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INVENTION
Patent of the Russian Federation RU2268737

METHOD FOR TREATMENT OF ATOPIC DERMATITIS

The name of the inventor: Malysheva Olga Alexandrovna (RU); Nepomnyashchikh Vera Makarovna (RU); Leonova Marina Ivanovna (RU); Shirinsky Valery Stepanovich (RU); Kozlov Vladimir Alexandrovich
Name of patent holder: State institution Institute of Clinical Immunology SB RAMS
Address for correspondence: 630099, Novosibirsk, ul. Yadrintsevskaya, 14, State Institution Research Institute of Clinical Immunology, Siberian Branch of the Russian Academy of Medical Sciences
Date of commencement of the patent: 2004.02.16

The invention relates to medicine, viz., Dermatology, and relates to the treatment of atopic dermatitis. For what purpose are prescribed antihistamines, detoxification therapy, local glucocorticoid-containing ointments and immunomodulating drug hormone epiphysis melatonin at a dose of 3 mg at 21.00 hour rate of 21 days. This method ensures the effectiveness of treatment by reducing the level of IgE.

DESCRIPTION OF THE INVENTION

The present invention relates to medicine, and more particularly relates to a method of treating atopic dermatitis.

The present invention can be used in various fields of medicine, for example, in allergology and immunology, dermatology, neuroimmunology.

Treatment of patients with atopic dermatitis is an important problem of allergology, immunology and dermatology, since effective methods of controlling the disease and treating its relapses have not been developed [1]. The standard treatment methods used for treatment, including the use of local and systemic drugs, do not allow full control of the disease [2]. Therefore, the development of new protocols for the treatment of patients with atopic dermatitis, which have greater therapeutic efficacy [13]. Prospects for the treatment of atopic dermatitis are associated with the use of various immunomodulators, since atopic dermatitis is a disease of an immunological nature and is often complicated by signs of secondary immune deficiency in the form of pyoderma and a decrease in a number of immune system indicators [8]. Atopic dermatitis is based on complex disorders of the immune system, including the development of allergic reactions to various allergens, the pathological process being localized mainly in the skin, and the formation of immune deficiency in the cellular and macrophage links of the immune system, the development of which is associated with the attachment of a secondary bacterial infection of the skin , Worsening of the course of the disease [9, 10].

A method of treating patients with atopic dermatitis is known when an immunomodulator is added to the standard therapy of atopic dermatitis in order to correct immune deficiency and reduce the clinical manifestations of the disease. (Biology, Section 04K1 Immunology Allergology, No. 10, 2000, p.48, abstract 00.10-04K1. 420, Syndrome of secondary immune insufficiency in patients with allergic diseases and methods of its correction / Luss LV, Mikheeva GN, Tuzlukova EB, Tsarev SV // g. Physician 2000. - №4. - С.24-27), which consists in the use of the immunomodulating drug in patients with atopic dermatitis - polyoxidonium (polyoxidonium - a water-soluble derivative of heteroceptive polyamines, a high-molecular analogue of many physiologically active compounds widely available in nature, has a pronounced immunotropic activity [6]), Characterized by the fact that to the standard therapy (antihistamines, dezotoksikatsionnaya therapy, topically glucocorticoid-containing ointments), patients with atopic dermatitis are added a preparation of polyoxidonium at a dose of 12 mg intramuscularly every other day, a course of 5 injections. With this method of using the immunomodulator (polyoxidonium), the degree of severity of clinico-laboratory manifestations of secondary immune deficiency decreases due to the complex effect on the functions of macrophages, immunoglobulins and T-cell link (leucocytes, lymphocytes, CD3 + T-lymphocytes and IgA content increased) that Is reflected in a decrease in the clinical manifestations of atopic dermatitis (73% reported remission of symptoms of pathology).

One of the important pathogenetic links in the development of atopic dermatitis is disymunoglobulinemia characterized by an increase in the immunoglobulin content of class E over immunoglobulins of classes M and G [9]. It should be noted that when using polyoxidonium the immunomodulating effects of this drug on the change in the content of these immunoglobulins against the background of treatment have not been revealed [ 7]. In the treatment of atopic dermatitis, it is important to achieve and reduce the level of immunoglobulin class E or the balance of production of immunoglobulins of different classes, and consequently, to reduce the pathogenetic value of immunoglobulin class E, which ultimately affects the significant decrease in clinical manifestations of atopic dermatitis.

The object of the invention is to improve the efficacy of the treatment of atopic dermatitis.

The invention is based on the development of a method for treating atopic dermatitis, wherein the therapeutic efficacy is enhanced by affecting the altered immune system characteristics characteristic of secondary immune deficiency.

This is achieved through the use, along with standard therapy (antihistamines, detoxification therapy, glucocorticoid-containing ointments) immunomodulating substance - the hormone of the epiphysis melatonin. The method consists in the use of the hormone epiphyses melatonin (synthetic analogue of melatonin epiphyseal hormone Melaxen, Melavit Inc., Rockville, USA) at a dose of 3 mg orally at 21.00. Hour for 21 days in combination with standard therapy drugs. Melatonin is a hormone of the epiphysis, it has a wide spectrum of biological activity, including its effects associated with influence on the functions of the immune system [3, 16]. Receptors to melatonin are found on most cells of the immune system, including phagocytes and T-lymphocytes, so its effects are associated with immunomodulation of various parts of the immune system [16, 17].

In the claimed method of treatment, due to the immunomodulatory effect of the melatonin epiphyseal hormone on various subpopulations of immunocompetent cells, including T-lymphocytes, macrophages, etc., the production of immune cells is redistributed towards the predominance of the T-lymphocyte subpopulation and, accordingly, the quantity and functional activity of the humoral immune cells System, including, the level of immunoglobulins, especially immunoglobulin class E.

This method of treating atopic dermatitis allows, due to the direct and indirect influence of the melatonin epiphyseal hormone on the function of immunocompetent cells, to provide an immunomodulating effect. One of the mechanisms of indirect effect of the melatonin epiphyseal hormone on cells of the immune system is its ability to change the functional activity of the hypothalamus and pituitary gland, which in turn causes a fluctuation in the production of various hormones to which receptors on immunocompetent cells, which transforms the activity of the cells of the immune system to predominance T-cell immunity [3]. The direct action of the melatonin epiphyseal hormone on the function of immune cells is associated with the existence of melatonin receptors on T-lymphocytes, macrophages, thymic cells [14], activation of which can lead to an increase in the number of T-lymphocytes and, accordingly, activation of the T-cell functions of the immune system, which Reduces the activity of the humoral link [16] and, accordingly, reduces the production of immunoglobulins of class E, which is directly related to a decrease in the degree of manifestation of secondary immune deficiency and clinical manifestations of allergic skin lesions.

The clinical and immunological efficacy of melatonin is associated with the predominant activation of the Th1 type, since Th2 lymphocytes have no receptors for melatonin [14]. It is known that atopic dermatitis activates Th2 cells and increases the production of cytokines: IL-4, IL-5, IL-13 [1]. IL-5 promotes the maturation of eosinophils and their activation. IL-4 / IL-13 induce B cells to IgE synthesis [1]. Therefore, from the immunological position, the cause of the allergic process, if not the main, then very significant, is the increased activity of Th2 cells. Hence, it becomes evident that one of the directions in immunomodulatory therapy of these processes is the use of drugs that reduce the activity of Th2- and increase the activity of Th1 cells, i.e. Immunomodulators. Since melatonin has stimulating effects on Th1 lymphocytes [15], hence the decrease in IgE and greater clinical efficacy compared with the use of polyoxidonium.

With this method of treatment, the use of the melatonin preparation is more physiological than the use of the immunomodulator polyoxidonium, since the hormone of the epiphysis melatonin is part of the natural neurohormonal chain. This method of treatment makes it possible to treat patients with atopic dermatitis not only with pronounced itching and skin manifestations, pyoderma adhesion and a decrease in the functions of the immune system, but also with less clinical signs of the disease, in which there is no bacterial skin damage, but there are laboratory manifestations of immune deficiency accompanied by A decrease in a number of indicators of the functions of the immune system, this method of treatment makes it possible to use melatonin at all degrees of severity of patients with a decrease in a number of immune system indicators in combination with clinical manifestations of bacterial infection of the skin and without them. It should be noted that the use of melatonin is a cheaper method of treating patients with atopic dermatitis in comparison with the use of the preparation of polyoxidonium.

In addition, patients with atopic dermatitis showed a decrease in melatonin content in comparison with the normative values ​​[18], which indicates a violation of its normal physiological production in this type of pathology, which may be yet another indication for the appointment of melatonin.

The use of polyoxidonium in the treatment of atopic dermatitis has shown its effectiveness in correcting laboratory and clinical manifestations of allergic skin lesions, 5 but the results obtained by us on the use of melatonin in patients with atopic dermatitis with signs of secondary immune deficiency testify to its greater clinical and immunological efficacy in comparison with A preparation of polyoxidonium. Thus, it has been shown that the use of polyoxidonium in the treatment of patients with atopic dermatitis in combination with the symptoms of immune deficiency is accompanied by an increase in the relative content of CD3 + T (by 10% from 66 to 73%) and absolute (by 20% from 1190 to 1430 thousand in mm) Lymphocytes, an increase in the level of IgA and the content of leukocytes (thereby, phagocytic activity) [4]. In our study, against the background of the use of melatonin, the total lymphocyte count increases by 52% (from 1766 to 2700 thousand in mm ³ ), the CD8 + T-lymphocyte content by 27% (from 30.3 to 38.7%), the functional activity of monocytes increases by 11 (By the test of Fc-dependent phagocytosis with monocytes from 60.7 to 67.8%) and granulocytes by 18% (by the test of Fc-dependent phagocytosis by granulocytes from 65.4 to 77.5%), the functional activity of the delayed type hypersensitivity effectors increased by 27% (according to the inhibition index test Migration from 0.56 to 0.41), the content of M-class immunoglobulin increased by 68% (from 1.6 to 2.7 g / l), the content of immunoglobulin class E decreased by 24% (from 442 to 340 IU / ml), along with a decrease in the clinical severity of pyoderma In 100% of patients who had these clinical manifestations of secondary immune deficiency. Clinical efficacy in the use of melatonin and higher by 8% (81%) than with the use of polyoxidonium (73%). Thus, the inclusion of melatonin in the complex treatment of patients with atopic dermatitis is characterized by greater clinical and immunological efficacy in comparison with the preparation of polyoxidonium: the use of melatonin is characterized by clinical efficacy in 81% of patients and does not reduce the manifestation of secondary immune deficiency in 90% of patients.

This method of treating atopic dermatitis has been tested in clinical settings. Clinical trials were conducted on the basis of the Department of Allergology of the Clinic of Immunopathology at the Research Institute of Clinical Research of the Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk. It was used to treat patients with atopic dermatitis.

26 patients with atopic dermatitis were examined, the mean age was 24.3 ± 2.4 years.

Inclusion criteria: 1) age not older than 28 years; 2) absence of clinical and laboratory manifestations of parasitic infection; 3) absence of organic diseases of the nervous and endocrine systems; 4) the lack of taking vegetotrophic, psychocorrecting drugs and systemic glucocorticoids during the previous 3 months. Exclusion criteria: 1) the presence of clinical signs of any physical pathology, except for the underlying disease.

The research methods used to determine the clinical and immunological efficacy of the hormone epithelial hormone melatonin include:

Clinical characteristics of atopic dermatitis according to SCORAD scale [11]: A) prevalence of the process (%), B) intensity of manifestations, including erythema, edema / papule formation, mocculation / cortex, excoriation, lichenization, dryness (expressed in points from 0-3); C) subjective symptoms: itching and loss of sleep (expressed in points from 0 to 10). The degree of severity and was assessed by the number of relapses per year, the average duration of relapse, the prevalence of skin lesion [2].

Evaluation of the immune status included the definition of subpopulation of T and B lymphocytes, immunoglobulins, phagocytic activity of monocytes and peripheral blood neutrophils (MnPK). Identification of lymphocyte populations was performed using monoclonal antibodies (CD3 +, CD4 +, CD8 +, CD16 +, CD20 +), quantitative counting was performed on the FACSCalibur immunocytometer (Becton Dickinson, USA). The immunoregulatory index (IRI) was calculated as the ratio of CD4 + / CD8 + to lymphocytes. A study of the production of hydrogen peroxide by phagocytes was carried out in 96-well plates for enzyme immunoassay. The stimulation of the production of hydrogen peroxide was expressed as an indicator of activation of neutrophils (PAN) in samples with leukocytes and the activation index of monocytes (AMP) in samples with mononuclear cells using the IFA-reader Multiscan MS (Labsystems, Finland). Function MnNPK and assessed by phagocytosis erythrocyte-associated (EA) -complexes. Activity of hypersensitivity cells of delayed type (HRT) -effective cells under conditions of stimulation of cell migration by a suboptimal dose of mitogen (phytohemagglutinin (PHA)) was taken into account as the migration index (MI), migration inhibition by the optimal dose of mitogen (PHA) was taken into account as the migration inhibition index (IMI) , The integral activity of HRT-effectors was considered as an indicator of effector functions (PEF) [4]. The concentration of IgA, IgM, IgG, IgE serum immunoglobulins was determined by rapid nephelometry on an immunochemical analyzer (ISC 2, Beckman, USA).

Statistical analysis was carried out using standard methods, to compare the average values, the Wilcoxon test was used, between the frequency characteristics using the Pearson test ( c ² ).

Intervention. The subjects were randomized to receive: 1) a melatonin preparation (Melatonx, Melavit Inc., Rockville, USA) in combination with standard therapy; 2) standard therapy (antihistamines (Ketotifen 0.001 for 1 tb 2 r.d.), adsorption therapy (Polyphepan 1 tbsp 3 r.d.), external glucocorticosteroid treatment (Celestoderm Cream) .Treatment courses were conducted Within three weeks.

Evaluation of the effectiveness of therapy was conducted 21 days after the time of enrollment. The analysis of the results was carried out taking into account the fact that all subjects received the prescribed treatment. As a result of randomization, two groups of patients with AD were comparable in terms of demographic, immunological parameters and severity of clinical manifestations of the disease.

It should be noted that in the group of subjects examined in 100% of cases, laboratory signs of immune deficiency were revealed, characterized by a decrease in the content and functional properties of peripheral blood T- and B-lymphocyte subpopulations, phagocytic cells, relative to reference values ​​and the presence of 45% In the form of pyoderma.

The effectiveness of melatonin in the correction of manifestations of secondary immune deficiency and clinical signs of atopic dermatitis is presented in Tables 1, 2, and 3.

It is established (Table 1) that the use of melatonin in patients with atopic dermatitis is characterized by immunomodulating activity. Thus, after the course of melatonin use, the total lymphocyte count increases by 52% (from 1766.5 ± 184.2 to 2700.7 ± 131.4 thousand in mm ³ ) (p <0.05), the CD8 + T-lymphocyte content by 27% (from 30.3 ± 2.4 Up to 38.7 ± 1.45) (p <0.05), the content of immunoglobulin class M by 70% (from 1.6 ± 0.04 to 2.73 ± 0.2 g / l), the monocyte phagocytic activity increases by 10% (from 60.7 ± 2.4 to 67.2 ± 1.2%) (P <0.05) and granulocytes by 18% (from 65.4 ± 1.9 to 77.5 ± 1.8%) (p <0.05) along with a decrease in the immunoregulatory index by 27% (from 1.5 ± 0.11 to 1.1 ± 0.05) (p <0.05), The index of inhibition of migration of peripheral blood mononuclear cells in response to phytohemaagglutinin by 28% (from 0.56 ± 0.02 to 0.41 ± 0.02) (p <0.05) and a decrease in the level of immunoglobulin of class E by 24% from 442 IU / ml to 340 IU / ml (p < 0.05).

At the same time, in patients in the control group, the CD20 + B-lymphocyte count increases by 45% (from 11.5 ± 1.3 to 16.7 ± 1.0%, p <0.05), functional activity of peripheral blood monocytes by 11% (from 59.0 ± 1.5 to 65.5 ± 1.3, p <0.05). Thus, in patients receiving melatonin, in comparison with patients who did not use the drug, there is an immunostimulating effect on the function of T-lymphocytes and the phagocytic unit of peripheral blood, along with a decrease in the level of immunoglobulin class E. Patients treated with a standard puncture of therapy have an effect on B -cellular link and functional activity of peripheral blood monocytes.

It should be noted that the frequency of patients who have decreased indices of the functions of the immune system decreases significantly in the group treated with melatonin (Table 2) from 100% to 18% (p <0.05).

The use of melatonin in patients with atopic dermatitis and is characterized by a positive clinical efficacy (Table 3).

In patients with atopic dermatitis, the dynamics of treatment with melatonin undergoes significant changes (6-fold) in the clinical manifestations of allergic skin lesions on the SCORAD scale (by 87%), in the control group and positive changes are noted - the SCORAD index decreases by 69% (from 44.7 ± 2.9 to 18.7 ± 3.1). Thus, in the group receiving standard therapy with inclusion of the melatonin preparation, a significantly greater decrease in the severity of clinical manifestations of atopic dermatitis was observed in 18% (82% in the experimental comparison with 64% in the control group). The effectiveness of the inclusion of melatonin in the complex treatment of patients with atopic dermatitis is characterized by clinical efficacy in 81% of patients and a decrease in signs of secondary immune deficiency in 90% of patients treated.

Below are the results that explain this method of treating atopic dermatitis.

Example 1 . Patient M., 22. Diagnosis: atopic dermatitis, generalized form, stage of exacerbation. On admission, she complained of skin itching, burning and soreness of the skin, extensive erythematous skin rashes, dry skin, scaling of the skin, thickening of the skin, crusts and pustular rashes on the skin. Suffers from atopic dermatitis from the first year of life. The course of the disease is year-round with exacerbations in the autumn-winter period. Skin itching intensifies against the background of psychoemotional disorders, eating eggs, chocolate. The severity of clinical manifestations on the SCORAD scale was 38 points. According to the immunogram: lymphocyte count in mm ³ - 1225 thousand (1120-3210 mm ³ ), CD3 + T-lymphocytes - 65% (58-83%), CD4 + T-lymphocytes - 35% (29-59%) , CD8 + T-lymphocytes - 29% (17-40%), IRI - 1.21 (0.9-2.8), CD20 + B-lymphocytes - 12% (8-17%), CD16 + HK cells - 12% (6- 24%), Fc-phagocytosis of granulocytes - 65% (59-89%), Fc-phagocytosis of monocytes - 61% (52-73%), migration index of PHA - 1.32 ye (min-0.8 cu), inhibition index Migration FGA - 0.54 cu (Max - 0.5 cu), the indicator of effector functions is 2.45 cu. (Min - 2.1 cu), IgM - 1.2 g / l (0.7-3.0 g / l), IgA - 4.3 g / l (0.5-2.5 g / l), IgG - 11.4 g / l (6.1-12.9 G / l), PAM - 1.8 (1.8-7.1), PAN - 4.2 (2.0-7.0), IgE - 160 IU / ml (160-210 IU / ml). Signs of secondary immune deficiency in the form of a decrease in the functional activity of delayed-type hypersensitivity effectors in terms of the index of migration of PHA, the index of inhibition of migration of PHA, the index of effector functions (T-cell insufficiency). The patient was treated with standard therapy with antihistamine drugs (Ketotifen 0.001 for 1 TB 2 r.d.), adsorption therapy (Polyphepan 1 tbsp 3 r.d.), external glucocorticosteroid treatment (Celestoderm cream) with the inclusion of synthetic Analogue of the melatonin epidermal hormone "Melatonx" 3 mg at 21.00 ("Melavit", USA). After the course of therapy for 21 days, there was a significant improvement in the patient's condition: skin itching decreased, skin rashes significantly decreased and did not recur, pustular rash disappeared, sleep normalized. The severity of clinical manifestations on the SCORAD scale was 6 points (decreased by 85%). According to the control immunogram: lymphocyte count in mm ³ - 1412 thousand (1120-3210 mm ³ ), CD3 + T-lymphocytes - 70% (58-83%), CD4 + T-lymphocytes - 44% (29-59% ), CD8 + - 21% (17-40%), IRI - 2.1 (0.9-2.8), CD20 + B-lymphocytes - 11% (8-17%), CD16 + NK cells - 11% (6-24%), Fc-phagocytosis of granulocytes - 81% (59-89%), Fc-phagocytosis of monocytes - 96% (52-73%), migration index of PHA - 1.2 cu (Min - 0.8 ye), the migration inhibition index of PHA is 0.45 USD. (Max - 0.5 cu), the indicator of effector functions is 2.7 cu. (Min - 2.1 ye), IgM - 1.75 g / l (0.7-3.0 g / l), IgA - 2.2 g / l (0.5-2.5 g / l), IgG - 10.6 g / l (6.1-12.9 g / l ), PAM - 1.9 USD. (1.8-7.1 cu), PAN - 4.4 cu (2.0-7.0 cu), IgE - 145 IU / ml (160-210 IU / ml). After treatment, the total lymphocyte counts underwent positive changes by 15% (from 1225 thousand to 1412 thousand mm ³ ), CD3 + T-lymphocytes by 8% (from 65 to 70%), CD4 + T-lymphocytes by 25% ( From 35 to 44%), Fc-phagocytosis of granulocytes by 7% (65 to 81%) and monocytes by 57% (from 61 to 96%), IM PHA by 10% (from 1.32 to 1.2), the IgM content increased by 45% % (From 1.2 to 1.75 g / l), the IgA content was normalized by 51% (from 4.3 to 2.2), the IgE content decreased by 10% (from 160 to 145 IU / ml), which indicates immunomodulatory effects of melatonin on the immune system , Characterizing the T-cell link, the functional activity of macrophages, the content of immunoglobulins, including a decrease in IgE. The patient was discharged from the department in a satisfactory condition with an improvement in clinical status.

Example 2 . Patient N., 17 years old. Diagnosis: atopic dermatitis, generalized form, stage of exacerbation. On admission, she complained of skin rashes, itchy skin, burning and soreness of the skin, wetness. Suffers from atopic dermatitis from the first year of life. The course of the disease is year-round with exacerbations in the autumn-winter period. Standard protocols for the treatment of the disease does not use, it is treated with Chinese homeopathic preparations, is on a strict protein-free diet. The severity of clinical manifestations on the SCORAD scale was 58 points. According to the immunogram: lymphocyte count in mm ³ - 1581 thousand (1120-3210 thousand in mm ³ ), CD3 + T-lymphocytes - 61% (58-83%), CD4 + T-lymphocytes - 41% (29- 59%), CD8 + - 21% (17-40%), IRI - 1.95 (0.9-2.8), CD20 + B-lymphocytes - 9% (8-17%), CD16 + NK cells - 27% (6-24% ), Fc-phagocytosis of granulocytes - 74% (59-89%), Fc-phagocytosis of monocytes - 63% (52-73%), migration index of PHA - 1.08 ye (min - 0.8 ye), inhibition index of migration of PHA - 0.44 ye (Max-0.5 ye), the effector function index is 2.46 ye (min-2.1 ye), IgM is 1.19 g / l (0.7-3.0 g / l), IgA is 1.8 g / l (0.5-2.5 g / l) IgG - 5.1 g / l (6.1-12.9 g / l), PAM - 2.4 cu. (1.8-7.1 ye), PAN - 7.3 USD. (2.0-7.0 ye), IgE - 135 IU / ml (160-210 IU / ml). Laboratory signs of immune deficiency in the form of a decrease in the functions of the effectors of HRT (T-cell insufficiency) and the content of immunoglobulin class G. The patient was treated with baseline therapy with antihistamines (Ketotifen 0.001 1 TB 2 r.), Adsorption therapy (Polyphepan 1 3 liters per day), external glucocorticosteroid treatment (Celestoderm cream) with the inclusion of a synthetic hormone analogue of melatonin melatonin, 3 mg at 3 pm (Melavit, USA). After the course of therapy for 21 days, there was a significant improvement in the patient's condition: skin itching decreased, at night it did not disturb at all, skin rashes decreased significantly and did not recur, pustular rashes absent, sleep normalized. The severity of clinical manifestations on the SCORAD scale was 8 points (a decrease in expression by 86%). According to the data of the repeated immunogram: lymphocyte count in mm ³ - 3217 thousand (1120-3210 thousand in mm ³ ), CD3 + T-lymphocytes - 67% (58-83%), CD4 + T-lymphocytes - 42% (29 -59%), CD8 + - 27% (17-40%), IRI - 1.56 (0.9-2.8), CD20 + B-lymphocytes - 7% (8-17%), CD16 + NK cells - 17% (6- 24%), Fc-phagocytosis of granulocytes - 59% (59-89%), Fc-phagocytosis of monocytes - 62% (52-73%), migration index of PHA - 1.1 ye (min - 0.8 ye), inhibition index of migration of PHA - 0.37 ye (max - 0.5 ye), the indicator of effector functions is 3 ye (min-2.1 ye), IgM is 2.35 g / l (0.7-3.0 g / l), IgA is 1.15 g / l (0.5-2.5 g / l ), IgG - 6.6 g / l (6.1-12.9 g / l), PAM - 1.8 ye (1.8-7.1 ye), PAN - 2.9 ye (2.0-7.0 ye), IgE - 110 IU / ml (160-210 IU / Ml). The following indicators have undergone positive dynamics: the total lymphocyte count increased 2 times (from 1,581,000 to 3,217,000 mm ³ ), CD3 + lymphocytes by 10% (from 61% to 67%), CD8 + by 28% (from 21% to 27% %), The level with IgM increased by 97% (from 1.19 to 2.35 g / l), IgG by 29% (from 5.1 to 6.6 g / l), the IgE level decreased by 22% (from 135 to 110 IU / ml (160 -210 IU / ml)), the parameters of the immunoregulatory index and the content of NK cells with the CD16 + phenotype stabilized, indicating immunomodulatory effects of melatonin having an effect on the T-cell link, the content of immunoglobulins: an increase in IgG content and a decrease in IgE. The patient was discharged from the department in a satisfactory condition with an improvement in clinical status.

Example 3 . Patient P., 18 years old. Diagnosis: atopic dermatitis, generalized form, stage of exacerbation. At admission, she complained of skin rashes, itchy skin, dry skin, pustular formations, sleep disorders. Suffers from atopic dermatitis from the first year of life. The course of the disease is year-round with exacerbations in the autumn-winter period. In the study of dermographism - its white version. The severity of clinical manifestations on the SCORAD scale was 38 points. According to the immunogram: lymphocyte count in mm ³ - 1805 thousand (1120-3210 thousand in mm ³ ), CD3 + T-lymphocytes - 59% (58-83%), CD4 + T-lymphocytes - 27% (29- 59%), CD8 + - 28% (17-40%), IRI-0.9 (0.9-2.8), CD20 + B-lymphocytes - 6% (8-17%), CD16 + NK cells - 2% (6-24 %), Fc-phagocytosis of granulocytes - 65% (59-89%), Fc-phagocytosis of monocytes - 64% (52-73%), migration index of PHA - 1.0 cu. (Min - 0.8 ye), the inhibition index of migration of PHA is 0.3 USD. (Max - 0.5 cu), the indicator of effector functions is 3.8 cu. (Min - 2.1 ye), IgM - 2.2 g / l (0.7-3.0 g / l), IgA - 0.5 g / l (0.5-2.5 g / l), IgG - 9.1 g / l (6.1-12.9 g / l ), PAM - 2.1 USD. (1.8-7.1 cu), PAN - 2.1 cu (2.0-7.0 cu), IgE - 410 IU / ml (160-210 IU / ml). Laboratory signs of secondary immune deficiency with involvement of the T-cell link are revealed. The patient underwent basal therapy with antihistamine drugs (Ketotifen 0.001 for 1 TB 2 r. In.), Adsorption therapy (Polyphepan 1 tbsp 3 r.d.), external glucocorticosteroid treatment (Celestoderm cream) with the inclusion of synthetic Analogue of the melatonin epidermal hormone "Melatonx" 3 mg at 21.00 ("Melavit", USA). After the course of therapy for 21 days, there was a significant improvement in the patient's condition: skin itching, skin rashes and did not recur, decreased sleep normalized. The severity of clinical manifestations on the SCORAD scale was 8 points (a 79% decrease in severity). According to the data of the repeated immunogram: lymphocyte count in mm ³ - 2849 thousand (1120-3210 thousand in mm ³ ), CD3 + T-lymphocytes - 65% (58-83%), CD4 + T-lymphocytes - 42% (29 -59%), CD8 + - 23% (17-40%), IRI - 1.73 (0.9-2.8), CD20 + B-lymphocytes - 6% (8-17%), CD16 + HK cells - 14% (6-24 %), Fc-phagocytosis of granulocytes - 72% (59-89%), Fc-phagocytosis of monocytes - 69% (52-73%), migration index of PHA - 0.89 ye (min - 0.8 ye), index of inhibition of migration of PHA - 0.2 У.е. (Max - 0.5 cu), the indicator of effector functions is 3.9 cu. (Min - 2.1 cu), IgM - 2.15 g / l (0.7-3.0 g / l), IgA - 0.75 g / l (0.5-2.5 g / l), IgG - 8.9 g / l (6.1-12.9 G / l), PAM - 2.0 (1.8-7.1), PAN - 3.8 (2.0-7.0), IgE - 120 IU / ml (160-210 IU / ml). After treatment, there was a significant decrease in the severity of laboratory manifestations of T-cell immune deficiency along with an increase in phagocytic activity of granulocytes and a decrease in IgE content in the form of an increase in CD3 + T-lymphocyte count by 10% (from 59% to 65%), CD4 + T-lymphocytes By 55% (from 27% to 42%), IRI by 80% (from 0.96-1.73), Fc-phagocytosis of granulocytes by 10% (from 65% to 72%), the index of migration of mononuclear cells of PHA decreased by 11% 1.0 to 0.89), the IgE content was reduced by 71% (from 410 IU / ml to 120 IU / ml). The patient was discharged from the department in a satisfactory condition with an improvement in clinical status.

Thus, the inclusion of melatonin in the course treatment of patients with atopic dermatitis is characterized by clinical efficacy in 81% of cases, with the severity of the clinical manifestations of the disease reduced by 87%, which makes it possible to widely apply this method in clinical practice for the treatment of atopic dermatitis.

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CLAIM

The method of treatment of atopic dermatitis, which consists in the addition of an immunomodulatory medication to standard therapy, including antihistamines, detoxification therapy, local glucocorticoid-containing ointments, characterized in that as an immunomodulating drug, patients are prescribed a melatonin epiphysis hormone at a dose of 3 mg at 21.00 hours Course in 21 days.

print version
Date of publication 01.04.2007гг

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