RU2361604C1 - Way of treatment of atopic dermatitis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: way concerns medicine, namely to dermatology and can be used for treatment of atopic dermatitis. The way includes intramuscular introduction of the thymodepressin preparation daily within 10 days. Thus at mass of a body of the patient less than 75 kg, thymodepressin is administered in a dose of 1 ml, and at mass of a body more than 75 kg - in a dose of 1.5 ml.

EFFECT: possibility to reach clinical improvement at depression of risk of complications and by-effects.

3 ex, 1 tbl

Description

The invention relates to medicine, namely to dermatology, and can be used to treat severe forms of atopic dermatitis that are torpid to traditional therapy.

Improving the treatment of atopic dermatitis (AD) remains an important medical and social problem, which is associated with a persistently high incidence of dermatosis in the Russian Federation, a chronic recurrent course of the disease and the complexity of the therapy. In recent years, patients with AD noted torpidity of the course, inefficiency of standard therapeutic approaches, early disability (Kungurov N.V. Atopic dermatitis. Types of course, treatment principles / N.V. Kungurov, N.M. Gerasimova, M.M. Kokhan. Yekaterinburg, 2000. - 272 p .; II Balabolkin. The modern concept of pathogenesis and principles of treatment of allergic diseases in children / II Balabolkin // Pediatrics. - 2003. - No. 4. - P.52-57; Schultz- Larsen F. Epidemiology of atopic dermatitis / F. Schultz-Larsen, JM Hanifin // Immunol. Allergy Clin. North Am. - 2002. - Vol.22. - P.1-24).

AD is a multifactorial, polygenic skin disease, in the pathogenesis of which genetic determination is established, as well as a dysfunction of the immune system with hyperproduction of class E immunoglobulin, a violation of cytokine regulation and the ratio of helper lymphocytes of the first and second order, deficiency of suppressor T-lymphocytes, and a violation of apoptosis processes, which is realized both at the systemic and local levels in the skin (Akdis M. Cytokine network and dysregulated apoptosis in atopic dermatitis / M. Akdis [et al] // Acta Odontol Scand. - 2001 Jun. - Vol. 59 (3) - P .178-82; Schön MP, Ludwig RJ Lymphocyte trafficking to i nflamed skin - molecular mechanisms and implications for therapeutic target molecules // Ann. Derm. - 2005. - Vol. 9 - No. 2, - P.225-243).

To achieve consistency in the methods for assessing the severity of the course of blood pressure and the effectiveness of the therapy, as well as to use statistical methods to analyze the results, it was decided to determine (calculate) the complex severity indices SCORAD and EASI with the development of all components of these indices.

The SCORAD index was determined by a formula that comprehensively took into account the prevalence of skin rashes, their morphology, the severity of manifestations and the severity of the patient's subjective sensations. The EASI index was determined according to the generally accepted methodology, where the doctor evaluated the disease according to its main manifestations (E - erythema; I - infiltration; Ex - excoriation; L - lichenification), that is, the intensity of the symptoms of blood pressure was recorded. Symptoms were evaluated separately in 4 locations: upper limbs (A), lower limbs (B), trunk (C), face and neck (D) using a score of symptom severity from 0 to 3 points.

There is a method of complex treatment of severe forms of blood pressure, carried out mainly by the appointment of systemic corticosteroid hormones and cyclosporin A. (Hijnen DJ, ten Berge O, Timmer-de Mik L, Bruijnzeel-Koomen CA, de Bruin-Weller MS. Efficacy and safety of long-term treatment with cyclosporin A for atopic dermatitis. J Eur Acad Dermatol Venereol. 2007 Jan; 21 (1): 85-9).

Immunosuppressive therapy drugs act primarily on activated T cells, inhibit the release of lymphokines, and thereby inhibit immuno-dependent pathological processes. When using drugs of this group, special precautions must be observed: constant monitoring by a doctor with experience in the use of immunosuppressive therapy and laboratory monitoring are necessary.

An immunosuppressant cyclosporin is recommended as the drug of choice for systemic therapy of severe, therapeutically resistant forms of blood pressure. Its therapeutic efficacy is due to the suppression of the secretion of interleukins and other lymphokines by activated T-lymphocytes, which leads to a decrease in the activity of T-lymphocytes both in the dermal layer and in the epidermis and indirectly affects the state of blood vessels, the hyperproliferation of the epidermis, as well as the activity of inflammatory cells.

This drug is not highly selective and does not always allow for complete remission of the disease, which leads to the need for the appointment of repeated courses of treatment or long-term maintenance therapy. In addition, clear indications for its purpose have not been determined, the choice of the optimal dosage regimen is not sufficiently substantiated.

The disadvantages of this method is the high cost of the drug, rapid relapse after treatment, significant side effects and contraindications.

Closest to the proposed method of treatment, the prototype of the invention is the Cyclosporin administration regimen, which is currently used in dermatological practice. This scheme includes: cyclosporine (initial dose of 2.5 mg / kg per day (or 5 mg / kg per day, if you need a very quick effect). If within 2 weeks of using the drug at a dose of 2.5 mg / kg per day, it is not possible to achieve the desired effect, the daily dose can be quickly increased to a maximum of 5 mg / kg per day. The maximum daily dose of the drug is 5 mg / kg per day. It is advisable to carry out long-term treatment using minimum effective doses. should be reduced gradually, n if severe forms of the disease, it is advisable to use the regimen of intermittent re-therapy with a gradual dose reduction. (Kochergin N.G. Experience in the use of neoral in atopic dermatitis in children. // Ros.kozhn. venere. diseases. - 1998. - No. 2. - S.35-37).

The use of this scheme is associated with the development of side effects and complications: an increase in serum creatinine concentration compared to the initial level; arterial hypertension. During treatment, constant monitoring of laboratory parameters, the value of blood pressure, the state of the liver and kidneys, as well as determination of the concentration of lipids in the blood serum (before treatment and after the first month of treatment) is necessary. During treatment with cyclosporine, at least 2 measurements of serum creatinine are necessary. Before starting therapy and in the first 3 months of treatment, it is necessary to control the level of uric acid in the blood and urine. The use of the drug is possible only in specialized medical institutions, doctors with experience in conducting immunosuppressive therapy.

The objective of the invention is to increase the therapeutic efficacy of the use of the immunosuppressant thymodepressin in the most severe forms of blood pressure (diffuse, continuously recurring blood pressure, erythroderma), prevention of side effects, and prolongation of remission.

The technical result is achieved by the fact that in the method of treating AD with an immunosuppressive drug, thymodepressin is used as the latter by intramuscular injection in solution in a therapeutic dose of 1.0-1.5 ml daily for 10 days.

The essence of the invention is to optimize the appointment of thymodepressin based on the study of its effect on clinical parameters and the absence of complications.

Timodepressin is a synthetic peptide preparation consisting of D-amino acid residues of glutamic acid and tryptophan. The drug was approved by the Pharmaceutical Committee of the Ministry of Health of the Russian Federation for medical use in 2000. It has an immunosuppressive effect, inhibits the reactions of humoral and cellular immunity. At the cellular level, thymodepressin has a suppressive effect on the absolute content of peripheral blood lymphocytes, causing a proportional decrease in both helper cells and suppressors.

The great advantage of thymodepressin as an immunosuppressor is the absence of toxicity. In toxicological studies of thymodepressin, no side effects of the drug, toxic and allergic reactions were noted with a thousand-fold increase in the therapeutic dose.

The appointment of thymodepressin in the treatment of severe forms of blood pressure will significantly increase the effectiveness of treatment, reduce the frequency of complications from the therapy.

The appointment of thymodepressin as part of the treatment of severe forms of blood pressure by intramuscular injection in solution at a therapeutic dose of 1.0-1.5 ml / kg daily for 10 days can significantly increase the effectiveness of treatment and reduce the incidence of complications from immunosuppressive therapy.

The duration of treatment is determined by the fact that the use of the drug for less than 10 days does not allow to achieve a stable therapeutic effect, since a stable therapeutic effect can be achieved within the specified time, which is confirmed by clinical and laboratory data. The daily dose (1.0-1.5 ml) is determined by the clinical form, the nature of the course of blood pressure, the timing of the therapeutic effect, and the absence of adverse reactions to the drug.

The method is as follows.

Patients on the background of symptomatic therapy (antihistamines, enterosorbents, external ointment treatment) are prescribed thymodepressin in the form of intramuscular injections. Thymodepressin is prescribed in a solution for intramuscular injection in a therapeutic dose of 1.0 ml of a 0.1% solution (with a patient's body weight of more than 75 kg - 1.5 ml of solution) daily for 10 days, with a regression of clinical manifestations of less than 50%, a second course is carried out treatment in the form of intramuscular injection of a 0.1% solution in a therapeutic dose of 1.0 ml (with a patient's body weight of more than 75 kg - 1.5 ml of solution) daily for 10 days.

When evaluating the clinical effectiveness of a new method of treating blood pressure, the following criteria were taken into account: 1) a change in subjective sensations (disappearance or reduction of skin itching, burning) 2) the dynamics of objective clinical manifestations (based on changes in SCORAD and EASI indices); 3) general condition (temperature, blood pressure, pulse, clinical and biochemical analyzes of blood, urine).

The use of the proposed method of therapy is illustrated by the following examples.

Example 1

Patient K., aged 30 years. Was admitted to the hospital with complaints of rashes on the skin of the trunk and limbs, accompanied by itching, restless sleep. The girl was born from young parents, the mother of the child suffers from blood pressure (a common form), her grandmother on the mother's side has bronchial asthma. The girl’s father considers himself healthy.

The first manifestations of blood pressure were noted at the age of three months after the introduction of carrot juice and were manifested in the form of hyperemia and peeling of the skin of the cheeks, buttocks, and were accompanied by mild skin itching. It is registered with a dermatologist, against the background of the treatment prescribed by the dermatologist, periods of unstable remission were noted. From 13 years old - the skin process has become widespread with localization in the upper and lower extremities, trunk, face and neck in the form of foci of hyperemia and infiltration. Over the last year - remissions of the skin process were not observed.

When examining a patient, the skin process is widespread, represented by foci of hyperemia, skin infiltration, an abundance of excoriations in the face, neck, décolleté, back, upper limbs, hips, knee bends, an abundance of excoriations, serous-hemorrhagic crusts. When assessing the severity of clinical manifestations, the SCORAD index before treatment was 64 points, the EASI index was 39.3 points, the dermatological index of quality of life (DIC) was 23, and the clinical score for pruritus was 7 points.

During a clinical and laboratory study in the hospital of the Federal State Institution of UrNIIDViI of the Russian Medical Technologies, deviations from the norm of peripheral blood - eosinophilia up to 7% were found. The patient was prescribed intramuscular injection of timodepressin at a dose of 1.0 ml per day for 10 injections per treatment course. Against the background of the treatment, by the 3rd day of therapy there was a decrease in the intensity of skin itching, a decrease in hyperemia and skin infiltration. After the treatment, the patient was discharged from the hospital in a state of remission of the skin process. After the end of therapy, the SCORAD index was 39.3 points, the EASI index was 4.2 points, the dermatological index of quality of life (DIC) was 3, and the clinical score for pruritus was 0 points.

Example 2

Patient I., 21 years old, has been under observation in the clinic since 15 years old with a diagnosis of blood pressure, diffuse form. Repeatedly underwent inpatient treatment, including desensitizing, detoxification, systemic (prednisone 30 mg / day) and external corticosteroid therapy, was prescribed with improvement. The skin process has become resistant to the therapy, frequent exacerbations combined with short periods of remission. When assessing the severity of clinical manifestations, the SCORAD index before treatment was 84.5 points, the EASI index was 44.6 points, the dermatological quality of life index (DIC) was 25, and the clinical score for pruritus was 10 points.

The patient was prescribed thymodepressin in the form of intramuscular injections at a dose of 1.0 ml, 10 injections per course. Two courses of injections were carried out with an interval of 7 days.

As a result of the therapy, from 4-5 days of treatment, there was a decrease in the intensity of skin itching and a decrease in hyperemia, from the 8th day of skin infiltration and peeling, by the end of thymodepressin therapy, only foci of moderate lichenification and dry skin remained, which regressed by the 4th week of observation. After the end of therapy, the SCORAD index was 7.4 points, the EASI index was 0.3 points, the dermatological index of quality of life (DIC) was 0, and the clinical score for pruritus was 0 points.

Example 3

Patient E., 27 years old, has repeatedly received inpatient treatment courses at the clinic of the Federal State Institution of UrNIIDViI of the Russian Medical Technologies. Sick from an early childhood, was registered with a dermatologist, was disabled on the skin process up to 16 years. The skin process was common. The patient repeatedly received courses of systemic corticosteroids, antihistamines, courses of heparin therapy.

The exacerbation of the skin process over the past year is associated with pregnancy and the birth of a child.

At the time of going to the clinic, the rashes were diffuse, accompanied by excruciating itching. When assessing the severity of clinical manifestations, the SCORAD index before treatment was 86 points, the EASI index was 42.6 points, the dermatological index of quality of life (DIC) was 25, and the clinical score for pruritus was 9 points.

The patient was prescribed thymodepressin in the form of intramuscular injections of a 0.1% solution at a dose of 1.5 ml, 10 injections per course. Two courses of injections were carried out with an interval of 7 days.

As a result of the therapy, from the 7th day of treatment there was a decrease in the intensity of skin itching, a decrease in hyperemia and skin infiltration, from the 10th day - skin infiltration and peeling, and from the 10th day of treatment, external glucocorticosteroids were canceled and indifferent ointments and creams were prescribed. After completing the course of treatment with thymodepressin, only foci of moderate lichenification and dry skin were preserved, which regressed by the 4th week of observation. After completion of therapy, the SCORAD index was 5.3 points, the EASI index was 0.4 points, the dermatological index of quality of life was 0, and the clinical score for pruritus was 0 points.

The proposed method in the Federal State Institution of UrNIIDVi and Rosmedtehnologii treated 10 AD patients aged 15 to 30 years, including 4 women and 6 men. The duration of the disease ranged from 15 to 30 years. Previously, patients were treated with antihistamines, detoxification therapy, systemic and topical corticosteroids, which did not allow for complete clinical remission. After a course of thymodepressin, a clinical improvement was achieved in 10 out of 10 patients (100%). The duration of remission ranged from 5 months to 1 year.

Comparative data of the invention and prototype are shown in the table.

Table The proposed method Known method 1.Duration of treatment, weeks 1-2 weeks 4-5 weeks 2. Treatment efficiency: - clinical recovery 24.0% 3.0% - significant improvement 72.0% 14.0% - improvement 4.0% 83.0% 3. The duration of the remission period 8-9 months 1-2 months 4. Side effects are absent toxic-allergic (data from the Federal State Institution UrNIIDViI Rosmedtekhnologii) toxic, mutagenic (authors)

The table shows the own data from studies of the clinical effectiveness of the proposed method for the treatment of blood pressure. Obviously, the effect of the treatment was obtained in all (100%) patients, clinical remission was achieved in 30% of cases, a significant improvement in 70%.

Thus, a new, gentle method for the treatment of blood pressure was tested, including the administration of an immunosuppressive drug, which allowed to significantly increase the effectiveness of therapy while reducing the risk of systemic complications, and to increase the duration of clinical remission.

Claims (1)

A method of treating atopic dermatitis, including intramuscular administration of the drug thymodepressin daily for 10 days, characterized in that when the patient weighs up to 75 kg, thymodepressin is administered in a therapeutic dose of 1 ml, and with a body weight of more than 75 kg - 1.5 ml.