RU2343914C1 - Method of treatment of atopic dermatitis (versions) - Google Patents

Abstract

FIELD: medicine; dermatology.

SUBSTANCE: in one method, the tilorone is enterd under the scheme: 1st day - 0.250 g, 2nd day - 0.125 g and further in three days on 0.125 g within 5 weeks. In three months enter tilorone on 0.125 g every third day 10 more times irrespective of clinical implications. In other way in addition with the treatment specified above simultaneously locally apply compresses with a sorbent, perphtorane and mineral water in the ratio 1:1:2-3.

EFFECT: increase of efficiency of treatment at the expense of normalisation clinico-immunologic indicators, improvement of microbiocenosis of integuments.

2 cl, 3 ex, 6 tbl

Description

The group of inventions relates to medicine, in particular to immunology-allergology, and can be used to treat atopic dermatitis.

Patients with atopic dermatitis (A.D.) suffer not only from the presence of rashes, itching, excoriation, but also have a significant decrease in physical activity, restrictions in social and professional life (I. Balabolkin. Allergic diseases in children. M .: Medicine, 1998, - 268 pp., Revyakina V.A., Atopic dermatitis in children, Diss. Dr. med. Sciences. M., 1993, p. 263).

The frequency of severe AD forms associated with the bacterial and fungal flora (Allergic diseases. Diagnosis and treatment. Practical manual under the editorship of R. Patterson. Per. From English M., 2000) has significantly increased (up to 31%). .). The skin is no longer considered only as a barrier organ that protects the internal environment of the body. It also performs an important function in the body's immune defense system, in the elimination of toxins, in thermoregulation, etc.

It is known that allergic diseases are accompanied by various changes on the part of the body's immune system. There is overproduction of immunoglobulin E, an increased concentration of IL-4 and a decrease in interferon-gamma (GI Menemchiadis, “The Importance of Chronic Enterovirus Infection in the Development of Allergic Diseases in Children" - abstract of a dissertation, candidate of medical sciences, M.1987, p. 23). The enhanced release of histamine from mast cells and basophils also underlies the pathogenesis of A.D. In addition, mediators such as kinins, leukotrienes, prostaglandins, and neuropeptides play a role in the formation of pruritus.

Treatment A.D. should be complex, individual and depend on the form and stage of the disease.

General principles of treatment A.D. include:

diet therapy, elimination regimen, systemic pharmacotherapy, external (local) therapy, rehabilitation and educational programs. With exacerbations of A.D. prescribe systemic and local glucocorticosteroids (Algorithms for diagnosis and treatment. Immunology and allergology. M., publishing house "GEOTAR-Med", 2003, S. 37-43).

Systemic pharmacotherapy includes the use of antihistamines and / or stabilizer of membrane cells, in severe cases, antibacterial drugs and glucocorticosteroids.

However, the duration of remission after completing the course of treatment remains not long, which makes us look for new methods of therapy.

In the work of Dimieva G.M. ("Peculiarities of the cytokine and immunocomplex mechanisms of regulation of IgE content in patients with atopic dermatitis", abstract of diss. Candidate of medical sciences - M. - 1999. - 24 pp.) In children who participated in the study, skin colonization was revealed only S. aureus and for the correction of disorders in interferon status, amixin was prescribed at a dose of 0.06 g daily for 2 days, then once every three days for only 5 weeks (0.6 g per course).

The author of this work noted that in the complex treatment of atopic dermatitis in children, neither a general therapeutic effect nor an individual therapeutic effect was revealed in comparison with a group of patients not receiving amixin.

However, upon further observation, it was found that patients receiving amixin formed a longer remission (with amixin - 9.9 ± 1.7 months and without amixin - 5.3 ± 1.1 months).

The proposed method for the treatment of atopic dermatitis is as follows: apply tilorone according to the scheme: 1st day - 0.250 g, 2nd day - 0.125 g and then after three days 0.125 g for 5 weeks, three months later, 0.125 g of tiloron is administered Once a day every three days another 10 times, regardless of clinical manifestations.

The total dose for the entire course is at least 2.5 g.

Tiloron (synonyms: amixin, levomax) refers to the oral inducers of endogenous interferon. However, studies of recent years have shown a wider spectrum of action of tilorone, such as antiviral, immunomodulating, antitumor, antimicrobial, enzymatic and radioprotective (Ershova F.I. et al., Kavetsky R.E. et al., Bogatsky A.V. et al. ., Kruger RF et al., Megel H. et al., Cleng JH et al., Levy L., Lullmann-Rauch R., Regelson W., Talas M.). The diversity of the biological activity of tilorone gives reason to include it in the program of complex therapy A.D. in adult patients.

Data on longer remission (with amixin - 9.9 ± 1.7 months and without amixin - 5.3 ± 1.1 months) in patients treated with amixin (Dimieva G.M. Features of the cytokine and immunocomplex mechanisms of regulation of IgE content in patients with atopic dermatitis. Author's abstract. Diss. Candidate of Medical Sciences - M. - 1999. - 24 pp.), prove the need for a second course of amixin (tilorone).

In addition, the proposed method for the treatment of atopic dermatitis is as follows: apply tilorone according to the scheme: 1st day - 0.250 g, 2nd day - 0.125 g and then three days later 0.125 g for 5 weeks, three months later, tiloron is administered 0.125 g once a day every three days another 10 times regardless of clinical manifestations using compresses locally, while using compresses with sorbent, perfluorane and any mineral water in the ratio: 1 part sorbent, 1 part perftoran in 2-3 parts warm mineral water.

As the sorbent, for example, enterosgel or peccek can be used.

After hygiene procedures, compresses are applied to the affected area of the skin based on 10-15 square centimeters of the area according to the scheme - two days in a row, then after 2-3 days another 3-4 times.

Enterosgel is an organosilicon enterosorbent.

Peccecom - pectic acid (from beet pulp).

Pharmacological action of peccome: a dietary supplement that stimulates the functioning of the gastrointestinal tract.

Perftoran - submicron (0.05-0.15 microns) 10% emulsion (white with a bluish tint) based on organo perfluoro compounds - 19.5 g; proxanol-268 - 4 g, sodium chloride - 0.6 g, potassium chloride - 0.039 g, magnesium chloride - 0.019 g, sodium bicarbonate - 0.065 g, sodium hydrogen phosphate - 0.02 g and glucose - 0.2 g;

The pharmacological effect of perfluorane is gas transport, plasma substituting, detoxifying, membrane stabilizing, cardioprotective, diuretic, anti-shock. Blocks calcium channels. It is capable of reversibly (by analogy with hemoglobin) to bind and transport oxygen, carbon dioxide (pharmabook.net 2006).

The compress mixture is infused for 20-30 minutes to form a gel suspension and imposed according to generally accepted rules.

This procedure allows you to remove destroyed cells, proinflammatory cytokines and other products of inflammation from the focus of inflammation and provide more favorable conditions for exposure to therapeutic ointments.

Under dynamic monitoring were 85 patients with a verified diagnosis of A. D. aged 16 to 48 years. There were 59 women, 26 men.

The average age was 20.7 ± 3.6 years. The duration of the disease is 14.8 ± 4.2 years.

All patients underwent clinical, immunological, allergological and microbiological examination.

Conducted a study of the level of immunoglobulins of classes A, M, G by the method of simple radial immunodiffusion according to Mancini. The level of total IgE, cytokines (IL-4, IL-8, INF-y) - by enzyme-linked immunosorbent assay (ELISA).

We studied the levels of populations and subpopulations of peripheral blood lymphocytes - CD3 + (T-lymphocytes), 3F3 (B-lymphocytes), CD4 + (T-helpers / inducers), CD8 + (T-killers) using monoclonal antibodies (MedBioSpektr, Moscow), functional activity granulocytes in the test with nitrosine tetrazolium and phagocytic ability against latex with phagocytic count and zymosan-induced neutrophil chemiluminescence (BV Pinegin et al. Methodological recommendations for immunological studies. 1996), also took into account the total number of lake Oocytes and their formula.

Microbiocenosis of the skin was studied by the standard microbiological method with the calculation of colony forming units per dm ² (CFU / dm ² ).

Statistical processing was carried out using computer programs "Statistica".

A widespread rash was observed in 56.4% of patients, intense rashes and prolonged itching were noted in 22.3% of patients, intestinal dysfunction in 89.4%, sleep disturbances of varying degrees and severity were observed in 11.7% of patients, more often in individuals over 30 years old.

In 73 patients (85.8%), exacerbations occurred in the autumn-winter period. In 12 patients (14.1%), seasonality of exacerbations was not observed. The frequency of exacerbations up to 4 times a year was in 68 patients, more than 4 times a year in 17 patients. The duration of exacerbation over 25 days was observed in 61 patients (71.7%).

Skin colonization of S. aureus and Candida fungi was revealed in all patients:

- more than 1000 CFU / dm ² - in 65.8% of patients;

- less than 1000 CFU / dm ² - 34.2% of patients (from 150 to 950 CFU / dm ² ).

Using simple randomization, patients were divided, depending on the treatment method, into 2 groups, comparable by sex, age, severity and duration of the disease, social conditions.

Group 1 (n-42) - received traditional therapy (control group);

Group 2 (n-43) - traditional therapy was combined with taking tilorone according to the scheme: 1st day - 0.250 g, 2nd day - 0.125 g and then three days later 0.125 g once a day after meals for 5 weeks . Reception of tilorone was repeated, regardless of clinical manifestations, after three months. The total dose for the entire course is 2.5 g.

Traditional systemic pharmacotherapy included the appointment of drugs that stabilize mast cell membranes (ketotifen, or zaditen), second-generation antihistamines (kestin, zirtec, erius), individually selected.

Particular attention was paid to the external therapy of A.D .: compresses with sorbent, perftoran and mineral water in a ratio of 1: 1: 2-3, then the external use of anti-inflammatory and emollient creams and ointments according to indications individually selected.

The effectiveness of the therapy was evaluated in the course of treatment, 6-12 and 24 months after completion of the course of treatment according to the following indicators:

- time of relief of clinical manifestations;

- the frequency and duration of relapse;

- normalization or tendency to normalize the initial changes in immunity indicators.

Against the background of the therapy, the effect of treatment in the form of reducing or stopping itching, stopping rashes was observed after 2-3 days in patients of group 2. On the 7-8th day of treatment, the intestinal function was restored in patients of this group, the concomitant symptoms decreased or disappeared.

The positive dynamics of clinical manifestations in patients of the 2nd group occurred 3-4 days earlier than in patients of the 1st group.

Indicators of immune status did not have statistically significant differences between the observation groups immediately after treatment. 3 months after the course of therapy, only the patients of the 2nd group maintained improved immunograms (tables 1, 2 and 4), in 25 patients (58.1%) of this group an elongation of remission was observed for more than 9 months (table 3), and the resulting exacerbations took less time (the average duration of treatment decreased from 25.4 days to 19.9 days).

When analyzing the immune status in patients A.D. before the start of therapy, there was a decrease in the number of lymphocytes in 21.2 ± 2.9%, a decrease in CD3, CD4, CD8 cells, respectively, in 24.8 ± 2.1% - 41.3 ± 3.4% and 25.8 ± 1 , 9% of patients, an increase in NK cells in 25.3 ± 1.7%, high phagocytic index in 11.2 ± 1.7% of patients, a decrease in spontaneous and induced LHLC (luminol-dependent chemiluminescence) by 43.4 ± 3.2 % and 22.4 ± 2.1%, respectively (table 5).

During treatment, the “Good” effect on clinical manifestations was observed in patients of the 1st group in 67.3 ± 3.4% of cases, in the 2nd group - in 84.3 ± 2.1% of patients. A "satisfactory" effect, respectively, in 31.3 ± 3.4% and 15.1 ± 0.2% of patients; there was no effect in 1.4 ± 0.4% of patients of the 1st group and in 0.6 ± 0 , 02% of patients of the 2nd observation group.

After a year, the frequency of skin colonization in patients with A. D. more than 1000 CFU / dm ² decreased by 3.9 times in patients taking tilorone according to the proposed scheme, and only 1.3 times in patients on the background of only traditional therapy (table 6) .

As can be seen from the data presented, there is a positive further dynamics of changes in the parameters of cellular immunity and the functional activity of neutrophils against the background of ongoing therapeutic and recreational activities in patients with A.D. in all observation groups. The most pronounced positive changes were revealed in patients of the 2nd group in terms of the functional activity of neutrophils.

Example 1. Patient K.N.E., 24 years old, has been suffering from atopic dermatitis since childhood. The disease lasted up to 12 years with frequent exacerbations, was widespread. After childbirth, from 18 to 22 years old, relative remission was observed. After stress, from 22 years old, an aggravation occurred again, and the inflammatory process took a continuously relapsing course, was accompanied by persistent skin itching, was widespread (on the SCORAD scale - 42-44%).

An allergy examination revealed sensitization to household allergens. In the blood test - HB - 118 g / l, l - 6.7 g / l, e-6, p-4, s-56, m-11, l-23, ESR - 21. In the smear, the skin imprint is highlighted staphylococci and fungi of the genus Candida, colonization of more than 1000 CFU / cm ² . Traditional therapy did not give the desired result; 2-3 months after the treatment, the disease again exacerbated. Over the year - 5-6 exacerbations, the average duration of exacerbation is 21.5 ± 2.3 days.

The patient for traditional therapy (hypoallergic diet, elimination of causative allergens, antihistamines and sedatives, skin care) was prescribed tilorone according to the scheme: on the first day - 0.250 g once a day, on the second day - 0.125 g / day and then after three days, 0.125 g for 5 weeks; after three months, the patient took 0.125 g of tilorone every 3 days another 10 times.

2 weeks after the start of therapy with tilorone, the patient's condition improved, skin rashes, and itching decreased. After 3 months in the blood test: HB - 128 g / l, l - 5.9 g / l, e-2, p-2, s-58, m-13, l-25, ESR - 11, colonization - less 100 CFU / cm ² . In the next 12 months there was only 1 episode of exacerbation, the duration of exacerbation was 14.5 days.

Example 2. Patient M.O.N., 23 years old, suffers A.D. since childhood. The prevalence on the SCORAD scale is 45-48%. Received traditional therapy. During pregnancy and during breastfeeding, there was a significant clinical improvement and the patient stopped following a hypoallergenic diet and elimination measures. 2 years after the birth of the child, the patient again had rashes on the skin of the body, in the popliteal fossae, in the elbow bends. The patient began to be bothered by stubborn skin itching. In blood tests, eosinophilia was noted - 10%, accelerated ESR - 21 mm.

Biochemical tests without features. Blood sugar - 4.7 mmol / L.

Total IgE - 420 IU / ml, specific IgE - positive with a group of household, bacterial and fungal allergens. Colonization of the skin with bacteria Staphyloccocus aureus and fungi of the genus Candida more than 1000 CFU / dm ² . Over the past year, there were seven exacerbations of A.D., which required the administration of systemic glucocorticosteroids and the prolonged use of combined hormonal ointments.

The patient was assigned tilorone according to the scheme described in Example 1, and locally compresses with peccecom and perftoran and mineral water in a ratio of 1: 1: 3 - only 5 compresses.

After a month of treatment, skin colonization decreased to 600 CFU / dm ² , and after three months to 25 CFU / dm ² . During the year of observation, the patient had only one episode of exacerbation of A.D. 11 days in duration (before treatment, the exacerbation duration was 22-25 days).

Example 3. Patient A. A. G., 29 years old, with a verified diagnosis of A. D., the prevalence on the SCORAD scale of 58-59%. The duration of the disease is 16.5 years, the frequency of exacerbations with purulent-destructive skin lesions is 5-6 times per year, mainly in the autumn-winter period, the duration of exacerbation was 18-22 days.

The effectiveness of traditional therapy (antibiotics, systemic corticosteroids, antihistamines, local therapy with combined corticosteroids) was low. The patient continued to be bothered by stubborn skin itching, the adherence of pustular elements of the rash during the period of exacerbation. In blood tests, eosinophilia was noted - 9%, accelerated ESR - 26 mm, blood sugar - 4.9 mmol / L.

Biochemical liver tests without features. Ultrasound of the abdominal cavity - no pathology revealed. Total IgE - 370 IU / ml, specific IgE - positive with a group of household, food, bacterial and fungal allergens. Colonization of the skin Staphyloccocus. aureus and fungi of the genus Candida more than 1000 CFU / dm ² .

The patient was assigned tilorone according to the scheme described in Example 1 for a course of 2.5 g and topical compresses with peccecom, perfluorane and mineral water in a ratio of 1: 1: 2 for a course of 5 compresses. After a month of treatment, skin colonization decreased to 450 CFU / dm ² , and after three months to 35 CFU / dm ² , total IgE decreased to 105 IU / ml.

Over the next year of observation of exacerbations A.D. did not have.

Thus, the given clinical examples and results of observations of 85 patients with a verified diagnosis of A.D. show that the appointment of tilorone in the complex therapy of severe and common forms of A.D., as well as the course of tilorone and the local use of compresses with sorbent, perfluorane and mineral water, are accompanied by a clearly expressed positive dynamics of both clinical and immunological parameters, and an improvement in microbiocenosis of the skin, quality of life for patients, i.e. provides increased efficiency in the treatment of severe and common forms of A.D. in adult patients.

Table 1 Change in indicators of humoral immunity factors. Indicators 1 gr before treatment 1 gr after treatment 1 gr after 3 months 2 gr before treatment 2 gr after treatment 2 gr after 3 months IgA g / l 1.8 ± 0.3 1.7 ± 0.2 1.6 ± 0.4 1.8 ± 0.4 2.1 ± 0.3 2.0 ± 0.2 IgM g / l 1.3 ± 0.2 1.2 ± 0.3 1.2 ± 0.1 1.2 ± 0.3 1.5 ± 0.2 1.4 ± 0.2 IgG g / l 14.6 ± 1.1 13.5 ± 0.9 11.9 ± 1.2 13.8 ± 0.9 15.1 ± 0.9 15.0 ± 1.1 IgE IU / ml 167.8 ± 11.3 162.7 ± 9.5 164.1 ± 13.1 164.9 ± 12.1 111.9 ± 11.1 104.5 ± 10.2 p <0.01

table 2 The dynamics of changes in the number of leukocytes, lymphocytes and their subpopulations Indicators 1 gr before treatment 1 gr after treatment 1 gr after 3 months 2 gr before treatment 2 gr after treatment 2 gr after 3 months White blood cells,% 5.5 ± 1.1 5.6 ± 0.9 5.4 ± 1.0 5.4 ± 1.1 5.8 ± 1.2 5.7 ± 1.0 Lymphocytes,% 24.0 ± 0.9 23.3 ± 0.6 22.8 ± 1.2 24.8 ± 1.1 24.9 ± 1.2 25.7 ± 1.1 CD3 +,% 54.9 ± 1.9 53.9 ± 1.8 53.2 ± 1.2 55.9 ± 1.9 64.3 ± 1.5 65.1 ± 1.4 CD4 +,% 36.5 ± 1.5 34.4 ± 1.8 34.0 ± 1.1 36.9 ± 1.2 37.1 ± 1.2 37.0 ± 1.3 CD8 +,% 26.1 ± 1.7 27.9 ± 1.5 26.2 ± 1.3 27.4 ± 1.9 31.0 ± 1.6 31.1 ± 1.2 3F3% 8.1 ± 0.5 9.3 ± 0.7 8.8 ± 0.4 7.8 ± 0.8 9.2 ± 0.5 9.3 ± 0.4 p <0.05

Table 3 Duration of remission The duration of remission 1 group before treatment 1 group after treatment 2 group
before
treatment 2 group after
treatment Up to 3 months 31.2 ± 3.0 36.1 ± 2.6 30.9 ± 2.9 67.4 ± 2.4 More than 9 months 27.4 ± 2.2 29.9 ± 2.7 26.9 ± 1.9 58.1 ± 2.3 p <0.01

Table 4 Changes in cytokines. Cytokines Research result 1 group before treatment 1 group after treatment after 12 months 2 group before treatment Group 2 after treatment after 12 months IL-4 Below normal 12 (28.5%) 11 (26.1%) 11 (25.5%) 8 (18.6%) Norm 14 (33.3%) 17 (40.4%) 14 (32.5%) 26 (60.4%) Above norm 16 (38%) 14 (33.3%) 18 (41.8%) 9 (20.9%) IL-8 Below normal 8 (19.0%) 7 (16.6%) 9 (20.9%) 8 (18.6%) Norm 13 (30.9%) 16 (38.0%) 12 (27.9%) 20 (46.5%) Above norm 21 (50.0%) 19 (45.2%) 22 (51.1%) 15 (34.8%) INF-y Below normal 29 (69.0%) 21 (50.0%) 30 (69.7%) 14 (32.5%) Norm 11 (26.1%) 19 (45.2%) 10 (23.2%) 28 (65.1%) Above norm 2 (4.7%) 2 (4.7%) 3 (6.9%) 1 (2.3%) p <0.05

Table 5 Dynamics of indicators of cellular immunity and changes in the functional activity of neutrophils by spontaneous and induced LHCL after 24 months Indicators CD3 decline CD4 decline CD8 decline SHL decline IHL reduction before after before after before after before after Before after 1st gr. 21,2 19.7 24.5 19.6 24.9 34.6 37,2 31.7 17.7 15.4 2nd gr. 20.1 16,2 24.7 17.1 26.9 38.8 29.9 19.2 17.6 11,2 p <0.05

Table 6 Dynamics of skin microbiocenosis Microbiocenosis rate 1 group before treatment Group 1 one year after treatment 2 group before treatment Group 2 one year after treatment more than 1000 CFU / dm ² 63.8 ± 3.0 46.1 ± 2.6 68.1 ± 2.9 17.4 ± 2.4 less than 1000 CFU / dm ² 36.2 ± 2.2 53.9 ± 2.7 31.9 ± 1.9 82.6 ± 2.3 p <0.05

Claims (3)

1. A method of treating atopic dermatitis, including the introduction of tilorone, characterized in that the tilorone is administered according to the scheme: 1st day - 0.250 g, 2nd day - 0.125 g and then after three days 0.125 g for 5 weeks; after three months, 0.125 g of tilorone is administered every three days another 10 times, regardless of clinical manifestations. 2. A method of treating atopic dermatitis, including the introduction of tilorone, characterized in that the tilorone is administered according to the scheme: 1st day - 0.250 g, 2nd day - 0.125 g and then after three days 0.125 g for 5 weeks; after three months, tilorone is administered 0.125 g every three days another 10 times, regardless of clinical manifestations, at the same time topically applied compresses with sorbent, perfluorane and mineral water in a ratio of 1: 1: 2-3. 3. The method according to claim 2, characterized in that enterosgel or peccecam is used as the sorbent.