The histiocytosis is a generalizing name of a group of diseases for which the pathological overproduction and accumulation of cellular elements of the immune system (most often of the so-called Langerhans cells) located in various organs. In the future, infiltration (impregnation) of tissues of violated exchange products occurs, which leads to the development of pathological changes in organs and the violation of their functions.

Gisticiocytosis in children and adults

Pathology is considered a rare disease that is diagnosed in 1-5 patients from a million. Most often, it is already manifested in children's or adolescence. In adults, the disease is developing significantly less and occurs in chronic form. Among patients with various forms of histiocytosis, male patients prevail.

The mechanism of the occurrence of the disease is associated with a violation of the process of developing cells involved in an immune response. In the human body, they are represented by two cell lines, which are produced in the bone marrow:

1. True macrophages capable of capturing and eliminating antigens (viruses, bacteria, fungi, reborn own cells). There are macrophages circulating with blood flow - monocytes, and sedental cells in various tissues - histiocytes.
2. Dendritic cells (dendrocytes) capable of capturing and recognize the antigens penetrating into the body, as well as stimulate the response of the immune system. Dendrocytes pass several ripening stages, in the process of which they can circulate with a current of peripheral blood or on lymphatic vessels, and then settle in lymph nodes, tissues of the mucous or basal layer of the skin.

For the first time, dendritic cells were opened by Paul Langerhans, who mistakenly accepted them for nervous endings due to external similarity, and only after a century, Ralph Steinman defined their high ability to stimulate the protective mechanism of immunity. Over time, dendrocytes located in the skin epithelium, assigned the name of Langerhans cells.

Most often, the pathological growth is subject to Langerhans cells. Dendrocytes at the ripening stage are damaged and form accumulations, while continuing to generate an abnormal amount of proteins (cytokines, prostaglandins) capable of angry with the functions of surrounding cells from which the tissues of organs consist. Blood elements - eosinophils, neutrophils, phagocytes, rushed to the site of the growth of cells and form an infiltration that contributes to the border of tissues.

Symptoms of the disease depends on which the cells were subjected to proliferation (growth). With different forms of the disease, the changes affect not the entire body as a whole, but only individual organs. Most often, the pathological process occurs in the tissues of lungs, spleen, bones, lymph nodes, leather and liver. They meet both single cell growths that form localized tumors and do not affect the quality of life and massive tissue lesions leading to death.

Classification of histiocyte syndromes

Depending on the origin of pathological cells, three classes of histiocitary syndromes are distinguished:

1. I class - Pathology of dendritic cells:
   • histiocytosis X associated with the proliferation of Langerhans cells (Taratynov's disease, Abta-Letterier-Sweat Syndromes, Handa-Shuller-Chrischene);
   • juvenal Xantogranturn.
2. Class II - histiocyte syndromes caused by macrophage pathology:
   • hereditary or secondary hemophagocytic lymphogistocytosis;
   • virus-associated hemophagocytic syndrome;
   • tumor-associated histiocytosis;
   • sine histiocytosis with massive lymphadenopathy (Rosea-Dorfman's disease).
3. III class - malignant histiocytosis. The syndrome is characterized by the formation of tumors in the blood formation system. It can be caused by pathological growth:
   • monocytes (monocytic leukemia);
   • macrophages;
   • dendritic cells (malignant histiocytosis from Langerhans cells).

Depending on the scale of the propagation of the pathological process and damage to organs and systems, the following types of histiocytosis x are distinguished:

• monosystem - the disease affects only one body or system;
• polysystem - several organs and systems are affected immediately, the disease is characterized by rapid development and transition from one form to another;
• the same name - the accumulation of dendritic cells forms a benign single tumor, which can cause body dysfunction or to proceed asymptomatic;
• multicoping - multiple granules (nodules), affecting several organs at once.

Causes and factors of development

The reasons for the occurrence of the disease are specifically unknown, however, scientists identify several hypotheses of the origin of this disease:

• the pathology of immune regulation, in which the interaction of lymphocytes and macrophages is disturbed;
• hereditary nature of the disease - family cases are observed;
• autoimmune disorders in which cells intended to protect the organism on the invasion of alien genes attack their own tissues;
• the reactive response to an infection: for some forms of histiocytosis, the launchers are diseases caused by herpes viruses.

Since imported smokers or persons who were subjected to passive smoking, tobacco smoke among patients with light gistiocytosis are dominated by one of the factors of the development of the body's pathological immune response.

Features of histiocytosis from Langerhans cells - Video

Manifestations of various forms of the disease

Clinical manifestations in pathology are very diverse, which is due to the defeat of various organs and systems.

Taratynov disease (eosinophilic granule)

Taratynov's disease, or eosinophilic granule - the most frequent form of histiocytosis from Langerhans cells, it is diagnosed in 65% of cases. Single bone granule occurs in children's or youthful age. The disease is characterized by a slight, benign flow. The symptoms of the solitary (single) formation are the overtakers, swelling, fast fatigue. Often, the tumor is randomly detected during an x-ray examination. To suspect the presence of granules also allows blood test - for the disease, it is characterized by eosinophilia (an increase in the number of eosinophils is one of the leukocyte subspecies). The forecast in such cases is favorable.

In children under 5 years, Taratynov's disease is characterized by multiple lesion of flat bones (less than tubular) granules formed in their cavity containing the accumulation of eosinophilic leukocytes and foam cells. Most often, pathology develops in the bones of skull, femoral and pelvic bones, vertebrae. The granular-co-osteolatic process in the bones leads to an incorrect formation of a skeleton, frequent fractures, the formation of tumor-water nodes when localizing the focus on the bones of the skull. In small children, multiple eosinophilic granules may affect not only bone fabrics, but also mucous, skin and internal organs, which is accompanied by seborrheic dermatitis, increased liver and spleen.

Disease of Hend-Shuller-Chrischene (lymphogranulomatosis)

This form of the disease is diagnosed in children 2-5 years, less often in adults. The growth of Langerhans cells occurs in the skin, bones, lymph nodes and internal organs. The disease is characterized by the multiple formation of the granule in the bones of the skull (the area of \u200b\u200bthe eye, the base of the skull, frontal, temporal bone) and the damage of the hypothalamic-pituitary area are affected. Against the background of the deformation of the bones of the skull, chronic otites arise, leading to a decrease in hearing, protrusion or displacement of eyeballs (Exophthalm). Changes in the structure of the jaws lead to incorrect formation of bite and dental fraud. The hypothalamus and pituitary infiltration leads to a delay in the growth, mental development and puberty of the child.

In the occurrence of syndrome in adult symptoms appear in a decrease in libido, obesity in men in the female type, the development of mastopathy in both sexes. The characteristic signs of this form of the disease are non-soldering diabetes, unactering urination, bone xanthomatosis (lipid deposition), Pucheglasie. In the acute course of the disease, fabrics of lungs, liver, spleenki are affected. There are various skin rashes formed from dense papules, they are localized on the chest and in the axillary depressions. For the disease, changes in the blood pattern - eosinophilia, leukocytosis are also characteristic.

ABTA-Letterier-Sewe (malignant langergansocytosis)

One of the most dangerous varieties of malignant histoocytosis is diagnosed in infants and children under 3 years. The pathological growth of Langerhans cells occurs rapidly and affect lymph nodes, bone tissues, internal organs. The most expressed manifestations of skin infiltration - rash in the form of brown spots, eczema behind ear sinks, seborrhea scalp. Large papulas on the top of the body can be ulcerated. The lesion of the mucosa leads to the emergence of stomatitis, the density of the immature dentin desene, vulvovaginitis in girls.

Rosea-Dorfman's disease (N-helgerganasovy, or sine histiocytosis)

In sinus (NelHelgerase), histiocytosis develops inflammation and sealing of lymphoid tissue of cervical nodes and nasopharynx. There are characteristic changes in the structure of lymph nodes, of which the most significant feature is the expansion of sinuses. The disease has a protracted, recurrent character. Symptomatic manifestations are expressed in weakness, weight reduction, insomnia, high sweating and tendency to allergic reactions.

Virus-associated and hemophagocytaric syndromes

Hereditary hemophagocytic syndrome manifests itself in breast-age children. The cause of the disease is a mutation in the perforine gene, as a result of which the protein intended to protect the body from viruses is synthesized in insufficient quantity or there is no one at all. The disease has an unfavorable forecast.

The virus-associated hemophagocycration syndrome is considered a secondary disease provoked by viral infections in the main family of herpesviruses.

The clinical picture with these diseases is almost identical. The most frequent symptoms of the disease:

• liver dysfunction;
• an increase in spleen tissues;
• jaundice;
• skin rashes;
• soft fabrics;
• fever;
• pancitopenia (changes in blood composition);
• increased lymph nodes.

Violation of the functions of the dorsal and brain can manifest itself in neurological syndromes. The disease increases the risk of sepsis, which worsens treatment predictions.

Diagnosis of the disease

The diagnosis is made on the basis of the totality of symptoms, complaints of patient and external manifestations. To determine the form of the disease, laboratory tests and research are carried out:

1. Common blood test may show:
   • in Taratynov's disease - acceleration of ESP, leukocytosis and reduced hemoglobin levels;
   • under Latteter Sivey syndrome - an increase in ESP, neutrophilic leukocytosis;
   • with the disease, Handa-Shuller-chrischene - leukocytosis, hypergohilulinemia, acceleration of erythrocyte sedimentation, eosinophilia.
2. Macroscopic study of the affected tissue allows you to identify the accumulations of cell elements - eosinophils, plasma cells and macrophages.
3. Histological examination of tumors determines the presence of Langerhans cells.
4. Radiographic research reveals the presence of foci of degradation in the bones.
5. CT brain and lungs makes it possible to see damage in pituitary tissues and lungs.

The disease is differentiated with sarcoma, osteomyelitis, acute leukemia, congenital syphilis, mucopolysaccharideosis, tuberculosis.

Basic principles of treatment

The treatment regimen is appointed depending on the form of the disease, severity, as well as the volume and localization of damage to organs and tissues. With one-level eosinophilic granules of bones, spontaneous cure is possible.

Medical therapy

The main treatment of histiocytosis in the aggravation stage is the reception of the following drugs:

• corticosteroids - prednisone;
• cyticostatics - Hlorbutin, Azatioprin, Wincristine, Leikeran, Methotrexate.

The course of drug admission, as well as their dosage, prescribes a doctor, depending on the age and mass of the patient's body and the severity of the disease. Usually, drug treatment is carried out by cycles, where the course of the reception is replaced by an equal to the duration of the break. With positive dynamics, up to 10 cycles are prescribed.

At the same time, symptomatic treatment is carried out. The choice of drugs depends on the manifestations of the disease:

• with damage to the pituitary, Timalin, hypothiazide, decaris;
• during non-car diabetes, replacement therapy is recommended as desmopressin;
• with sine histiocytosis, interferon preparations are used;
• with broncho-referee - the broncho-tutor theophylline;
• vitamins are prescribed as a lining agent.

With damage to vital organs and systems, polyhemotherapy is prednisone, Vinblastin and Wepzid. In the diffuse damage of the skin or localized foci of granulomatosis, monochimotherapy is used, the selection is used by the drug.

Features diet and lifestyle

A specific diet does not exist, the principles of proper nutrition and a healthy lifestyle should be observed.

It is also recommended a refusal of bad habits. Especially harmful smoking, since smoke is annoying the mucous membrane of the respiratory tract, provoking the formation of cytokines and growth factors. The result of this process is the enhanced division of Langerhans cells.

Physiotherapeutic methods

In the event that bone damage in histiocytosis have multiple localization, use ionizing radiation therapy in the complex with glucocorticoids. With the risk of developing complications in the form of a spinal fracture, skeletal deformation, vision loss is prescribed megavolny radiation therapy.

Radiation therapy is contraindicated in eosinophilic lung granule, because it can provoke an aggravation of the disease.

Excimer laser apply to eliminate skin defects. In the process of exposure, the narrow-plated rays of the laser affect directly damaged skin cells. This technique allows you to slow down the pathological growth of histocytes, improve the condition of the skin.

Surgery

Operational intervention in histiocytosis from Langerhans cells are considered in the event of the low efficiency of radiation therapy. With the same foam monosystem damage, the bones use surgical intervention - Curetzhzh (scraping).

Folk remedies

Folk treatment methods are used for the disease to eliminate various manifestations:

1. Seborrheic dermatitis - the infusion of the Zverkoy. Dining-spoon of dry grass brew 0.5 liters boiling water and insist for half an hour. Revealing tincture in the same amount of boiled water and apply for wiping the amazed areas of the scalp.
2. Defeasure of adhesion with stomatitis - decoction of oak bark and sage. Crair Oak and Flowers Sage 5 g Pour water and boil for 10 minutes. Cool and strain, use twice a day to rinse the oral cavity.
3. Nonachar diabetes with diabetes - the infusion of plantain seeds. It is prepared as follows - 25 g of raw materials are poured 200 ml of boiling water and insist until a complete cooling under the lid. Then scramble and filter. Take 1 tbsp. l. 3 times a day before meals.
4. Pancitopenia (anemia) caused by chemotherapy - a decoction of rosehip and a vitamin mix of dried fruit with honey. Tea, cooked from the berries of red currant and rosehip fruits, improves blood composition and contributes to the elimination of anemia. Instead of currants, you can add rowan or strawberries. No less useful mixture of kuragi, figs, raisins, prunes and walnuts with honey and lemon. All products are taken in equal proportions, crushed through the meat grinder and stirred with honey. Tasty and useful dessert need to be used three times a day on a teaspoon.

Folk remedies for symptomatic treatment - photo gallery

Sage has healing, anti-inflammatory and bactericidal effect
Rubbernik's decoction is rich in vitamin C

3.1 conservative treatment.
Objectives of conservative treatment with GLC - the patient's cure, preventing reactivation (relapse) of the disease and preventing the formation of permanent complications. The therapy plan depends on the prevalence of defeat. With a monosystem unifocal lesion, local or topical therapy is carried out. With multifocal lesions and multisystems of GCL, it is necessary to conduct software chemotherapy. In reactivation of the disease, the therapy of the second line is carried out, the composition of which is determined by localization of the lesion and the involvement of "risk organs".
Patients with histiocytosis of Langerhans cells are recommended to conduct therapy for the first line according to the scheme:
Unifocal lesion of the skeleton.
Curetzh osteolatic focus.
Injections of corticosteroids in the lesion focus (dose 2 mg / kg body weight in prednisone).
Unifocal damage to the lymphatic node.
Excision biopsy affected lymphatic node.
Monosystem lesion of the skin.
Topic therapy with high efficiency corticosteroids.
Multisystem form or monosystem multifocal lesion of the skeleton The level of persuasive recommendations in (level of evidence level - 2).
The phase of initial therapy number 1 is recommended to be carried out according to the scheme:
Prednisone at a dose of 40 mg / m2 inward or intravenously in days 1-28, at a dose of 20 mg / m2 in days 28-35, at a dose of 10 mg / m2 in days 36-42. The level of persuasive recommendations in (level of reliability of evidence - 2).
The phase of initial therapy number 2 is recommended according to the scheme:
Vinblastine in a dose of 6 mg / m2 intravenously drip on days 1.8.15,22,29,36.
Prednisolone in a dose of 40 mg / m2 inside or intravenously on days 1-3, 8-10, 15-17, 22-24, 29-31, 36-38.

Comment.When the status of inactive disease (NED) is reached after the phase of initial therapy No. 1, supporting therapy should be started. When the response after the phase of initial therapy No. 1 of AZ-intermediate or AZ-improvement should be carried out by the phase of initial therapy No. 2. In the absence of an answer to the phase of initial therapy No. 1 (AZ-worsening), it is necessary to start performing the therapy of the second line.
Supporting therapy phase is recommended according to the scheme:

Supporting therapy cycles are carried out at intervals at 21 days for 40-46 weeks (total therapy duration of 52 weeks).
The level of persuasive recommendations in (level of reliability of evidence - 2).
The therapy of the second line in the reactivation of GLC without the involvement of "risk bodies" is recommended according to the scheme:
It is recommended to repeat the therapy of the first line.
The therapy of the second line in the involvement of "risk authorities" is recommended to be carried out according to the scheme:
Intensive phase (3 cycles).
2-chlordzeoxyenozin (2-CDA) at a dose of 9mg / m2 / day per days 1-5.
Cytosine Arabinoside (ARAC) at a dose of 500 mg / m2 / day in days 1-5.
Methylprednisolone 2 mg / kg / day per days 1-5.
Supporting therapy phase 1 (3 cycles).
2-CDA oxadenosine (2-CDA) at a dose of 5 mg / m2 / day per days 1-5.
Supporting phase therapy 2.
Vinblastine in a dose of 6 mg / m2 intravenously drip per day 1 cycle.
Prednisone at a dose of 40 mg / m2 inside or intravenously in days 1-5 cycles.
Vinblastine / prednisolone cycles are carried out at intervals of 21 days before the end of treatment (the total duration of therapy is 52 weeks).
The level of persuasive recommendations in (level of reliability of evidence - 2).
Comment.Combined highly visible chemotherapy 2-CDA and ARAC is associated with extended oral appliances and cell immunity deficiency. The program requires intensive accompanying therapy, which includes, but is not exhausted by the following components:
Patients with histiocytosis from Langerhans cells are recommended that transfusion of irradiated blood components.
Patients with histiocytosis of Langerhans cells recommended anti-hazy therapy, comprising drugs for intravenous and enteral administration, active with respect to mold fungi.
Patients with histiocytosis of Langerhans cells are recommended to provide access to the separation of resuscitation and intensive therapy, including technologies of renal substitution therapy. Conducting this therapy in the clinic that does not have access to the specified technologies is not recommended.
Recalculation of doses of chemotherapy products for patients with body weight less than 10 kg.
Vinblastine 6 mg / m2 \u003d 0.2 mg / kg.
Prednisolone 40 mg / m2 \u003d 1.3 mg / kg.
2-CDA 9 mg / m2 \u003d 0.3 mg / kg.
2-CDA 5 mg / m2 \u003d 0.15 mg / kg.
Therapy in special clinical situations.
Patients with histiocytosis of Langerhans cells with a neurodegenerative lesion of the CNS recommended the treatment of therapy according to the scheme:
Two options for therapy to choose from the attending physician.
Cytosine Arabinoside (ARAC) at a dose of 150 mg / m2 / day in days 1-5, 12 cycles with an interval of 28 days.
Immunoglobulin for intravenous administration at a dose of 0.5 mg / kg / exchange rate, 12 cycles with an interval of 28 days.
Patients with histiocytosis of Langerhans cells with tumor lesion CNS recommended the treatment of therapy according to the scheme:
2-CDA oxiaudenosine (2-CDA) at a dose of 5mg / m2 / day on days 1-5, 6 cycles with an interval of 28 days.
The level of persuasive recommendations in (level of reliability of evidence - 2).

3.2 surgical treatment.

The surgical allowance for HCL is performed at the diagnostic phase. The biopsy of the affected organ / tissue is performed in the amount necessary for the implementation of morphological, immunohistochemical and molecular biological research. In the unifocal monosystem damage, the skeleton is carried out by the curettage of education with the introduction of prednisolone in a dose of 2 mg / kg.

3.3 other treatment.

The accompanying antimicrobial and transfusion therapy is carried out in accordance with applicable clinical guidelines.

Tumor diseases, bone marrow pathology and blood cells, as well as idiopathic diseases (with unexplained etiology) in children have always been of interest to doctors and scientists, since they often have a complex treatment and / or unfavorable forecast. The histiocytosis of Langerhans in children is a disease that is characterized by the formation of a special type of granuloma in the tissues of various organs consisting of modified skin macrophages (cells first described by Paul Raggerhans at the end of the 19th century, performing an immune role).

Such pathology is considered a rather rare disease, since only 0.27 cases per 100,000 people are observed, And mainly in people from 20 to 40 years, and not in children. It occurs such histiocytosis according to various sources with the same frequency in both sexes. However, there is data of prospective observations, indicating the preferential detection of boys. The disease may affect flat bones, light, soft fabrics and skin, as well as pituitary gland. Of particular interest for medicine is the appearance of such granulomes in the pulmonary fabric of patients. This allows you to isolate the pathological process and to efficiently stop it.

Gistiocytosis of Langersance is a rare and quite dangerous disease for children of any age, so it is necessary to ensure its timely diagnosis, as well as take all measures to preserve the life of a small patient.

The main reasons for the occurrence of such a disease, as histiocytosis in children, until they are definitely installed. Despite the fact that histologically such a disease is quite easily diagnosed, as well as the doctors understand the main stones of the pathogenesis of the granuloma of this type in the tissues of the organs, there is a double approach to the definition of the main mechanism for the occurrence of the disease.

Currently, 2 theories of etiopathogenesis (causes and mechanisms of development) are dominated:

• immunological;
• tumor.

A number of researchers based on the fact that Langerhans cells are modified dendritic skin cells whose predecessors are the cells of the immune system, weigh an important role in the development of pathology precisely immunological theory. On the other hand, the very presence of atypical cells in the structure of the tissue, as well as specific granulomatous growth and low differentiation of cells gives a reason a number of scientists to put forward the tumor theory of the development of histiocytosis as the basis.

Doctors in clinical practice it is customary to associate the emergence and development of the disease with such factors:

1. Genetic and hereditary predisposition patient. There are a number of scientific papers indicating that the presence of certain options for genes in the child's DNA may lead to the development of such a rare disease.
2. Smoking. Despite the fact that 90% of adult patients are histiocytosis of Langerhans arose against the background of smoking, such a factor is difficult to discard in children. Tobacco smoke, falling into the lungs, due to its carcinogenic components and nicotine affects the activity of macrophages, which is possible and leads to provoking the granulomatosis of Langerhans. Knowing the peculiarities of the behavior of children of a particular adolescence when they try to smoke, this factor cannot be excluded as one of the causes of the disease.
3. Inhalation of aerosols of chemical toxins and dust. Considering the carcinogenic effect of some chemical compounds, as well as the mechanical impact of small dust fractions, such a reason can also be excluded as a factor provoking the development of this pathology.
4. Some viruses. Features of proliferative inflammation, as well as the active participation of the cells of the immune system in the formation of pathological foci in histoocytosis, are very similar to some well-studied infections (for example, tuberculosis, syphilis, etc.). However, in the study of the hectares of histoocytosis, bacterial pathogens were not detected. Viruses, in contrast to other microorganisms, due to replication inside the cells are very difficult diagnosed with common microbiological methods. Therefore, data on the fact that the role in the development of the disease takes such viruses as herpes, CMV, etc., not yet convincing, but also cannot be ignored.

Such a variety of predisposing factors and the lack of reliable data on the reasons does not allow at this stage to develop the effective measures for the prevention of histiocytosis.

Symptoms in children

The histiocytosis of Langerhans cells in children is characterized by the development of the following clinical picture, differing depending on the defeat of a particular organ:

• Skin lesion. Such a form of illness is more often found in very small children. It is manifested by rash and peeling of the skin according to the type of seborrheic dermatitis or eczema. Further, pathology can lead to the development of papules, white or brownish skin yasers, covered with crusts. The ineffectiveness of standard dermatological treatment and the rapidness of the development of the process allows the doctors to suspect a non-simple dermatological problem, but a general violation by the immune system.
• The lesion of the mucous membranes of the mouth and the gum by type of stomatitis.
• Light lesions - The occurrence of dry cough, shortness of breath, restrictive (associated with the impossibility of lungs to fully deal with breath) respiratory disorders, spontaneous pneumothorax.
• The occurrence of granuloma in flat bones, What is most commonly manifested by pain, unbound with injury, less often with pathological fractures of such bones.

A feature of the flow of this disease is non-specific symptoms and ease of flow at the initial stages. These symptoms, as well as rarely occurring such a disease, lead to the formulation of incorrect diagnosis at the beginning of treatment. The lack of the desired result from therapy, as well as the incessant increase in the severity of pathology, not only a doctor, but also parents. Rash on the skin is not similar to the frequent dermatological pathologies of children (allergic dermatitis, muscoses of the skin, scabies, etc.).

Despite the presence of such symptoms, cough and pain in the bones, there are no other signs of infectious pathology with histiocytosis. This is an important diagnostic sign.

Diagnosis of pathology

An examination of a child with histiocytosis begins with an inspection of the system of organs that is most worried about the child. Skin covers in the presence of rash are closely studied by a pediatrician and, if necessary, a dermatologist. The latter and appoints specialized "skin" surveys. Light children are listened to (auslined) pediatrician, respiratory infection and violations from the cardiovascular system are excluded. With pain in the bones additionally shows the consultation of the children's orthopedic traumatologist.

The standard survey group for a child who is suspected of the histiocytosis of Langerhans are:

1. Survey radiography of the chest organs. It allows you to differentiate the process from congenital abnormalities for the development of lungs and hearts, as well as inflammatory pathologies. Granulomas and cysts characteristic of such a disease are usually unable to be detected by this method.
2. CT (Computer Tomography Spiral Type) Chest More accurately gives the idea of \u200b\u200bthe morphology of the tissue of the lungs. Children characteristic of histiocytosis is the presence of multiple granuloma of incorrect shape, which can lead to the formation of small cysts in the pulmonary fabric.
3. Radiography of the area of \u200b\u200bthe bone where pathology is suspected. Allows you to assess the structure of tissues and identify a plot with a changed mineral density.
4. MRI head and spine. This study allows you to identify granulomas in the central nervous tissue department.
5. Skin biopsy, lung, bone or other organ with signs of pathology. The task of such a procedure is to take a sample of pathologically modified tissue for further histological analysis. It is a microscopic study that allows you to identify the cells of Langerhans, the granulomatous process and establish the child's accurate diagnosis.

Unfortunately, the diagnosis of such a disease is often delayed, and biopsy is carried out already at the stage of irreversible changes in organs and tissues, as well as the spread of the pathological process throughout the body. On the other hand, given the low probability of such a disease, as well as relative risks when conducting biopsy in children (especially internal organs), the priority in the diagnosis should be the exception of another, more common pathology. To do this, it is necessary to adhere to the tactics of a comprehensive examination and consulting related children's experts to conduct competent differential diagnosis.

Treatment and forecast

Therapy of histiocytosis of Langerhans includes the purpose of glucocorticosteroids and cytostatics, whose task to suppress the anomalous granulation growth of the tissue and abnormal immune responses. Treatment with these drugs requires special care from doctors in the selection of individual dosage, multiplicity of introduction and a common course of treatment.

Symptomatic therapy is also appointed to eliminate pain, general intoxication and respiratory symptoms. The reception of painkillers requires care for possible adverse reactions from the gastrointestinal tract, up to the development of ulcers and bleeding from it, which, against the background of taking strong cytostatics, can become fatal.

The forecast of the treatment of histiocytosis of Langergans is dubious and depends on the form of the disease. With localized pathology forms, it is quite common to achieve a resistant remission, which allows you to make a relatively favorable forecast for the patient's life. In generalized forms, more than 70% of patients, the forecast remains doubtful and unfavorable even with a comprehensive and intensive treatment.

Therefore, the earlier diagnosis and treatment of such a disease in children, regardless of age, is taken a special role.

Gisticiocytosis of Langerhans. In the risk group and children. Updated: March 5, 2017 by the author: admin.

Catad_Tema Oncology - Articles

Gisticiocytosis from Langerhans cells in children. Clinical recommendations.

GISTIOTIONS from Langerhans cells in children

МКБ 10: D76.0, D96.0.

Year of approval (revision frequency): 2016 (revision every year)

ID: Kr533.

Professional associations:

• National Society for Children's Hematology and Oncology

Approved

Agreed

Scientific Council of the Ministry of Health of the Russian Federation__ __________201_

osteolysis

Langherin

Immunohistochemistry

Chemotherapy

Vinblastine

Prednisolone

2-chldozeoxyadenozin

cytosine Arabinosid

permanent complications

List of abbreviations

GCL- GISTIOTIONS from Langerhans cells

PPC - Pathological cell of Langerhans

Alt- Alanin Aminotransferase

AST - Asparaginic Aminotransferase

GGTP - Gamma-GlutamylTranspendspendaz

LDH - lactate dehydrogenase

CT - Computer Tomography

MRI - magnetic resonance tomography

Ultrasound - Ultrasonic Study

HIV - human immunodeficiency virus

PCR - polymerase chain reaction

CMV - Cytomegalovirus

EBB - Epstein Barr virus

MSR + - Multi-system form of GCL with the involvement of "risk organs"

MSS- multi-system form of GLC without the involvement of "risk authorities"

Naz - inactive disease

Az - active disease

Terms and Definitions

Gisticiocytosis from Langerhans cells - a module of myeloid nature, the morphological substrate of which are pathological cells of Langerhans, phenotypically similar to Langerhans epidermal cells

Inactive disease (NED) - the status of a disease in which all reversible lesions have undergone reverse development

Active disease (AZ) - the status of a disease in which the initial or new lesion foci is preserved

Reactivation of the disease - the emergence of new lesions after the status of the name

Risk organs - organs (liver, spleen, bone marrow), whose involvement in the pathological process is associated with a poor prognosis of the disease

Permanent complications (software) are irreversible changes in the structure and / or function of organs in the outcome of the lesion during GKK.

Criteria for response to therapy

1. Brief information

1.1 Definition

Gisticiocytosis from Langerhans cells - a neoplasm of myeloid histogenesis with a variable clinical flow, which is based on the activation of the MEK-ERK signaling path in the precursor cells of dendritic cells. The localization of pathological foci is variable: the most common lesions of the skeleton, skin, the rear lobe of the pituitary gland, lymph nodes, liver, spleen, bone marrow, light and central nervous system.

1.2 etiology and pathogenesis

Gisticiocytosis from Langerhans cells develops as a result of the neoplastic transformation of dendritic cell precursors. The most detailed deciphered and common transforming molecular event is the somatic misstant mutation in the BRAF gene, leading to the replacement of the valine on glutamine in 600 position (denoted as BRAF V600E) and detected in 50-60% of patients. Alternative transforming mechanisms are also described, such as mutations in the MAP2K1 gene, ARAF gene, rare deletions / insertions in the gene show that all identified transforming events lead to the activation of the MEK-ERK signaling path. Is the activation of this signaling path to a sufficient mechanism for the formation of a clinical phenotype, or there are additional modifying genetic or epigenetic factors that determine the course of the disease remains the subject of study. The phenotype of the predecessors in which the transforming event or event occurs, also remains the subject of research. According to one of the theories, the transformation of resident tissue DCs forms the phenotype of localized GLC forms, while the transformation of bone marrow precursors DC leads to the development of disseminated forms of the disease. The GLK is characterized by infiltrating growth with the formation of the lesion of the characteristic cellular community in the foci, in addition to proper tumor cells, from a polymorphic leukocyte pool. The composition of the infiltration varies and may include eosinophils, t lymphocytes, giant multi-core cells and macrophages.

1.3 Epidemiology

Data on the incidence and prevalence of GLCs in Russia is limited, extrapolation of international data gives the incidence of 5-7 to 106 children's population per year. The ratio of floors is 2: 1 (M: D).

1.4 Coding on the ICD-10

D76.0 - histiocytosis from Langerhans cells, not classified in

C96.0 - Letterier-Zive

1.5 Classification

The histiocytosis from Langerhans cells is attributed to the group "L" in the modern classification of histiocytosis. Depending on the localization of the lesion, the monosystem form of the GLC is isolated, the multicipal form of HCL with the lesion of the "risk organs", the multi-mounted form of the GLC without damage to the "risk organs" and an isolated pulmonary gle. The risk authorities include liver, spleen and bone marrow. In the formulation of the diagnosis, in addition to the form of the disease, it is customary to indicate the anatomical localization of lesion foci.

2. Diagnostics

GLC diagnostics includes three stages: 1) establishing a clinical diagnosis and histological verification of GKC; 2) determination of prevalence / staging; 3) verification of the nature of the transforming event;

At the first stage, on the basis of the characteristic clinical manifestations (complaints, physical and primary laboratory and instrumental examination) establish a clinical diagnosis of GLC. Verification of the diagnosis is possible only on the basis of an immunohistochemical study of the biopsy material obtained from the lesion focus. The choice of biopsy zone is carried out on the basis of the principle of minimum invasion. Radical surgical interventions aimed at radical tumor removal are strictly contraindicated. The diagnosis is considered confirmed if, with a characteristic morphology of cell infiltration on pathological cell elements, the expression of CD1A or Langherin (CD207) is revealed. Based on systematic surveys, the prevalence of the disease is determined. Based on the molecular genetic study, there is a presence or absence of a BRAF V600E mutation. An example of a diagnosis formulation: histiocytosis from Langerhans cells, a multiciphered form with leather damage, skeleton and lungs, BRAF V600E-positive.

2.1 Complaints and history

The clinical presentation of GLC is diverse and reflects the prevalence of the process. Monosystem forms, especially the unifocal lesion of the skeleton of small-axis. Complaints and symptoms in multi-dimensional GLC form correspond to lesion loci.

• Main complaints
  • Fever
  • Eveny
  • Volume education
  • Polyuria
  • Polydipsy
  • Pain (back, limbs)
  • Increase the volume of belly
  • Separated from outdoor auditory passage
  • Diarrhea
  • Redued appetite
  • Delay of physical development
  • Psychomotor Development Delay
  • Loss of permanent teeth
  • Change behavior
    • Excitability
    • Anxiety
    • Drowsiness
• Anamnesis
  • Early child
  • Pregnancy and childbirth without pathology
  • Family history is not burdened
  • Smoking (with an isolated pulmonary GLC)

2.2 Physical examination

Physical examination, in addition to assessing the severity of state, physical and mental development, should be concentrated on identifying characteristic signs of defeat with GCC

• Rash (infiltrative spotful papular rash with a predominant location in natural folds, on the skin of the scalp)
• Exophthalm.
• Splenomegaly
• Hepatomegaly
• Lymphoenopathy
• Hemorrhagic rash
• Hemorrhage on mucous membranes
• Justice
• Volume formation associated with bone structures
• Status of the dental
• Signs of respiratory failure
• Delay in sexual development
• Focal neurological deficit
• Loss of indigenous teeth

2.3 Lab Diagnostics

• Automatic blood test with leukocyte formula
• Biochemical analysis of blood
  • bilirubin Common / Direct
  • Alt / Ast.
  • Albumen
  • Triglycerides (empty stomach)
  • Ferritin serum
  • Electrolytes
  • Creatinine
  • Urea
• Coagulogram
• Wizgly clinical analysis of urine
• Sampling Zimnitsky
• Morphological and immunohistochemical (CD1A and Langherin (CD207)) study of biopsy
• Mielograms
• Research of the concentration of serum immunoglobulins
• Detection of viral genomes by PCR in the blood (cytomegalovirus, Epstein-Barr virus, HIV, herpes Simplex 1 and 2 types, parvovirus B19)
• Molecular Genetic Research - Mutation Study BRAF. V600E by method with validated sensitivity of at least 5%.

2.4 Instrumental diagnostics

Patients with suspicion of histiocytosis from Langerhans cells are recommended:

• MRI brain T1, T2, Flair, with contrasts of gadolinium
• Abdominal ultrasound
• Radiography of the chest in a straight and lateral projection
• CT lungs

2.5 other diagnostics

Patients with suspicion of histiocytosis from Langerhans cells are recommended.

• Biopsy of volumetric / osteolatic formation with morphological and immunohistochemical studies
• Biopsy of the lymphatic assembly with morphological and immunohistochemical studies
• Skin biopsy with morphological and immunohistochemical research
• Liver biopsy with morphological and immunohistochemical research

3. Treatment

3.1 Conservative Treatment

Objectives of conservative treatment with GLC - the patient's cure, preventing reactivation (relapse) of the disease and preventing the formation of permanent complications. The therapy plan depends on the prevalence of defeat. With a monosystem unifocal lesion, local or topical therapy is carried out. With multifocal lesions and multisystems of GCL, it is necessary to conduct software chemotherapy. In reactivation of the disease, the therapy of the second line is carried out, the composition of which is determined by localization of the lesion and the involvement of "risk organs".

• Patients with histiocytosis of Langerhans cells are recommended to conduct therapy for the first line according to the scheme:

unifocal lesion of skeleton

• curetzh osteolatic focus

  injection of corticosteroids in the lesion center (dose 2 mg / kg body weight in prednisone)

unifocal lesion of the lymphatic node

• excision biopsy affected lymph node

monosystem leather damage

• topic therapy with high efficiency corticosteroids

multisystem shape or monosystem multifocal skeleton lesion

• prednisone at a dose of 40 mg / m2 inward or intravenously in days 1-28, at a dose of 20 mg / m2 in days 28-35, at a dose of 10 mg / m2 in days 36-42.

  Prevalence level of recommendations in (level of evidence of evidence - 2)

• vinblastine in a dose of 6 mg / m2 intravenously drip on days 1.8,15,22,29,36

  prednisolone in a dose of 40 mg / m2 inside or intravenously on days 1-3, 8-10, 15-17, 22-24, 29-31, 36-38.

Comment:when the status of inactive disease (NED) is reached after the phase of initial therapy No. 1, supporting therapy should be started. When the response after the phase of initial therapy No. 1 of AZ-intermediate or AZ-improvement should be carried out by the phase of initial therapy No. 2. In the absence of an answer to the phase of initial therapy No. 1 (AZ-worsening), it is necessary to start performing the therapy of the second line.

• supporting therapy cycles are carried out at interval at 21 days for 40-46 weeks (total therapy duration 52 weeks)

The therapy of the second line in the reactivation of GLC without the involvement of "risk bodies" is recommended according to the scheme:

The therapy of the second line in the involvement of "risk authorities" is recommended to be carried out according to the scheme:

• intensive phase (3 cycles)

  2-CHLORSODENOSEN (2-CDA) in a dose of 9mg / m2 / day in days 1-5

  cytosine Arabinoside (ARAC) at a dose of 500 mg / m2 / day in days 1-5

  methylprednisolone 2 mg / kg / day in days 1-5

  Supporting therapy Phase 1 (3 cycles)

  2-chlordzezedenozin (2-CDA) at a dose of 5 mg / m2 / day in days 1-5

  Supporting phase therapy 2

  vinblastine in a dose of 6 mg / m2 intravenously drip per day 1 cycle

  prednisone at a dose of 40 mg / m2 inside or intravenously in days 1-5 cycles

  winblastine / prednisone cycles are conducted at intervals of 21 days before the end of treatment (the total duration of therapy is 52 weeks)

Comment: combined highly visible chemotherapy 2-CDA and ARAC is associated with extended oral appliances and cell immunity deficiency. The program requires intensive accompanying therapy, which includes, but is not exhausted by the following components:

Patients with histiocytosis of Langerhans cells Recommended transfusion of irradiated blood components

Patients with histiocytosis of Langerhans cells Recommended antiharymalic therapy, including drugs for intravenous and enteral administration, active with respect to mold fungi

Patients with histiocytosis of Langerhans cells are recommended to provide access to the separation of resuscitation and intensive therapy, including technologies of renal substitution therapy. Conducting this therapy in the clinic that does not have access to the specified technologies is not recommended.

Recalculation of doses of chemotypes for patients with body weight less than 10 kg

vinblastine 6 mg / m2 \u003d 0.2 mg / kg

prednisolone 40 mg / m2 \u003d 1.3 mg / kg

2-CDA 9 mg / m2 \u003d 0.3 mg / kg

2-CDA 5 mg / m2 \u003d 0.15 mg / kg

Therapy in special clinical situations

Patients with histiocytosis of Langerhans cells with a neurodegenerative lesion of the CNS recommended the treatment of therapy according to the scheme:

Two options for therapy to choose from the attending physician

cytosine Arabinoside (ARAC) at a dose of 150 mg / m2 / day per days 1-5, 12 cycles with an interval of 28 days

Immunoglobulin for intravenous administration at a dose of 0.5 mg / kg / course, 12 cycles with an interval of 28 days

Patients with histiocytosis of Langerhans cells with tumor lesion CNS recommended the treatment of therapy according to the scheme:

• 2-CDA oxadenosine (2-CDA) at a dose of 5mg / m2 / day in days 1-5, 6 cycles with an interval of 28 days

3.2 Surgical treatment

The surgical allowance for HCL is performed at the diagnostic phase. The biopsy of the affected organ / tissue is performed in the amount necessary for the implementation of morphological, immunohistochemical and molecular biological research. In the unifocal monosystem damage, the skeleton is carried out by the curettage of education with the introduction of prednisolone in a dose of 2 mg / kg.

3.3 Other treatment

Accompanying antimicrobial and transfusion therapy are carried out in accordance with current clinical guidelines

4. Rehabilitation

Approach to rehabilitation and dispensary observation of patients with GLK. The dispensary observation includes systematic inspections and a targeted laboratory and instrumental examination, aimed at assessing the status of the initial lesions of the lesion and identifying new areas of the defeat. Examination and recommended intervals are shown below.

Clinical inspection 1 time in three months

Anthropometry 1 time in three months

Policy assessment 1 time per year

Clinical blood test 1 time in three months

Biochemical blood test 1 time in three months

Radiography of the affected areas of the skeleton according to the testimony

CT lungs (with initial involvement) 1 time per year

Ultrasound liver with elastography 1 time per year

(when initial involvement)

MRI brain 1 time per year

(Patients with initial damage to the central nervous system, unacceptable diabetes)

Consultation of the neurologist 1 time in six months

Consultation of endocrinologist 1 time per year

5. Prevention and dispensary observation

Primary prevention of GLC is impossible due to low base morbidity and unidentified causes of the disease.

Prevention of the reactivation of the disease and development of permanent complications is based on the full implementation of the protocol of therapy of the first line

The secondary prevention of the progression of permanent consequences includes exclusion of exposure to additional damaging factors, such as smoking in fibrosis of the lungs and infection with hepatitis viruses (A, B, C) when liver fibrosis.

Criteria for assessing the quality of medical care

Bibliography

1. Rollins BJ. Genomic aliates in Langerhans Cell Histioocytosis. Hematol Oncol Clin North Am. 2015; 29 (5): 839-51.
2. Collin M, Bigley V, McClain KL, Allen CE. Cell (S) of Origin of Langerhans Cell HistioCytosis. Hematol Oncol Clin North Am. 2015; 29 (5): 825-38.
3. Emile JF, ABLA O, Fraitag S, Horne A, Haroche J, Donadieu J, et al. Revised Classification of HistioCytoses and Neoplasms of the Macrophage Dendritic Cell Lineages. Blood. 2016; 127 (22): 2672-81.
4. Arico M, Egeler RM. Clinical Aspecs of Langerhans Cell Histioocytosis. Hematol Oncol Clin North Am. 1998; 12 (2): 247-58.
5. MONSEREENUSORN C, RODRIGUEZ-GALINDO C. Clinical Characteristics and Treatment of Langerhans Cell Histioocytosis. Hematol Oncol Clin North Am. 2015; 29 (5): 853-73.
6. Picarsic J, Jaffe R. Nosology and Pathology of Langerhans Cell Histioocytosis. Hematol Oncol Clin North Am. 2015; 29 (5): 799-823.
7. Schmitz L, Favara BE. Nosology and Pathology of Langerhans Cell HistioCytosis. Hematol Oncol Clin North Am. 1998; 12 (2): 221-46.
8. Meyer JS, De Camargo B. The Role of Radiology In The Diagnosis and Follow-Up of Langerhans Cell Histioocytosis. Hematol Oncol Clin North Am. 1998; 12 (2): 307-26.
9. Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, et al. A RANDOMIZED TRIAL OF TREATMENT FOR MULTISYSTEM LANGERHANS "CELL HISTICYTISIS. J PediaTr. 2001; 138 (5): 728-34.
10. Gadner H, Grois N, Potschger U, Minkov M, Arico M, Braier J, et al. Improved Outcome In Multisystem Langerhans Cell HistioCytosis Is Associated with therapy Intensification. Blood. 2008; 111 (5): 2556-62.
11. Gadner H, Minkov M, Grois N, Potschger U, Thiem E, Arico M, et al. Therapy Prolongation Improves Outcome In Multisystem Langerhans Cell Histioocytosis. Blood. 2013; 121 (25): 5006-14.
12. DONADIEU J, BERNARD F, VAN NOESEL M, BARKAOUI M, BARDET O, MURA R, ET AL. CLADRIBINE AND CYTARABINE IN REFRACTORY MULTISYSTEM LANGERHANS CELL HISTICYTISIS: Results of An International Phase 2 Study. Blood. 2015; 126 (12): 1415-23.
13. Imashuku s, Arceci RJ. Strategies for the prevention of Central Nervous System Complications in Patients with Langerhans Cell HistioCytosis: The Problem of Neurodegenerative Syndrome. Hematol Oncol Clin North Am. 2015; 29 (5): 875-93.

Appendix A1. Composition of the Working Group

Maschan G.A. - D.N., Deputy. Director General of the FGBU FNCC DGOI. Dmitry Rogachev, Professor of the Department of Hematology, Oncology and Radiation Therapy, Professor of the Department of Hematology, Oncology and Radiation Therapy Rnim. N.I.Pirogova Rnim him. N.I.Pirogov

Novichkova G.A. - D.N., Deputy. Director General of the FGBU FNCC DGOI. Dmitry Rogachev, Professor of the Department of Hematology, Oncology and Radiation Therapy, Professor of the Department of Hematology, Oncology and Radiation Therapy Rnim. N.I.Pirogova Rnim him. N.I.Pirogov

Maschan A.A. - D.N., Deputy. Director General of the FGBU FNCC DGOI. Dmitry Rogachev, Professor of the Department of Hematology, Oncology and radiation therapy of the Pediatric Faculty Rnim. N.I.Pirogov

Rumyantsev AG, D.M., Academician of the Russian Academy of Sciences, General Director of FGBC FNKTS DGOI. Dmitry Rogachev, Professor of the Department of Hematology, Oncology and radiation therapy of the Pediatric Faculty Rnim. N.I.Pirogov

There is no conflict of interest

Pediatrics31.08.19

1. Hematology31.08.29
2. Children's oncology31.08.14
3. Allergology and immunology31.08.26

Table P1 - levels of reliability of evidence

Level of confidence	Source evidence
	Prospective randomized controlled studies A sufficient number of studies with sufficient capacity, with the participation of a large number of patients and obtaining a large amount of data Large meta-analyzes At least one well-organized randomized controlled study Representative sample of patients
	Prospective with randomization or without a study with a limited amount of data Several studies with a small number of patients Well-organized prospective research cohort Meta-analyzes are limited, but carried out at a good level. Results are not presented with respect to the target population Well organized studies "case-control"
	Nerangerized controlled studies Studies with insufficient control Randomized clinical studies with at least 1 significant or at least 3 minor methodological errors Retrospective or observational research A series of clinical observations Conflicting data not allowing to form a final recommendation
	Expert's opinion / Data from the report of the Expert Commission, experimentally confirmed and theoretically substantiated

Table p2. - Levels of persuasive recommendations

Level of persuasive	Description	Decoding
		Method / first line therapy; either in combination with standard methods / therapy
		Method / therapy of the second line; Either when refusing, contraindicated, or the inefficiency of the standard technique / therapy. Recommended monitoring side effects
	there is no convincing data on the benefits or risk)	There are no objections against this method / therapy or there are no objections to the continuation of this method / therapy.
	The lack of convincing publications I, II or III level of evidence showing a significant superiority of benefits over risk or convincing publications I, II or III of the level of evidence showing a significant superiority of risk over benefits

Appendix B. Patient Leading Algorithms

Algorithm for selecting therapy in the multi-system form of histiocytosis from Langerhans cells with the involvement of "risk authorities"

Appendix B. Information for patients

Gisticiocytosis from Langerhans cells is a rare disease caused by a mutation in one of the types of leukocytes - dendritic cells. This mutation is not hereditary, occurs in the process of developing bone marrow cells in the patient's body and leads to the appearance of a mutant cell and its descendants of new properties: "wrong" dendritic cells can migrate to various organs and cause them damage. The main types of damage are shown below.

The defeat of the skeleton: the bones are formed foci of destruction, from the only thing to multiple. Sometimes a fracture may happen at the destroyer.

Skin lesions: Western brown rash with scales, often located in the folds of the skin and on the hair of the head of the head

Light damage: small areas of inflammation are formed in the lungs, which turn into emptiness similar to bubbles.

Bone marrow: As a result of the damage, the bone marrow produces blood cells poorly, as a result, hemoglobin, leukocytes and platelets are reduced in blood test.

Liver: As a result of the liver damage, its function is disturbed, changes in the biochemical analysis of blood, jaundice due to the increase in the content of bilirubin and swelling due to decrease in albumin production.

The rear share of the pituitary gland: the production of antidiuretic hormone is disturbed - the fluid balance controller in the body, as a result, a sharply enhanced selection of urine (diabetes) and thirst appears. Such a defeat is called "Nonachar Diabetes".

Head Brain: When the brain is damaged, the gait, memory, other nervous processes may be disturbed, depending on the brain section in which the defeat occurred

The disease can easily proceed, with localized lesion, spontaneous recovery is possible. With a common damage to the violation of the function of organs create a threat to the patient's life. The forms of the disease are particularly difficult, in which the so-called "risk bodies" is amazed - liver, spleen and bone marrow. For any forms of illness, a constant violation of its function can sometimes be formed as a result of the body of the body, which cannot be corrected. These defeats include fibrosis of lungs and liver, as well as non-sold diabetes.

To establish a diagnosis, it is necessary to perform a large number of blood studies, bone marrow puncture, X-ray and tomographic studies. It is necessary to fulfill the biopsy of the affected organ. Most often make biopsy skin, bone or lymphatic node. Without the results of the biopsy, the diagnosis of histiocytosis from Langerhans cells cannot be confirmed and therapy cannot be appointed.

The treatment of histiocytosis from Langerhans cells consists of two stages: the intensive phase of therapy and supporting therapy. During the intense phase, chemotherapy is carried out at small intervals, the patient in the hospital is often necessary. During maintenance therapy, the introduction of drugs and blood tests is required less often, the treatment is carried out outpatient. Chemotherapy of the first line consists of two main drugs: Vinblastine and prednisone. For patients with damage to risk organs, it is often necessary to conduct therapy of the second line - highly visible chemotherapy by other drugs.

The goal of therapy is the cure of the disease, preventing recurrences and late complications. The total duration of therapy is 1 year. Reducing therapy duration can lead to an increase in the risk of recurrence of the disease. For therapy in accordance with modern treatment programs, the probability of recovery is about 90%, but 25-40% of patients after recovery are complications, most frequent - non-soldering diabetes.

The choice of therapy is determined primarily by the prevalence of the process. In modern therapeutic programs, the use of systemic chemotherapy in all cases of polyorgan lesion is recommended. With regard to localized forms, there is a significant variety of approaches - from expectant tactics before conducting systemic chemotherapy.

Treatment with monosystem form of histiocytosis from Langerhans cells (GKK)

Despite the large differences in the staging of the disease, various approaches to the treatment and evaluation of its effectiveness, all clinical studies relating to histiocytosis from Langerhans cells (GLC) (even the earliest) uniquely indicate an exceptionally favorable forecast with an isolated bone defeat. In this regard, the testimony for the treatment of this form of histiocytosis from the cells of Langerhans (GLC) was significantly narrowed.

Currently prescribed treatment only in the presence of painful syndromeViolating motor functions, increased risk of disability. The type of therapeutic effect depends on the localization of the defect and the age of the patient. The scraping is a method of choice with small foci of destruction in bones that do not carry heavy loads, and is usually combined with biopsy at the diagnostic stage. With more extensive foci, as well as in places where scraping can lead to an unacceptable weakening of the bone, a tre-panobiopsy is recommended with the introduction of a depot-methylprednisolone in a dose of 100-150 mg.

For ineffectiveness of the first two ways Or in cases of lesions with hard-to-reach for surgery, localization is recommended U-irradiation, with the exception of young children. The total focal dose of irradiation should not exceed 5-8 grams due to the high sensitivity of the detection areas for radiation. In multifocal bone system damage, a monotherapy of corticosteroids is recommended, for example, prednisone at a dose of 1 mg / kg per day for 14 days, or preparations from a group of vegetable alkaloids (vincristine, vinblastine). Further therapy depends on the result obtained.

There are reports by successful use of IFN-A In adults, but in pediatric practice there is no sufficiently convincing data on its effectiveness.

For isolated lesion of skin in newborns With Hashimoto-Pritzker syndrome (congenital self-hearing histiocytosis) therapy is not required.

Dal-HX 83/90 protocol, intense phase.

A - all patients with multiciphered GLK: I - WEPENSID 150 mg / m2 per day, days of administration: 18, 25, 32 and 39th; II - WEPENSID of 60 mg / m2 per day, days of administration: from the 1st to the 5th; III - Vinblastine at 6 mg / m2 per day, the days of administration: from the 1st to the 28th; IV - prednisone at 40 mg / m2 per day, days of administration: from the 1st to the 28th.

B - group B - patients with multiciphered GLCs without organ dysfunction: I - WEPENSID 150 mg / m2 per day, days of administration: 15, 22, 29, 36th; II - WEPENSID of 60 mg / m2 per day, days of administration: from the 1st to the 5th; III - Vinblastine 6 mg / m2 per day, administration days: 15, 22, 29, 36th; IV - prednisone at 40 mg / m2 per day, days of administration: from the 1st to the 28th.

B - group C - patients with multiciphered GLCs with organ dysfunction: I - WEPENSID 150 mg / m2 per day, days of administration: 1, 8, 15, 22, 29, 36th; III - Vinblastine 6 mg / m2 per day, administration days: 1, 8, 15, 22, 29, 36th; IV - prednisone at 40 mg / m2 per day, days of administration: from the 1st to the 28th.

Treatment with polysystem form of histiocytosis from Langerhans cells (GKK)

Polysystem form of histiocytosis from Langerhans cells It is about 25% of all cases of the disease. A significant improvement in the results of treatment with this form of histiocytosis was noted with the beginning of the use of polychimotherapy.

At one time step Forward, treatment was treated according to COP / COPP schemes, however, the level of total survival was about 60%, and the non-dedicious - 40%, which was dictated by the need for further intensification of therapy.

First 80s xx century The German protocol DAL-HX-83 began to apply. The main concept of the protocol was the conduct of intensive induction therapy with corticosteroids and chemotherapy, most active in respect of the histiocytic range cells (Vinblastin, etoposide). The protocol did not assume the division of patients into risk groups. In the modification of the DAL-HX-90 protocol, all patients received intense induction therapy, the supporting therapy was carried out according to the risk separation. The total and unrecognizable survival rate of patients according to DAL-HX-83 and DAL-HX-90 protocols was 80 and 60%, respectively. These results were significantly better than those observed after the previously used therapy schemes.

FROM 1991 An international multicenter clinical study of the LCH-I protocol has begun. In this protocol, the allocation of risk groups was based on standard principles. Corticosteroids remained basic drugs, as well as vinblastine and etoposide, the comparative effectiveness of which was investigated in randomized groups. All patients received a short rate of corticosteroid therapy, the purpose of which was to relieve the systemic inflammatory reaction, then the patients were obtained by monotherapy with etopo-zide or vinblastine according to randomization.

Equal effectiveness of both drugs, However, the overall results of the protocol, especially in patients with a multi-system form, significantly inferior to the results of the DAL protocol: so, the non-dedicated survival rate was only 43%. Since 1994, another version of the LCH-II protocol has been proposed, in which high-risk patients receive intensive induction chemotherapy using a combination of etoposide and vinblastine with corticosteroids. The results of this protocol have not yet been published. The LCH-II protocol design is presented in Fig. 45.7.

It should be noted that one of of the most important prognostic factorsdetermining the outcome of the histiocytosis from Langerhans (GCC) cells, regardless of the protocol used, is the answer to induction therapy. It is shown that patient mortality that do not have any response after 6 weeks is from 66 to 100% according to different authors.

The answer to the initial therapy is independent prognostic factor With high significance and can be used to correct the tactics of treatment at an early stage of therapy and for the timely transfer of patients with a bad outlook on alternative therapy.

Thus, the main factors of an unfavorable forecast for polysystem gisticiocytosis from Langerhans cells (GLC) are: a multisystem version of the disease, the presence of dysfunction of the liver and hematopois, no response to the initial therapy.

LCH-II protocol (risk stratification).
A: I - prednisone 40 mg / m2 per day inside, the days of administration: from the 1st to the 28th, followed by a weekly reduction in the dose; II - WEPENSID 150 mg / m2 per day intravenously drip, administration days: 1, 8, 15, 22, 29, 36th; III - Vinblastine 6 mg / m2 per day Intravenously stinno, days of administration: 1.8, 15, 22, 29, 36th.
B: I - prednisone at 40 mg / m2 per day inside from 1st to 5th day weeks: 9, 12, 15, 18, 21, 24th;
II - WEPENSID 150 mg / m2 per day intravenously drip in the 1st day weeks: 9, 12, 15, 18, 21, 24th;
III - Vinblatin at 6 mg / m2 intravenously in the 1st day of weeks: 9, 12, 15, 18, 21, 24th; IV - 6-mercaptopurine at 50 mg / m2 per day inside from the 6th to the 24th week.

As therapy of the second line in patients who did not respond to standard therapeutic schemes, a combined immunosuppressive therapy was used at different times, alternative chemotherapeutic programs and a bone marrow transplant. The effectiveness of combined immunosuppressive therapy with antithimocyte globulin and cyclosporine A in patients (LCH-S protocol), refractory to therapy under the LCH-II protocol, was extremely low. Of the 13 patients incorporated into the LCH-S study, only one has a complete remission of the disease. The most promising in the treatment of refractory forms of histiocytosis from Langerhans (GLC) cells are nucleoside analogues of a new generation.

In particular, in recent years, several reports on the successful use of 2-chloride oxyadenosine appeared ( cladribibin). The first report on the effectiveness of Claporbina in two adult patients with common skin histiocytosis appeared in 1994. Subsequently, it was shown that cladribbin is effective in both adults and children, with the most severe, refractory to standard therapy with histoocytees.

2-CDA is purin analogue which is subjected to metabolic activation in cells under the action of the enzyme deoxycytidin-kinase. Active metabolites 2-CDA violate the processes of replication and DNA repair and, unlike classical antimetabolites, have a toxic effect on both divided and mature cells. In our experience, out of 5 children with multi-system histiocytosis from Langerhans (GLC) cells, refractory for therapy under the LCH-II protocol, three received a complete remission of the disease, one has been achieved by clinical improvement and one patient died from the progression of histoocytosis and developed on his background fungal sepsis.

Bone marrow transplantation in histiocytees from Langerhans cells (GLC) remains an experimental method of therapy, its effectiveness has not been proven.