RU2175244C2 - Method of treating chronic inflammatory dermatoses in children - Google Patents

Abstract

FIELD: pediatrics. SUBSTANCE: polyenzyme preparation Wobenzym in the form of dragee in intestine-soluble envelope following a regimen elaborated taking into account child age. EFFECT: achieved high therapeutic efficiency, prolonged remission time, and excluded adverse effects. 7 ex

Description

 The invention relates to medicine and relates to the pharmacotherapy of chronic inflammatory dermatoses in children.

 Alopecia areata, vitiligo, acne, focal scleroderma, psoriasis, eczema, late skin porphyria are very common dermatoses in children, occurring chronically with periodic exacerbations and often causing severe psychoemotional reactions due to a pronounced cosmetic deficiency, up to a violation of socio-psychological adaptation. The treatment of these patients presents serious difficulties due to insufficient knowledge of the pathogenesis of these diseases.

 Despite significant differences in the local clinical picture (foci of baldness, depigmentation and lichenization, pustular rashes, inflammatory atrophy spots, flaky papular, vesicular and bullous elements, etc.) arising as a result of impaired hair growth, pigmentation, keratinization, lightness etc., these patients have a number of common pathogenetic disorders. This is primarily the presence of inflammatory changes in the skin, accompanied by a more or less pronounced violation of microcirculation, the state of cellular and humoral immunity, vegetative and psychological status, as well as pathology from the gastrointestinal tract, nephrosystem and some other organs.

To achieve a positive effect in the treatment of these chronic inflammatory dermatoses, a large number of different means and methods are currently prescribed that affect one or another of the identified mechanisms of the disease:
a) general action - multivitamin complexes, angioprotectors, vasodilator drugs, sedatives, trace elements, immunocorrector, biogenic stimulants, photosensitizers, small tranquilizers;
b) local action - glucocorticoid, irritating and tonic ointments and creams, photosensitizing, keratoplastic, keratolytic, vasoconstrictive, astringent, drying and disinfecting and anti-inflammatory solutions, powders and pastes, etc .;
c) physiotherapeutic methods - ultraviolet radiation and D'Arsonval currents, vacuum massage, collar zone massage, phonophoresis of lesions, cryomassage, Bucca therapy, etc.

 Achieving a positive result in patients with chronic inflammatory dermatoses is complicated by the fact that in addition to various skin structures, most patients suffer from many organs and systems, i.e. these dermatoses are systemic diseases in which, depending on the severity of general disorders, the intensity of local inflammatory manifestations changes - from focal forms to universal damage to the entire skin.

 In recent years, on the one hand, there has been an increase in the number of patients with chronic inflammatory dermatoses with a severe course of the process and resistance to therapy, and on the other, an increase in side effects from the use of complex treatment complexes.

 However, even with such an integrated approach to treatment, the treatment periods for these diseases are often very long and even when using modern complex therapeutic complexes, they range from 6 months to 2-3 years. Moreover, children often have side effects and even complications caused by the ingestion of a large number of drugs that are diverse in terms of the mechanism of action.

 A known method of complex treatment of alopecia areata. This method of treatment is described in the "Guide to Pediatric Dermatovenereology" by Yu.K. Skripkin et al. , M .: Medicine, 1983 p. 344-347. In the specified source it is reported that in the treatment of alopecia areata a rational combination of pathogenetic agents is used, which are selected depending on the results of the examination of all organs and systems of the patient. For general exposure use: hormonal drugs (glucocorticoids, ACTH, thyroidin, growth hormone, anabolic drugs); vitamins (most often PP, folic acid, B5, B2, A and E); in the presence of neurotic conditions - small tranquilizers and sedatives (tazepam, seduxen, bromides, etc.); photosensitizers of the furocoumarin series of general and local action (psoberan, psoralen, beroxan, ammifurin, puvalen) in combination with ultraviolet radiation, trace elements (iron, copper, cobalt, arsenic, zinc). For local exposure use: a large number of irritating and tonic agents (Rosenthal paste, psoriasin, alcoholic and ethereal solutions containing sulfur, resorcinol, capsicum, as well as onion, garlic and aloe juice). Of the physiotherapeutic methods, the most commonly used are irrigation of foci with ethyl chloride, cryomassage with liquid nitrogen or snow of carbonic acid, border Bucca therapy, UFO, D'Arsonval currents, vacuum massage, collar zone massage, phonophoresis of foci of baldness with Aevit and hydrocortisone.

 The disadvantage of this method is its lack of effectiveness, in particular a large number of simultaneously used drugs, the presence of adverse reactions.

 An advantage of the claimed invention is to increase the effectiveness of treatment, increase the duration of clinical remission, the elimination of adverse reactions.

 The problem is solved in that a method of treating chronic inflammatory dermatoses in children consists in carrying out enzyme therapy using a polyenzyme preparation in the form of an enteric-coated tablet containing enzymes of animal origin in one tablet (pancreatin - 100 mg, chymotrypsin - 1 mg, trypsin - 24 mg) , amylase-10 mg, lipase - 10 mg), enzymes of plant origin (bromelain - 45 mg, papain - 60 mg), rutin - 50 mg, in a dose of 3 to 9 tablets per day, depending on age, while sick children at the age of 3 years to 7 p during the first 3 weeks, the drug is prescribed in 3 tablets per day; during the 4th week - 4 tablets per day; from the 5th week onwards for 1.5 - 2 months - 5 tablets a day, then if there is a positive dynamics in the clinical picture of the disease, the dose of the drug is reduced by 1 tablet per week in the opposite order; for sick children aged 7 years to 11, the drug is prescribed 3 tablets a day for the first 3 weeks; from the 4th to 7th week, the dose of the drug is increased weekly by 1 dragee; from the 7th week and then for 1.5-2 months - 7 tablets a day, then if there is a positive dynamics in the clinical picture of the disease, the dose of the drug is reduced by 1 tablet per week in the opposite order; for sick children aged 11 years to 14 years 11 months during the first 3 weeks, the drug is prescribed in 3 tablets per day: from the 4th to 9th week, the dose of the drug is increased weekly by 1 tablet; from the 9th week, for 1.5-2 months, the drug is given 9 tablets a day, then if there is positive dynamics in the clinical picture of the disease, the dose of the drug is reduced by 1 tablet per week in the opposite order.

 The prerequisites for the creation of the proposed method for the treatment of chronic dermatoses were the data obtained by the staff of the German pharmaceutical company MUKOS M. Wolf and K. Ranzberger about the presence of the anti-inflammatory, anti-edematous, improving microcirculation and rheological properties of the blood, which increases monocyte phagocytosis, that they developed for systemic enzyme therapy Wobenzym macrophages and the elimination of immune complexes of the action that destroys the immune complexes in the walls of small vessels and by improving microcirculation lyatsii promoting excretion products of the inflammatory process degradation. Wobenzym is a polyenzyme preparation that, in the form of an enteric-coated tablet, contains in one tablet: enzymes of animal origin (pancreatin - 100 mg, chymotrypsin - 1 mg, trypsin - 24 mg, amylase - 10 mg, lipase - 10 mg), plant enzymes origin (bromelain - 45 mg, papain - 60 mg), rutin - 50 mg. All of these positive properties of this drug made it possible to use it in the treatment of various diseases of inflammatory genesis, occurring with varying degrees of intensity and accompanied by impaired microcirculation. Due to its ability to reduce the severity of inflammation, Wobenzym dramatically accelerates the reparative processes in the body. This made it possible to widely recommend it in the treatment of any acute, subacute and chronic inflammatory processes. (Systemic enzyme therapy. Research and clinical practice. K.Nowz, Z. Masinowski, R. Mukhov. - Munich-Prague, 1994). Clinical trials have proven that systemic enzyme therapy reaches the level of effectiveness of standard treatments. Moreover, with enzyme therapy, patients are not at risk of unwanted side effects. Therefore, the course of treatment can continue as long as you like (Enzymotherapy. Review of clinical trials. G. Stauder, V. Pollinger, S. Frut, R. Mukhova, Munich-Prague, 1994).

 However, in chronic inflammatory dermatoses, the pathogenetic mechanisms of which are very promising for the effects of this drug, it has not yet been used, which served as the basis for the development of the proposed treatment method.

 Based on the above data, Wobenzym was used for the first time in the treatment of chronic inflammatory dermatoses (alopecia areata, vitiligo, acne, focal scleroderma, psoriasis, eczema, late skin porphyria) as a drug that affects microcirculation, stimulates repair and has an immunomodulatory effect. The novelty of the proposed method of treatment, in addition, lies in the use of a special children's "wave-like" intake regimen, depending on the age of the patients.

 The method is as follows.

Wobenzym is administered orally 30-40 minutes before meals, without chewing, drinking plenty of water (250 ml), depending on the age of patients in the following doses according to the following schemes:
a) From the age of 3 to 7:
- during the first 3 weeks, 3 tablets per day (1 in the morning, 1 in the afternoon and 1 in the evening);
- during the 4th week, 4 tablets per day (2 - in the morning, 1 - in the afternoon and 1 - in the evening);
- from the 5th week onwards for 1.5-2 months, 5 tablets a day (2 in the morning, 2 in the afternoon, 1 in the evening). After this period, in the presence of positive changes in the clinical picture and the data of a special examination, the dose is reduced by 1 tablet per week in the reverse order.

b) At the age of 7 years to 11:
- during the first 3 weeks, 3 tablets per day (1 - in the morning, 1-day and 1 - in the evening);
- during the 4th week, 4 tablets per day (2 - in the morning, 1 - in the afternoon and 1 - in the evening);
- during the 5th week, 5 dragees per day (2 in the morning, 2 in the afternoon and 1 in the evening);
- during the 6th week, 6 tablets per day (3 - in the morning, 2 - in the afternoon and 1 - in the evening);
- from the 7th week onwards for 1.5-2 months - 7 dragees per day (3 in the morning, 2 in the afternoon and 2 in the evening). After this period, in the presence of positive changes in the clinical picture and the data of a special examination, the dose is reduced by 1 tablet per week in the reverse order.

c) At the age of 11 years to 14 years, 11 months:
- during the first 3 weeks, 3 tablets per day (1 - in the morning, 1 - in the afternoon and 1 - in the evening);
- during the 4th week, 4 tablets per day (2 - in the morning, 1 - in the afternoon and 1 - in the evening);
- during the 5th week, 5 dragees per day (2 in the morning, 2 in the afternoon and 1 in the evening);
- during the 6th week, 6 tablets per day (3 in the morning, 2 in the afternoon and 1 in the evening);
- during the 7th week, 7 dragees per day (3 in the morning, 2 in the afternoon and 2 in the evening);
- during the 8th week, 8 tablets per day (3 in the morning, 3 in the afternoon and 2 in the evening):
- from the 9th week onwards for 1.5-2 months - 9 tablets per day (3 in the morning, 3 in the afternoon and 3 in the evening). After this period, in the presence of positive changes in the clinical picture and the data of a special examination, the dose is reduced by 1 tablet per week in the reverse order.

 At minimum maintenance doses, patients were treated until the skin manifestations of these diseases were completely resolved.

 The proposed method of treatment with Wobenzym was tested by the authors of the proposal in 246 patients (85 - alopecia areata, 50 - focal scleroderma, 25 - psoriasis, 45 - various eczema, 3 - late cutaneous porphyria, 20 - various forms of acne, 18 - vitiligo).

 To assess the effectiveness of the proposed method of treatment, we studied and analyzed in dynamics (before, during and after treatment): the state of the inflammatory process and other local clinical manifestations in the lesions (erythema, lichenization, weeping, hair growth intensity, pigmentation, etc.) the nature of the course of the disease and its relapses, the state of the neuro-psychological status and other clinical indicators of the treated diseases.

 As objective indicators of the positive effect of the drug in the dynamics (before and after treatment), the indicators of cellular and humoral immunity were evaluated: blood T and B lymphocytes, serum immunoglobulins (Ig), circulating immunocomplexes (CEC), chemiluminescent granulation (CG).

In the process of comparative observations, it was found that in the experimental group the effectiveness of treatment was significantly higher than in the control, namely:
- the time to achieve clinical recovery was reduced on average by 2 times (14-15 days instead of 28-30 days in hospital),
- the terms of clinical remission increased on average 2-8 times (from 1.5-6 months to 1-2 years).

 It should be emphasized that in the experimental group the majority of the commonly used the above drugs were not used, which on the one hand significantly reduced the consumption of scarce drugs, and on the other hand, reduced the drug load on the children's body and eliminated the occurrence of side effects from therapy. That is, the use of the Wobenzym preparation gave a pronounced clinical effect without additional use of the commonly used general drug therapy. In addition to the Wobenzym preparation, separate local symptomatic agents were prescribed for sick children.

 Example 1

 Extract from the medical history of the patient K.D. 13 years. Diagnosis: subtotal alopecia of the scalp, complicated by onychodystrophy. Sick from 11 years of age. During the year she repeatedly received complex treatment in various institutions with specialists of various profiles (dermatologist, neuropathol, endocrinologist) without effect. It has been observed since December 1995. On admission: hair on the head was completely absent; there was a thimble dystrophy of the nail plate of the hands. A laboratory study revealed a sharp decrease in serum levels of IgG, XT with a significant increase in CEC.

 The proposed method of treatment with Wobenzym was carried out from December 1996 to December 1997 in combination with conventional external therapy. Clinical observation showed that after a week from the start of treatment, the growth of individual hair appeared, and after 16 weeks - the hairline on the head was completely restored. In addition, six months after the start of treatment and 2 months after discontinuation of the Wobenzym preparation, the nails acquired a normal structure.

 Laboratory studies in dynamics (see table. 1).

 Studies have shown that during treatment with Wobenzym, the level of serum IgA, IgG, CG and CEC reached normal levels.

 Thus, the result of treatment was a complete recovery. The hairline and normal immune status lasts for 2.5 years.

 Example 2

 Extract from the patient’s medical history G.A. 3.5 years. Diagnosis: focal scleroderma of the plaque form in the stage of sclerosis. Sick from 3 years of age. It has been observed since November 1995. On admission: on the skin of the right temporal region, the right side of the chin, the right part of the forehead and the back along the spine there were several foci of sclerosis, round and linear in size from 3 to 5 cm, dense to the touch, ivory and with an inflammatory cyanotic nimbus. A laboratory study revealed a sharp decrease in serum IgA levels, a significant increase in CG and CEC; IgG were below the lower limit of normal.

 Initially, within 1 year, the child received the traditional complex treatment with an insignificant and temporary effect. Then he was transferred to the proposed method of treatment with Wobenzym, which was carried out from December 1996 to March 1997 in combination with local effects of conventional external therapy. Clinical observation showed that 10 weeks after the start of treatment, the lesions in the back disappeared without a trace. In foci on the face after 13-16 weeks, the sclerotic seal completely resolved. Only mild atrophy remains.

 Laboratory studies in dynamics (see table. 2).

 Studies have shown that during treatment with Wobenzym, serum IgA, IgG, CEC and CG levels returned to normal.

 Thus, the result of treatment was a complete clinical cure. Remission persists for 1.5 years.

 Example 3

 Extract from the patient’s medical history M.A. 14 years. Diagnosis: late cutaneous porphyria. Sick from 4 years of age. It has been observed since February 1995. On admission: on the skin of the face, forearms, legs and rear of the hands, against the background of erythema, there were scattered itchy vesiculate elements up to 1 cm in diameter with serous-hemorrhagic and purulent contents, leaving behind crusts, atrophic scars and hyperpigmentation. A laboratory study revealed a sharp increase in urine levels of uroporphyrins, coproporphyrins in feces and protoporphyrins. In addition, a secondary immunodeficiency state was detected with predominant damage to cellular immunity.

 Initially, within 1 year, the child received the traditional complex treatment with broad-spectrum antibiotics, vitamins, lipotropic drugs and anti-inflammatory and epithelizing external therapy with an insignificant and temporary effect. Then he was transferred to the proposed method of treatment with Wobenzym, which was carried out from December 1996 to December 1997 in combination with essentialia-fort and epithelizing external therapy. Clinical observation showed that after 6 months from the start of treatment, the lesion foci disappeared. In the period of the usual seasonal (spring-summer) exacerbation of relapses was not observed. Only tender scars remained in the lesions.

 Laboratory studies in dynamics (see tab. 3).

 Studies have shown that during the treatment of Wobenzym, the levels of CEC and CG returned to normal.

 Thus, the result of treatment was a complete clinical cure. Remission persists for 2 years.

 Example 4

 Extract from the medical history of the patient G.L. 12 years. Diagnosis: children's microbial eczema. Sick from 4 years of age. It has been observed since May 1995. On admission: on the skin of the face, upper and lower extremities against the background of erythema there were edematous areas with papules, vesicles, pustules, erosions and excoriations located on them. Marked itching was noted. A laboratory study revealed a sharp increase in the number of white blood cells and ESR. In addition, a secondary immunodeficiency state was found with the defeat of both humoral and cellular immunity.

 Initially, for 1 year, the child received the traditional complex treatment using desensitizing, antihistamines, broad-spectrum antibiotics, vitamins, external anti-inflammatory and epithelizing agents, and physiotherapy. The positive effect was insignificant and short-term. Then the patient was transferred to the proposed method of treatment with Wobenzym, which was given from January 1996 to May 1997 in combination with epithelizing and antipruritic external therapy. Clinical observation showed that after 6 months from the start of treatment, the lesions completely disappeared and have not yet appeared.

 Laboratory studies in dynamics (see tab. 4).

 Studies have shown that during treatment with Wobenzym, serum IgM, IgE, IgD, as well as CEC and CG levels returned to normal. Thus, the result of treatment was a complete clinical cure. Remission persists for 2 years.

 Example 5

 Extract from the medical history of the patient D.I. 14 years. Diagnosis: acne vulgaris, oily seborrhea. Sick from 11 years of age. It has been observed since September 1997. On admission: on the skin of the face, upper chest and back against the background of erythema there were numerous comedones, pustular elements, infiltrates, atheromas and scars. The hair on the head is greasy, sticky. Facial skin - oily, shiny. A laboratory study revealed iron deficiency anemia and a secondary immunodeficiency state with inhibition of IgG synthesis.

 Initially, for 1 year, the patient received traditional complex treatment using a diet that excludes easily digestible carbohydrates, fats, and includes lactic acid and protein products, vegetables and fruits. From drugs, she received broad-spectrum antibiotics, vitamins, anti-staphylococcal gamma globulin, sulfur and externally alcohol disinfectants. The positive effect was short-lived. Upon admission to the clinic after the examination, the patient was prescribed the proposed method of treatment with Wobenzym, which has been given since September 1997 for 4 months in combination with an external disinfectant therapy. This period was enough to completely eliminate the inflammatory elements on the skin. Currently in clinical remission.

 Laboratory studies in dynamics (see table. 5).

 Studies have shown that during treatment with Wobenzym, serum IgG, IgM, IgE, as well as CEC and CG levels have reached normal levels. The hemoglobin level in the blood also returned to normal.

 Thus, the result of treatment was a clinical cure. Remission lasts for 8 months.

 Example 6

 Extract from the medical history of the patient L.Yu. 8 years. Diagnosis: ordinary vitiligo. Sick from 5 years of age. It has been observed since April 1996. On admission: on the skin of the face around the eyes, mouth, chin, front of the neck, in the perineum, elbow and knee joints, under the shoulder blades there were depigmented milky-white spots of various shapes and sizes with clear edges. In a laboratory study, no significant changes were detected.

 Before going to the clinic, she was treated with selective photochemotherapy with complications in the form of a burn, which caused an exacerbation of the process on the skin. Upon admission to the clinic after the examination, at first for 2 months the patient received the traditional complex treatment, including vitamins, copper sulfate and externally containing silicon products. There was no positive effect. Then the patient was assigned the proposed method of treatment with Wobenzym, which has been given since March 1997 for 6 months in combination with external therapy. After 2 months, lesions of marginal repigmentation appeared in the lesion foci, after 6 months, the lesions on the face and knees completely repigmented, and the rest decreased in size. Repigmentation continues.

 Thus, as a result of treatment, a significant clinical improvement was noted.

 Example 7

 Extract from the patient’s medical history 10 years. Diagnosis: psoriasis of the palms and soles, exudative form. Sick from 6 years of age. It has been observed since September 1996. On admission: on the skin of the palms of the hands and especially the soles, a diffuse lesion was noted in the form of significant skin infiltration, hyperkeratotic layers, saturated with exudate. In addition, there were numerous deep fissures and deformation of the nail plates characteristic of psoriasis with the phenomena of subungual hyperkeratosis, as well as severe inguinal lymphadenitis and intense itching.

 In a laboratory study, in addition to lymphocytosis and hypoproteinemia, no significant changes were detected.

 Prior to admission to the clinic, he was treated according to traditional regimens using glucocorticoid drugs inside and out. This treatment gave a temporary insignificant effect and did not prevent seasonal relapses. Initially, for 2 weeks, the patient received the traditional complex treatment using desensitizing, antihistamines, vitamin preparations, essentiale-forte and external glucocorticoid and exfoliating therapy. Due to the lack of effect after the examination, the patient was transferred to the proposed method of treatment with Wobenzym, which has been given since October 1996 for 4 months in combination with Essential Forte and external exfoliating and epithelizing therapy. This period was enough to completely eliminate skin rashes. Currently, the skin is free from rashes, there are small changes in the nail plates in the form of onychodystrophy. Once a year receives seasonal preventive treatment with Wobenzym.

 Laboratory studies have revealed a positive trend in the above modified indicators.

 Thus, as a result of treatment, a stable clinical remission was obtained, which lasts for 2 years.

Claims (1)

 A method of treating chronic, inflammatory dermatoses in children by administering the drug Wobenzym, characterized in that for children aged 3 to 7 years, the drug is administered in the first three weeks of 3 tablets per day, for the 4th week - 4 tablets per day from the 5th week onwards for 1.5 - 2 months - 5 tablets a day, then, in the presence of positive dynamics in the clinical picture of the disease, the dose of the drug is reduced by 1 tablet per week in the opposite order; for children aged 7 to 11 years, the drug is administered during the first three weeks at 3 tablets per day, from the 4th to 7th week the dose of the drug is increased weekly at 1 tablet, from 7 weeks and then for 1.5 - 2 months - 7 tablets a day, then, in the presence of positive dynamics in the clinical picture of the disease, the dose of the drug is reduced by 1 tablet per week in the reverse order; for children from 11 years old to 14 years old 11 months during the first three weeks, the drug is administered 3 tablets a day, from the 4th to 9th week the dose of the drug is increased weekly by 1 tablet, from the 9th week and then for 1, 5 - 2 months - 9 tablets per day, then, in the presence of positive dynamics in the clinical picture of the disease, the dose of the drug is reduced by 1 tablet per week in the reverse order.

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