.

Postnatal growth decline, problems with swallowing are very often associated with dysfunctions of cranial nerves. Three-dimensional reconstructions of MRI scanning showed impaired temporal bone from more than 85% of victims.

Synonyms

• Charge Association;
• Hall-Hitnener syndrome;
• Koloboma, Atresia Hoang, slowdown in growth, development, abnormalities of sexual and urinary tract, Ear anomalies.

Charge syndrome affects several organ systems, which leads to multiple birth problems. Other characteristics may not manifest.

The diagnosis should be made by a medical genetic basis on the basis of the presence of at least one major and several minor or random criteria.

Main diagnostic criteria (4 C):

Coloboma is the inability to close the eyeball during the development of the fetus. It can lead to the formation of pupil in the shape of a barrel (Rainbow Koloboma), retinal anomalies, macula or optic nerve.

Very small eyes (microftralmia), missing eyes (anofthalmia) can be heavy forms of pathology. The retinal or optic nerve colobum leads to significant loss of vision, including blind spots, problems with the perception of depth or legal blindness. It is most often found in the retina and is present in 70-90% of patients with Charge syndrome.

Bilateral major retinochoroidal colobromas are a typical ophthalmic feature for people with confirmed CHD7 mutations. However, even eyes with large colobomates can form maculas.

Many children, having a simply rainbow bangs are sensitive to bright light (light-free). Surgery cannot correct the problem. At myopia or hyperopia, glasses help. Sunglasses and a hat with a protective visor save from photophobia.

Anomalies of the cranial nerves

Sensignical (nervous) hearing loss due to deviations in the cranial nerve VIII. Cranial CT often detects hypoplastic snail (81%) with missing semicircular channels.

The loss of hearing and accuracy with the balance is the most common features associated with cochlear hypoplasia, missing semicircular channels.

Charge syndrome is associated with a characteristic view of the ears that appear.

Hearing loss varies from easy to deep deafness. The problems of hearing are very difficult to recognize in young children. Many children receive cochlear implants with sensucleon deafness. Most have problems with balance (vestibular anomalies) associated with missing semicircular channels, which is a key indicator when diagnosing formulation.

Most children with Charges syndrome have problems with swallowing (cranial nerves ix / x). They include the inability to coordinate sucking and swallowing, leading to swallowing and aspiration of food into the lungs (can cause pneumonia).

Many need feeding through a gastrostomy tube (directly in the stomach through the abdominal wall) until they learn to swallow.

Many have an asymmetric face paralysis, one side of the face (cranopy brain nerve VII) is affected. This leads to a lack of expression on the face, which is important when the child works with teachers or therapists.

There is a reduced smell (cranial nerve i), which complicates the study, normal nutrition. Most patients with Charge syndrome have absent or abnormal omeling bulbs on MRI, which indicates a reduced sense of smell.

Research on the smell can predict the presence of hypogonadotropic hypogonadism. The combination of defective smell (anosmia, hyposhythmia) with hypogonadotropic hypogonadism (called) leads to small external genitals. It is very common in Charge and requires consultation with an endocrinologist.

Changal Atresia.

Choanae is a place from the back of the nose to the throat, which allows you to breathe through the nose. Approximately half of all children with disorder these passes are blocked (atresia) or narrowed (stenosis). Surgery can fix these disadvantages.

Patients with one-sided atresia are usually adjusted by 1 surgical procedure at a later age (from 6 months to 18 years). With a bilateral form you need help 2 interventions at an early age (range of 6 days-6 years).

If both sides are affected, it is necessary to take immediate measures to ensure that the newborn can breathe properly and prevent respiratory failure.

An ear

In children with Charge syndrome, unusual ears. A typical ear has a short, wide with a small or missing mour. Spiral (outer fold) can suddenly end in the middle. Center (Concha) often triangular shape. The ears are flexible, sticking out due to weak cartilage.

CHARGE and KABUKI are the result of the loss of functional mutations of the DNA-binding protein chromodomomomine Helicase 7 ( CHD7) and 2D methyltransferase (k) (k) ( KMT2D.), respectively. Although two syndrome are clinically different, there is a significant phenotypic overlap.

Epidemiology of retinoic acid

A very rare disease caused by the exposure to the fetus for retinuous acid (or isototonin, which is used to treat acne) during pregnancy. Ear variables are similar, but other functions are different.

Diagnostics

The doctor conducts a physical inspection on the main and secondary signs of the disorder listed above. Other similar violations must be excluded, such as:

• deletion syndrome 22q11.2;
• mova -vilson's disorder;
• kabuki syndrome;
• callman syndrome;
• haplointensity EFTUD2 (multiple congenital anomalies, mental inferiority characterized by the Mandibulofacial Dysotosis Association with Ear, Hearing, Cleaner Sky, Atresia Chonala, Microcephalus, Mental Disability, Food Atresia, Congenital Heart Vices, Defects of radiation rays).

CHD7 and KMT2D function on the same chromatin modification mechanisms, which gives an explanation of the phenotypic overlap between Kabuki and Charge syndromes.

Molecular genetic testing is available for CHD7 mutations. If the analysis is negative, it is necessary to carry out SNP, since the submicroscopic change of chromosome 8q12.2 occurs sometimes. When both tests are negative, it is necessary to carry out a genome section, since other errors have similar clinical features.

Treatment

Although these children have many problems, they can survive and become healthy, happy citizens. Structural anomalies (chelate atresia, heart defects, lip cleaners) are adjusted surgically.

Problems with feeding and speech shortages require many years of therapy and other interventions. Doctors who are watching victims: genetics, cardiologists, audiologists, ENT, ophthalmologists, urologists, endocrinologists.

More than 50% is experiencing sleep disorders, obstructive apnea in a dream. All the usual treatment methods of obstructive apnea reduce the symptoms.

Recognition of abnormal venous structures during the omnantic surgery is crucial to prevent potentially catastrophic bleeding.

Due to the consequences of the shortage of a cochlear nervous system in making decisions about the treatment of cochlear implantation of the MRI-Eighth nerve estimation should be considered in patients with severe sensucleus hearing loss.

For patients with severe abnormal anatomy of the middle ear, the operation using CT image is useful. This children recommended a bilingual approach to early learning using the sign language and verbal to ensure the best language results. Cochlear implantation gives

Regular doses of growth hormone (GH) have a positive effect on its short-term speed without any problems. Hormonal therapy helps to treat symptoms of hypogonadism.

Professionals participating in treatment include defectologists, professional therapy, physiotherapy, speech therapy. Methods of assistance and educational programs must take into account any violation of perception. Intellect of children with Charge is often underestimated due to the common problems of hearing and vision.

Genetic advice requires victims and their families. Other treatment is symptomatic and supportive. For these complex children, a multidisciplinary medical approach is needed.

Features of development, forecast

Most young children with CHARJ syndrome have delays in psychophysical development. This is primarily due to sensory deficit, frequent diseases, hospitalizations.

Many will catch up with peers in a later child, showing normal intellectual abilities. It is impossible to predict possible development. Early Survival Intervention is important to eliminate sensory deficit, prevent behavioral problems.

Regardless of the degree of internal anomalies of the ear and intellectual abilities, as they can arise, the difficulties of behavior may arise.

- inflammatory-allergic damage to small and medium vessels (capillaries, veins, arterioles), which flows with the formation of necrotizing eosinophilic granulomes. For singer-stroke syndrome, hyperoeosinophilia, the defeat of the broncho-pulmonary system, heart, gearbox, central and peripheral nervous system, leather and joints. The diagnosis of singer-Strauss syndrome is based on the data of the anamnesis, the clinical picture, laboratory studies, radiography of the chest organs, the lung biopsy. As the main therapy, the singer-Strauss syndrome is shown the purpose of systemic glucocorticosteroids and cytostatics.

General

Child-Strauss syndrome is a type of systemic vasculitis with granulomatous inflammation of medium and fine caliber vessels and preferably damage to the respiratory tract. Sundray-Strauss syndrome belongs to polysisystem disorders, most often affecting organs with rich blood supply - skin, lungs, heart, nervous system, gastrointestinal tract. Sonder-Strauss syndrome is largely reminiscent of the nodule periateritis, but unlike it is striking not only small and medium artery, but also capillaries, veins and venules; It is characterized by eosinophilia and granulomatous inflammation, preferably lung damage. In rheumatology, the Sonder-Strauss syndrome occurs rarely, the annual incidence is 0.42 cases per 100 thousand population. People from 15 to 70 years old suffereled syndrome, the middle age of patients is 40-50 years; In women, the disease is detected somewhat more often than in men.

The reasons

The reasons for singer-Strauss syndrome are unknown. Pathogenesis is associated with immune inflammation, proliferative-destructive changes and an increase in the permeability of the vascular wall, thrombosis, hemorrhages and ischemia in the zone of damage to vessels. An excellent titer of antinerophilic cytoplasmic antibodies (ANCA), antigenic targets of which are neutrophil enzymes (mainly proteinase-3 and myeloperoxidase) plays an important role in the development of the singer-Strauss syndrome. ANCA causes premature degranulation and violation of transgeneous migration of activated granulocytes. Vascular changes lead to the emergence of numerous eosinophilic infiltrates in tissues and organs with the formation of obscure inflammatory granulomes.

The defeat of the lungs comes to the fore with the singer-stroke syndrome. In histological examination, interstitial and perivascular eosinophilic infiltrates are detected in the walls of pulmonary capillaries, bronchi, bronchioles and alveoli, perivazal and perilimphhatic tissues. Infiltrates have a variety of shape, usually localized in several lung segments, but they can spread to all pulmonary stake. In addition to acutely inflammatory reactions, scar scarotic changes in vessels and pulmonary fabric are noted.

Provice the development of singer-Strauss syndrome can viral or bacterial infection (for example, hepatitis B, staphylococcal hopes), vaccination, organism sensitization (allergic diseases, drug intolerance), stress, cooling, insolation, pregnancy and childbirth.

Symptoms

In its development, three stages take place in its development syndrome.

Promotional Stage May last several years. In the typical flow, the singer-Strauss syndrome begins with the defeat of the respiratory tract. Allergic rhinitis, nasal obstruction symptoms, polypose growth of the nasal mucosa, recurrent sinusitis, protracted bronchitis with an asthma component, bronchial asthma are appear.

Second stage Sundray-Strauss syndrome is characterized by an increase in the level of eosinophils in peripheral blood and tissues; It is manifested by heavy forms of bronchial asthma with strong bumps of cough and expiratory choking, hemoplange. The attacks of bronchospasm are accompanied by severe weakness, long fever, Malgia, weighty. Chronic eosinophilic lung infiltration can lead to the development of bronchiectatic disease, eosinophilic pneumonia, eosinophilic pleuritis. With the appearance of pleural effusion, pain in the chest during breathing, the increase in shortness of breath is noted.

Third stage Child-Strauss syndrome is characterized by the development and dominance of signs of systemic vasculitis with a polyorgan lesion. In generalizing the chord-Strauss syndrome, the severity of bronchial asthma decreases. The period between the appearance of symptoms of bronchial asthma and vasculitis is an average of 2-3 years (the shorter the gap, the unfavorable disease forecast). There is high eosinophilia (35-85%). From the side of the cardiovascular system, the development of myocarditis, coronary, constrictive pericarditis, insufficiency of mitral and three-rolled valves, myocardial infarction, an entry fibroplastic endocarditis of Lefball has been possible. The damage to the coronary vessels can cause a sudden death of patients with soda-stars syndrome.

For damage to the nervous system, peripheral neuropathy (mononereropathy, distal polyneuropathy "on the type of gloves or stockings" are characteristic; radiculopathy, neuropathy of the optic nerve), the pathology of the CNS (hemorrhagic stroke, epileptic attacks, emotional disorders). From the head of the gastrointestinal tract, the development of eosinophilic gastroenteritis (abdominal pain, nausea, vomiting, diarrhea), less often bleeding, perforation of the stomach or intestines, peritonitis, intestinal obstruction.

In the syndrome of the Black-Strauss syndrome, a polymorphic lesion of the skin appears in the form of a painful hemorrhagic purple on the lower extremities, subcutaneous nodules, erythema, urticaria and necrotic bubbles. Polyartralgia and impassive migratory arthritis are often observed. The defeat of the kidneys is rare, is unbearable, proceeds in the form of segmental glomerulonephritis and is not accompanied by CPN.

Diagnostics

Sick-stroke syndrome patients for primary help usually turn to various specialists - a otolaryngologist, a pulmonologist, an allergist, a neurologist, a cardiologist, a gastroenterologist and late to rheumatologists. The diagnosis of singer-stars syndrome is based on clinical and laboratory data and instrumental research results. The diagnostic criteria of the singer-Strauss syndrome are: hypeozinophilia (\u003e 10% of the total leukocyte), bronchial asthma, mono- or polyneuropathy, sinusitis, eosinophilic infiltrates in the lungs, extravascular necrotizing granulomas. The presence of at least 4 criteria confirms the diagnosis of 85% of cases.

In the singer-stroke syndrome, anemia, leukocytosis, an increase in ESP and the level of general IgE are also revealed. For more than half of the cases of singer-stroke syndrome, the detection of perinuclear antibodies with anti-lifter oxidase activity (RANCA) is characteristic.

Radiography of the chest organs during soda-stars syndrome allows you to detect quickly disappearing, bounded dimensions and focal shadows in the lungs, the presence of pleural effusion. In the biopsy of the lung, the granulomatous inflammation of small vessels, infiltrates in the near-sized space containing eosinophils are determined. The differential diagnosis of singer-stars syndrome should be carried out with a noduler granulomatosis, chronic eosinophilic pneumonia, idiopathic hyperoeosinophilic syndrome, microscopic polyangeitis.

Treatment of singer-Strauss syndrome

Treatment implies a long appointment of high doses of systemic glucocorticosteroids. As the condition improves the dose of drugs reduce. In the presence of lesions of the cardiovascular system, lungs, multiple mononeurite, the use of pulse therapy with methylprednisolone is possible. With the ineffectiveness of glucocorticosteroids, cytostatics (cyclophosphamide, azatioprine, chlorubutin) are used, which contribute to more quick remission and reduce the risk of relapses, but create a high risk of infectious complications. Before starting therapy, all drugs are canceled, to which the patient detected sensitization.

Forecast

Without treatment, the forecast of the singer-Strauss syndrome is unfavorable. In case of polyorgan destruction, the progression of singer-stroke syndrome with a high risk of death from cardiovascular disorders occurs. With adequate treatment, 5-year survival rate is 60-80%.

Citation:Chuchalin A.G. Primary system and pulmonary vasculites // RMW. 2001. №21. P. 912.

Pulmonology Research Institute of RF

Pulmonology Research Institute of RF

FROM The announcement conference on the nomenclature of systemic vasculitis took place in 1992 in Chapel Hill (USA) and played a big role in reaching consensus on classification, diagnostic criteria and methods of treatment of primary vasculitis. Experts from Europe and America discussed histopathological and immunological features of primary systemic vasculites, comparing them with the diversity of clinical manifestations. In the Russian-language medical literature, this topic was discussed by E.M. Tareyev and his students. In recent years, it was considered in the monograph E.L. Nonovova et al. (1999).

In this paper, there is an analysis of modern literary and own clinical data on the issue of pulmonary vasculites, in which small vessels are involved in the inflammatory process. In a special group of vasculitis, according to the nomenclature of rheumatic diseases, microscopic polyangiite, venener granulosis and Chard Strauss syndrome are isolated. In the detailed form, the classification was considered and proposed to a wide practical application of the American society of rheumatologists (1994).

Rackern and Greene (1939) for the first time reported that they observed patients with a special form of a nodule polyarteritis, which was characterized by the attacks of bronchial asthma and a high content of eosinophils. The heavily of bronchial asthma was heavy, which allowed the authors to allocate a certain clinical option of the disease, indicating its unfavorable forecast. In 1951, J. Churg and L. Strauss were included in the heading of a nodule polycharity patients with bronchial asthma, eosinophilia and systemic vasculitis (Charge-Stross syndrome). They described the main anatomical changes that were manifested by the alteration of the vascular wall and extravascular systemic changes. Special attention to the description of systemic tissue damage was paid to necrosis of the vessel wall, eosinophilic exudate, fibrinoidal changes in collagen and proliferation of epitheliodic and giant cells to form granuloma. These anatomical and histological characteristics of the pathological process allowed the authors to allocate a special group of systemic diseases, which they designated as an allergic granuloma, emphasizing these terms the two most characteristic features of the systemic disease: eosinophilia and granulomatous process.

A lot of attempts were made to give a characteristic and classify systemic vasculites. So, Liebow described a group of patients with pulmonary vasculitis and granulomatosis. Morphological changes in the pulmonary fabric are diverse, but still the central place is occupied by vascular changes. The walls of the vessels are infiltrated with neutrophils and eosinophils (angiitis), the architecture of the pulmonary parenchyma is violated due to necrotic and granulomatous processes. The next important stage in the development of the theme of systemic vasculitis was introduced into the laboratory diagnostics of the determination of antine-hydrophilic cytoplasmic autoantibo (ANCA).

At the conference in Chapel Hill was allocated a group of primary systemic vasculites with a predominant defeat of respiratory organs. In this group included granulomatosis of venener, microscopic polyangiite and Chard Strauss syndrome. The granulomatous inflammatory process is characterized by the involvement in the pathological process of the vessels of small and medium sizes (capillaries, veins, arterioles, arteries), as well as detecting antibodies ANCA.

If in Russian-speaking medical literature, a vegetarian granulosis, microscopic polyangitis (E.L. Nasonov), then the Chard Strauss syndrome is mentioned as one of the forms of primary systemic vasculitis. This circumstance prompted the author when analyzing the forms of primary systemic vasculitis to stop mainly on Charge Strauss syndrome.

Charge Strauss Syndrome

Classification criteria for clinical manifestations charge Strauss Syndrome (SCH) Includes six main manifestations: asthma, eosinophilia\u003e 10%, mono- or polyneuropathy, volatile pulmonary infiltrates, sinusites, extravascular tissue eosinophilia (American College of Rheumatology, 1990). If the patient has four of these six signs, then the diagnostic sensitivity exceeds 85%, specificity is 99.7%. The central place is the bronchial asthma, which allows the doctor to navigate among other manifestations of systemic vasculites. Table 1 summarizes the diagnostic significance of certain manifestations of the SCS.

Morphology

Pathological changes in pulmonary fabric are not sufficiently studied. Cottin and Cordier lead a few pathological data in the pulmonary parenchyma. These changes are common and variable character; The most pronounced of them are necrotic changes and formation of a cavern. In many vessels, blood clots and sections of hemorrhages are detected, in later stages, the growth of scar connective tissue is detected. Histological changes at the SCC are characterized by a combination of necrotizing granuloma, vasculitis of small and medium vessels, as well as the development of eosinophilic pneumonia. In patients who were not treated with steroid preparations, extensive eosinophilic infiltrates are detected, mainly interstitial and perivascular.

Pathological changes in pulmonary fabric are not sufficiently studied. Cottin and Cordier lead a few pathological data in the pulmonary parenchyma. These changes are common and variable character; The most pronounced of them are necrotic changes and formation of a cavern. In many vessels, blood clots and sections of hemorrhages are detected, in later stages, the growth of scar connective tissue is detected. Histological changes at the SCC are characterized by a combination of necrotizing granuloma, vasculitis of small and medium vessels, as well as the development of eosinophilic pneumonia. In patients who were not treated with steroid preparations, extensive eosinophilic infiltrates are detected, mainly interstitial and perivascular.

The necrotizing inflammatory granuloma is located extravascular, in this pathological process of the vessels rarely are involved. Granuloma is characterized by the appearance of a necrotic zone, which is surrounded by epitheliodic histiocytes. For this type of granuloma, a typical significant content of eosinophils and shark-leiden crystals. In the motley morphological picture, sarcoid-like granulomas are also observed.

Another decisive sign of primary systemic vasculitis at the SCS is morphological changes in the walls of the vessels. Small arteries and veins are involved in the process, the walls of the vessels infiltrated by cells, the appearance of eosinophils and giant cells has a differential diagnostic value. The inflammatory response is at various stages of its development, therefore, in addition to acutely phase reactions, their outcomes are observed in the form of scarotic sclerotic changes in vessels and pulmonary fabric.

The morphological picture is complemented by changes from the bronchi and bronchiol, which are characteristic of bronchial asthma. The wall of the bronchi infiltrated by eosinophils, the mucous membrane, smooth muscles are in the state of hypertrophy, there is a metaplasia of glassworm cells, there is a significant thickening of the basal membrane, mucous tubes are formed in the lumen of the terminal respiratory tract. The interstitial tissue of the lungs, as well as the interaralwolar space, infiltrated with lymphocytes, plasma cells and histiocytes.

Transbronchial biopsy usually makes it possible to obtain sufficient material for a histological research, and only in rare cases is recommended for open biopsy of the lungs. Typical morphological features of vasculitis are pronounced infiltration by eosinophils wall of small vessels. An important sign of primary systemic vasculitis is the detection of necrotizing granuloma. These changes can be detected in the study of the skin and subcutaneous fiber.

Differential diagnostics of the SCS is carried out with vegetable granulomatosis, hyperoeosinophilic syndrome, nodule polyarteritis, microscopic polyangeitis; It does not represent difficulties, if we take clinical manifestations of primary systemic vasculitis as a basis. However, the morphological difference represents certain difficulties in the distinction of vasculitis close on its manifestations. The greatest diagnostic significance has necrotic vasculitis, eosinophilic pneumonia, extravascular granulomatosis, which are pathognomonic for the SCS. Thus, under the granulomatosis of venener, it does not occur intensive infiltration by eosinophils, while the formation of aseptic necrotic cavity is more characteristic of its early stages, and with the score, it is possible only at far-closed stages of the disease. Extravascular granuloma does not occur in the nodule polyarteritis, and the lungs damage is not a leading manifestation with vasculite. The differential diagnosis is more complex between chronic eosinophilic pneumonia and the core, since the infiltration of light eosinophils morphologically very close. The task is also complicated by the fact that in chronic eosinophilic pneumonia, the manifestations of moderately pronounced vasculitis can be detected. However, necrotizing granulomatosis occurs only with the score.

Clinical picture

Lanham et al. described three phases of clinical flow scho. Many factors can affect the natural course of illness, especially drug therapy. In typical cases, the disease begins with manifestations of allergic rhinitis, which is often complicated by polyposeous growths of the mucosa of the nose and the addition of sinusites and bronchial asthma. The first phase of the disease can continue for several years, and the main clinical syndrome is bronchial asthma. The second phase is characterized by a high content of eosinophils in peripheral blood and their migration expressed in tissue. At this stage, chronic eosinophilic infiltration of the lungs and the gastrointestinal tract is formed. The third phase of the disease is characterized by frequent and serious attacks of bronchial asthma and the appearance of signs of systemic vasculitis. The time interval between the emergence of symptoms of bronchial asthma and vasculitis is on average for three years (the case describes in the literature when it was 50 years old). It is believed that the shorter this interval, the unfavorant the forecast of the flow of the SCS. The disease can manifest itself at any age, but more often signs of systemic vasculitis fall on the fourth or fifth decade of life. Women are sick three times more often than men. According to epidemiological studies, in clinical practice, patients with granulomatosis of Vegenere are more common than patients with civic.

Bronchial asthma - one of the main syndromes of this primary systemic vasculitis; As a rule, its clinical manifestations fall on the older age group. The course of the disease immediately becomes difficult, which forces doctors in early dates to prescribe systemic corticosteroid drugs. The exacerbations of the disease are frequent, poorly controlled by the reception of moderate doses of steroids, doctors are forced to constantly increase them. Remissions are reduced, the intensity and severity of clinical manifestations of bronchial asthma increase. Similar forms of bronchial asthma are treated as heavy (malignant). With the advent of signs of systemic vasculitis, the severity of bronchial asthma may decrease; The generalization of the process is preceded by a period of long-term fever, pronounced intoxication with a decrease in body weight.

Another clinical feature of the flow of bronchial asthma - the appearance of pulmonary infiltrates. They are recorded in two thirds of the patients, which makes the diagnosis of Charge-Stross syndrome more likely. Infiltrates in the lungs can develop at different stages of the disease: during the appearance of the first attacks of choking or already during the expanded clinical picture of the systemic vasculitis. In diagnosis of infiltrates, x-ray methods of priming chest organs are crucial. Infiltrates are transitious, they can spread to the entire share of the lung, but more often localized in several segments. They are rapidly exposed to reverse development when prescribing glucocorticosteroid drugs, which can be used to form a diagnosis of the SCS. The shape and localization of infiltrates may be the most diverse; In cases where they are symmetrically arranged on the periphery, there is a need to differentiate them with chronic eosinophilic pneumonia. The nodes and bilaterally located infiltrates, in contrast to the vegetable granulomatosis, are rarely complicated by the formation of aseptic cavity. Infiltrates can be diffuse, spreading to the interstitial lung tissue; An increase in lymph nodes is rarely observed.

With the introduction of computed tomography into the clinical practice, the possibilities in the diagnosis of pulmonary vasculites have significantly expanded. It allowed visualizing parenchymal infiltrates, often similar to the "matte glass" phenomenon, located mainly along the periphery. With the help of computed tomography, changes are well detected from the bronchi, the walls of which are thickened; In some places, they dilated up to the formation of bronchiectasis. In some patients, nodal formations are revealed in the pulmonary fabric. ATTENTION Attracts changes from vessels that are better detected when conducting high-resolution computed tomography (they look extended, with pointed endings). These radiological finds correlate with eosinophilic infiltration of vessels walls and its propagation on the intermediate fabric.

Allergic rhinitis It is found more than 70% of patients with a sch. The clinical picture of the disease often begins with manifestations of rhinitis, which is complicated by the development of polyps in the nose, infiltrated by eosinophils and eosinophilic sinusites. However, in contrast to the granulomatosis of vegeter, when necrotic processes in the septal part of the nose lead to its perforation and development of the "saddle nose", with a similar kind of processes, rather, exceptions.

The clinical picture of systemic vasculitis is characterized by a large polymorphism of manifestations. SCHA has a special phase of the disease. with signs of systemic vasculitis. Usually, such general features such as fever, Malgia, Artralgia are joined to the manifestations of bronchial asthma and allergic rhinitis. In general, the clinical picture of the SCS is similar to the manifestations of the nodule polyarterita, but the signs of the kidney lesion is not observed. Lanham et al. The literary data was summarized in which the causes of death at the SCS were reported. At first, complications from the heart (increasing heart failure), hemorrhagic stroke and perforations in the gastrointestinal tract, were emerging, while the asthmatic state and other manifestations of respiratory failure were dominated in the clinical picture at the stage of deployed manifestations of systemic vasculitis. In that group of patients who had signs of renal failure, there was a need for differential diagnosis with a nodule polyarteritis.

If in the debut of the disease in the clinical picture, the SCS dominate the manifestations of allergic rhinitis and bronchial asthma, then with complicated forms of the disease, signs of stagnant heart failure or brain stroke are coming out. Eosinophilic granulomas can be localized in myocardium, which leads to a violation of the contractile function of myocardium. The damage to the coronary vessels, which occurs due to the inflammatory system process in the vessels, may be the cause of sudden death in this category of patients. On the miocardial defeat It was already indicated in a series of observations represented by Churg & Strauss. Cardiac activity can be improved during the period of successful carrying therapy with glucocorticosteroids and cyclophosphamide. The literature describes the patients who were successfully carried out by heart transplantation due to severe myocardial lesions at the SCS. It is recommended to carry out regular electrical and echocardiographic studies in patients with vasculitis. They often detect signs of mitral regurgitation, prognostic importance is identified by the diffuse fibrous process in myocardium. This diagnostic information is needed not only to state the fact that myocardium is involved in the inflammatory process, but it plays an important role in choosing adequate treatment methods and in the preparation of an individual disease flow forecast. Pericardius can be involved in the inflammatory process that with the defeat of the pleura and the accumulation in its cavity of the exudate creates a picture of the polyporosite. Endo Card is rarely involved in the inflammatory process, but clinical observations are described in the literature, which reported on endocardial fibrosis.

Defeat of the nervous system There is more than 60% of all patients with the SCC. Peripheral neuropathy comes to first place: mononeiropathy, distal polyneuropathy, is rarely observed asymmetric polyneuropathy. The basis of these manifestations is infiltration of epineural vessels lymphocytes, immunoglobulins, including IgE, as well as components of complement, immune complexes. Immunopathological processes in epineural vessels support the concept of systemic vasculitis. Less often meet radiculopathy, neuropathy of the optic nerve. Approximately every fourth patient appears signs of lesion of the central nervous system: from disorders in the emotional sphere to hemorrhagic stroke, brain infarction, epileptic phenomena. It is necessary to point out the possibility of developing adverse reactions from the central nervous system in response to corticosteroids or cytostatic therapy therapy, which sometimes it is quite difficult to distinguish from the symptoms of vasculitis.

Defeat kidneythe score is not frequent, and if such happened, they are usually not expressed. Thus, in the nodule, the polyarterite necrotic glomerulonephritis with segmental thrombosis is dominant, and the prognosis of patients depends on these manifestations. At the score, the prognostic value is the defeat of the heart and the vessels of the brain, but not the kidneys. However, with this form of vasculitis, proteinuria, hematuria, an increase in systemic blood pressure and initial signs of renal failure are observed. Especially this question was investigated by Guillevin et al., They produced a lifetime biopsy of the kidneys, and in a high percentage of cases the segmental glomerulonephritis was detected, which correlated with the detection of perinuclear antibodies (P-ANCA). With kidney damage, eosinophilic interstitial infiltrate, granuloma and vasculitis of renal vessels are rarely developed.

The lesion of the gastrointestinal tract is a relatively frequent clinical problem in patients with a sch. Vasculitis and eosinophilic infiltrate can lead to ischemia and subsequently - perforations of the wall of the stomach or intestines. It is necessary to again emphasize the possible negative effect of glucocorticosteroid therapy, the reception of which can cause the formation of acute ulcer of the stomach and subsequent bleeding. These complications may be the immediate cause of the death of patients with vasculitis.

Skin lesionsthe scores are quite frequent and can manifest themselves in the period of the debut of the disease. The most frequent skin manifestation with this form of vasculitis is the appearance of painful purple with predominant localization on the lower limbs. Subcutaneous nodules are preferably localized on the head and arms. However, it should be emphasized that this category of patients has no specific changes from the skin of the skin. The polymorphism of the skin symptoms can manifest the skin infarction, bullous, macular, papular or urticular rash. The diverse forms of skin lesions occur on the phase of the deployed clinical manifestations of the systemic vasculitis.

Poliarralgia and arthritis There are approximately each second patient with the score, especially during the system of system vasculitis. Poliarrults are often accompanied by Malgia. If Malgia is a relatively frequent manifestation of systemic vasculitis, then polyimiomyuses is practically not observed in sickness sick. In the diagnosis of the disease, the importance of muscle biopsy is given, as it can give enough objective information about the systemic vasculitis.

Ophthalmological complications With this form, vasculitis is rare. In the literature, separate observations of sick-sickers are given, which, due to ischemia, the optic nerve developed blindness.

Rare Localization Granuloma refers urogenital tract and prostate, which was the cause of the development of Anuria and obstructive uropathy. Separate patients described cases of autoimmune hemolytic anemia and cases of thrombosis, thromboembolism.

In pediatric practice, this form of systemic vasculitis is extremely rare. Described individual observations of the development of the SCS in women during pregnancy; The prescribed therapy with corticosteroid preparations provided persistent remission and successful delivery. However, observations described when they had to conduct artificial delivery due to the death of the fetus.

Laboratory diagnostics

Eosinophilia peripheral blood refers to the number of essential signs of the SCS. The number of eosinophils exceeds 1.5x109 / l (in relative quantities\u003e 10%), the boundaries of the percentage of eosinophils fluctuate from 11 to 77%. The high content of eosinophils and the clinical picture of bronchial asthma attacks make the diagnosis of the core more than likely. With the purpose of glucocorticosteroids, the content of eosinophils in peripheral blood is very quickly reduced to a normal level, and their increase can be considered as a sign of a starting exacerbation of systemic vasculitis. Eosinophilia is also detected in the study of bronchoalveolar lavage. In the process of therapy, glucocorticosteroids occurs, as mentioned above, a rapid decrease in the number of eosinophils in peripheral blood, as well as the regression of eosinophilic pneumonia, but this type of cells continues to be maintained in the alveolar portion of the boating liquid. High percentage content of eosinophils detect and in the study of pleural exudate.

Eosinophilia

Draws attention high content of general IGEHowever, the specificity of this indicator for the SCS is low.

Special attention in the laboratory diagnosis of vasculitis attached to detection anca antibodies. The increased antibody content is detected by more than 67% of patients. It is necessary to emphasize that antine-hydrophilic cytoplasmic autoantibodies (ANCA) are an antibody class of antibodies against antigen of cytoplasm of polymoretralical neutrophils, mainly proteinase-3 (PR3) and myeloperoxidases (MPO). When conducting an indirect immunofluorescence test, cytoplasmic (C-ANCA) and perinuclear antibodies (P-ANCA) are distinguished. The score is the most characteristic of the detection of perinuclear antibodies (P-ANCA) with anti-lifter oxidase activity, the cytoplasmic antibodies (C-ANCA) are less common. In patients with vegetable granulomatosis, elevated antibody titers with antiprotein specificity (PR3) are more often detected; With microscopic polyangeitis more often establish increased concentrations of perinuclear antibodies (P-ANCA); They are not detected in patients with a nodule polyarteritis. Serological diagnostics attaches great importance not only in the division of clinical forms of systemic vasculitis, but also in assessing the effectiveness of the therapy.

From other laboratory tests, the importance is attached to the study of the erythrocyte sedimentation reaction, which in this category of patients accelerates, in combination with hyperoeosinophylacy and an increased content of immunoglobulin class E has a diagnostic value. Anemia is rarely revealed, immune complexes and rheumatoid factor can be determined.

The fundamental importance in the laboratory diagnostics of the SCS is attached to the establishment of the fact of hypeozinophilia, an increase in the level of total IgE and perinuclear antibodies with anti-lifter oxidase activity (P-ANCA).

Diagnostics

Lanham et al. Developed SCS diagnostic criteriawhich includes bronchial asthma, hyperoeosinophilia\u003e 10% and systemic manifestations of vasculitis, when two or more organs are involved in the pathological process. These criteria in recent years have been complemented by positive tests on the content of ANCA antibodies. However, the diagnosis at the apparent clarity of the syndrome remains difficult. Churg & Strauss led observations of patients without glucocorticosteroid therapy, which allowed them to describe the natural course of the disease, when its clinical manifestations were not modified under the influence of therapy with hormonal drugs. In modern clinical practice, patients with bronchial asthma are already obtained in the early stages of the disease inhalation corticosteroids, and in cases of severe course, the reception of systemic hormonal drugs is added to this therapy. Such a tactic of patients has a significant impact on the manifestation of the SCS. In this situation, special attention should be paid to patients with a severe stream of bronchial asthma, with its frequent relapses and an unstable course of the disease. The abolition of glucocorticosteroids can provoke the transformation of the disease into the system of systemic manifestations of vasculitis and reducing the effectiveness of hormonal therapy, which has come due to resistance-developed resistance. In clinical practice, combined forms of vasculites are described, which also complicates the diagnostics of the SCS. Thus, the differential diagnosis is hampered in patients with the hyperoeosinophilia of other etiologies.

Causes of SCS factors

Naturally, the question arises about the causal factors leading to the development of the SCS. Much attention has always been paid to the connection of preceding infectious diseases and the development of primary systemic vasculitis. The authors of infectious hypothesis proceed from the fact that viruses and bacteria can contribute damage to endothelial cells, increased production of immune complexes, expression of cytokine genes responsible for the products of adhesive molecules. Bacterial antigens associate the amplification process of autoantigen such as proteinase-3 (PR3). Thus, the appearance of ANCA class antibodies is associated with an autoimmune process.

The viral theory of the occurrence of vasculitis has always remained in the spotlight. Vasculites are often associated with the persistence of hepatitis B and C viruses, as well as with the first-type immunodeficiency virus. Antibodies to the hepatitis B virus are often detected, but it is quite difficult to judge the causal relationship; more inclined to the fact that these are independent pathological processes.

The concept based on the fact of establishing increased production of Anca class antibodies was the greatest distribution. This group of autoantibodies is directed against various cytoplasmic antigens. In the cytoplasm of neutrophils found: myeloperoxidase, elastase, cathepsin G, lysosomes, lactoferrin, defense, azuroseidine and other connections. However, only antibodies to the cytoplasm of neutrophils (C-ANCA), perinuclear antibodies (P-ANCA) and antibodies with myeloperoxidase and proteinase-3 specificity and antibodies have diagnostic value. They associate the increase in the permeability of neutrophil membranes, and they are considered as biological markers of vasculitis. The mechanism of their formation remains little studied. There is a link between the formation of adhesive molecules, damage to endothelial cells, on the one hand, and the increased formation of antinerophilic antibodies (ANCA). An experimental model has been developed at which an increased synthesis of ANCA is reproduced. Silicone-containing compounds when they are introduced into the organism of animals stimulate the formation of antine-hydrofyl antibodies. It is assumed that this process is mediated through the inflammatory activity of neutrophils. A greatest role is played by genetic predisposition to the formation of inflammatory reactions of vessels flowing with the participation of antinerophilic antibodies. So, it was established that with a tripsin inhibitor deficiency, anca is an increased formation of ANCA CO specificity to Proteinase-3.

The tendency to allergic reactions in families, where there are patients with systemic vasculitis, also confirms the role of hereditary predisposition to such pathological conditions. The development of the core was observed after specific immunotherapy or vaccination (Guillevin et al.). It is assumed that the development of undesirable reactions occurred as a result of antigenic irritation by allergens or bacterial antigens of the immune system in patients with bronchial asthma.

Special attention is paid to the description of the SCS in patients with bronchial asthma, which were on the treatment of Zafirlukast. Inhibitors of leukotriene receptors (Zafirlukast) relatively recently began to be used in the treatment of bronchial asthma. A message about eight patients came to the American Pharmacope, which, after the reception of Zafirlukast, was developed (1999). However, the nature of vasculitis remained unclear, since patients who took this drug had a serious flow of bronchial asthma. Therefore, the question naturally emerged whether these patients were initially sick vasculitis, which manifested itself with a decrease in the maintenance dose of systemic glucocorticosteroids. Recently, single reports have emerged that after receiving another drug of this class (montelukast), symptoms of systemic vasculitis have also developed. Currently, doctors are not recommended to prescribe high doses of these drugs during the severe course of bronchial asthma, especially in those clinical cases when a suspicion of the SCS arises. When analyzing the histories of the diseases of patients with bronchial asthma, attention was drawn to the development of adverse reactions to the reception of Zafirlukast that most of them have identified signs of dilatation cardiomyopathy.

Treatment and schism forecast

The scholars forecast may be unfavorable if the patients do not receive adequate treatment. First of all, if therapy is not prescribed by systemic glucocorticosteroids, which help them quickly and efficiently. The initial dose is large enough and amounts to 1 mg / kg prednisolone per day, subsequently (a month from the beginning of therapy) it is quickly reduced. The course of therapy with glucocorticosteroids is designed for 9-12 months.

It is recommended to carry out careful control over the clinical condition of patients, based on the fact that the SCS is related to the number of systemic vasculites. In the focus of attention of the doctor must be all possible diseases: the central and peripheral nervous system, the upper and lower airway departments, the cardiovascular system, the gastrointestinal tract, the urogenital tract, vision, etc. Repeated studies of peripheral blood are carried out and the level of eosinophils is controlled, the rate of sedimentation of red blood cells. There are no clear recommendations for the dynamic observation of ANCA levels, which are attached to such great importance in the primary diagnosis of vasculitis. Persistent clinical remission and positive laboratory indicators allow you to go to an alternating method for receiving glucocorticosteroids. However, in clinical practice there are patients who develop resistance to corticosteroid therapy, which ultimately leads to exacerbation of the disease.

Anti-inflammatory therapy optimization can be achieved due to combined purpose of glucocorticosteroids and cyclophosphamide . The latter is prescribed at the rate of 2 mg per kg of body weight per day. Therapy is designed for a year; The dose of cyclophosphamide should be adjusted depending on the function of the kidneys and indicators of white blood.

With severe exacerbations, the core is shown plasmalresa ; With its use, the reduction of side effects is binding, which develop due to high doses of glucocorticosteroids and cyclophosphamide. With life-degrading exacerbations of the primary systemic vasculitis showed pulse therapy methylprednisolone (15 mg / kg intravenously introduced within one hour for 3-6 days). Some authors successfully applied the combination of methylprednisolone and cyclophosphamide in the form of pulse therapy (Cottin, Cordier).

The prognostic factor of the flow and outcome of the SCS is a polyorgan defeat; The forecast is particularly unfavorable when engaging in the process of systemic vasculitis of the heart and kidney. So, Guillevin et al. An unfavorable forecast includes patients whose daily proteinuria exceeds 1 g per day and serum creatin more than 140 μmol / l. The defeat of the central nervous system, and the gastrointestinal tract should be attributed to prognostically unfavorable factors. However, it should be emphasized that the forecast of the flow and outcome of the SCS significantly improved in the conduct of this category of patients on combined therapy with glucocorticosteroids and cyclophosphamide. The main position in the modern maintenance of primary systemic vasculites remains the principle of early diagnosis of the disease and the prevention of infectious and nuclear complications. The most dangerous complication is the development of pneumonia, the etiological factor of which most often acts Pneumocystis Carini.. Patients in combination therapy with glucocorticosteroids and cyclophosphamide, in order to prevent pneumonia, it is recommended to take trimethopris / sulfamethoxazole 960 mg per day three times during the week.

Other ANCA-Associate Vasculites

Therapeutic approaches to the treatment of sicc patients are not much different from those with vegetable granulomatosis and microscopic polyangeitis. However, the clinical picture of each of the specified forms of primary systemic vasculitis has a number of features.

So, with granulomatosis of Vegener One of the leading signs is the defeat of the ENT organs. The vasculitis is typical for this form is the development of a "saddot nose", which is due to the necrotic process with localization in the cartilage part of the nose. In lung fabric, more than 85% of patients are revealed granulomas. It should be emphasized that their localization may be the most diverse. However, in the granulomatosis of Vegener, even in those patients who have found signs of lung damage, bronchial asthma is not found, which can serve as an important differential-diagnostic sign that distinguishes the granulomatosis of veneran from the SCS. Serological diagnostics is of great importance in the diagnosis of vegetable granulomatosis. Positive tests for ANCA antibodies (especially C - ANCA / PR3 - ANCA or P - ANCA / MPO - ANCA) indicate a complicated course of the disease, when many organs are involved in the pathological process, many bodies are involved in the pathological process.

The third form of primary systemic vasculitis associated with ANCA antibodies is microscopic polyangiit. Its free

Etiology and CHARGE syndrome. CHARGE syndrome (MIM No. 214800) is an autosomal dominant disease with numerous congenital defects caused by most patients with mutations in the CHD7 gene. The estimated prevalence at birth is 1 to 3,000-12,000.

Nevertheless, the appearance genetic testing It can identify mutations of the CHD7 gene in atypical cases, which can determine higher occurrence.

Pathogenesis of Charge syndrome. CHD7 gene, sprinkled in 8Ql2, - a member of the DNA-bound chromium chromium helicase (CHD) genes. It is believed that the proteins of this family affect structural chromatin and the expression of genes during early embryonic development.

Gene CHD7 Expressed everywhere in a variety of fruit and adult fabrics, including eyes, snail ear, brain, CNS, stomach, intestines, heart, kidneys, lungs and liver. In patients with CHARGE syndrome, heterozygous nonsense and Missens-mutations were found in the CHD7 gene, as well as the deletion of the 8Ql2 section, the exciting CHD7 gene, proving that the disease causes happonated gene.

Nevertheless, some the patients With CHARGE syndrome, there are no detectable mutations in the CHD7 gene, so sometimes the disease can be mutations in other loci.

Phenotype and development of Charge syndrome

Acronym Charge. (C - Koloboma, H - Murned Defects, A - Atresia Hoan, R - Delay of Growth and Development, G - Anomalies Genitals, E - Ear Anomalies), covering the most frequent symptoms of syndrome, adopted by the dismortic fologists as the descriptive name of the Anomalia Association of Unknown Etiology and pathogenesis observed together more often than expected.

With the opening of mutations in the gene CHD7 In the CHARGE syndrome, the disease was attributed to disextempt syndromes, i.e. Characteristic sets of causally connected anomalies. Current basic diagnostic syndrome criteria - eye coloboma (exciting iris, retina, vascular shell or disc, with or without microftralma), atresia Hoan (one-sided or bilateral; stenosis or atresia), abnormal nerve (with one-sided or double-sided face paralysis, neurosensory deafness or swallowing problems) and characteristic hearing anomalies (the outdoor ear is deformed, a cup-shaped, in the middle ear of the videos of the development of auditory bones, mixed deafness and cochlear vices).

Less often find many other anomali, for example, cleft lips or nose, congenital heart defects, growth delay, trachecopic fistula or esophagus atresia. CHARGE syndrome is diagnosed with three-four specific criteria or two large and three small criteria.

Perinatal or early children mortality (up to 6 months of life), observed approximately half of the patients, correlates with the most severe congenital anomalies, including bilateral atresia Hoang and congenital heart defects. The significant cause of mortality and morbidity is a gastroesophageal reflux.

Often there are problems swallowing; Up to 50% of adolescents and adults need an installation of a gastrostomy tube. Most patients with Charge syndrome have behavioral anomalies (including hyperactivity, sleep disorders and obsessive behavior) and the delay in the occurrence of puberty. The delay in physical and mental development may vary from light to severe.

Insofar as study CHD7 mutation It reveals more and more individuals with Charge syndrome, its symptoms can become more studied, and the phenotypic spectrum will expand.

Features of the phenotypic manifestations of CHARGE syndrome:
Koloboma iris, retina, optical disk or optic nerve
Vices of the heart
Atresia Hoan.
Delay of growth and development
Innomalia sexual development
Ear Anomalies
Paralysis face
Cleft lips
Trachecopic fistula

Treatment of Charge syndrome

If it is suspected, a thorough examination is necessary to eliminate possible atresia or stenosis (unilateral) Hoang, congenital heart defects, centomials of the central nervous system, kidney, loss of hearing and hardening difficulties. Assistance includes surgical correction of malformations and careful care. An important component of observation is a dynamic status assessment. With the possibility of testing mutations in the CHD7 gene, at least 50% of patients can be mounted a molecular diagnosis.

CHARGE Syndrome Inheritance Risks

Almost all cases charge syndrome - a consequence of new dominant mutations with a low risk of repetition of parents. There is one known example of monosigital twins who had CHARGE syndrome, as well as one family with two sick sibsami (man and woman). The latter situation indicates that sexy mosaicism is possible. If a patient has a mutation in the CHD7n gene, both parents are negative for this mutation, the risk of repetition for future offspring is less than 5%. The patient has a 50% risk of repetition from offspring.

Example Charge syndrome. The girl was born on time at a 34-year-old primarmain mother with uncomplicated pregnancy. At childbirth, a cup-shaped shape of the ear shell on the right, with a turn of her for the stop. Because of the difficulty of feeding, the girl was transferred to the department of the pathology of newborns. An attempt to conduct a nasogastric probe to the right nostril was unsuccessful, which showed one-sided Atresia Hoan. Genetic suspected CHARGE syndrome.

Further survey Included with echocardiography, which has discovered a small defect of the interventricular partition, and an ophthalmological examination that has revealed the rifle of the retina in the left eye. The interventricular septum defect is corrected surgically without complications.

During newborn When screensing to reduce hearing, the test passed negatively, and the neurosensory deafness is subsequently diagnosed. Search for mutations in the CHARGE, CHD7 syndrome gene showed presence in exon 26 mutations 5418C\u003e G in a heterozygous state leading to the formation of premature stop codon (Tyr1806ter). The search for the mother's parents did not give, indicating that the mutation in the child occurred de Novo, so the family was informed about the low risk of repetition with future pregnancies. At the age of 1, the girl is moderately detained in the engine and speech development, its growth and body weight are in the 5th percentile, the head circumference - in the 10th percentile. Annual inspections are scheduled.