RU2576834C2 - Method of treating eczema - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention concerns a method of treating eczema, characterised by the fact that a routine therapeutic approach is added by coating the involved skin area with 0.1% tacrolimus for 1 month in the morning and evening, and then for 2 months, once before bedtime; when using tacrolimus, applying any other agents on the skin area coated with tacrolimus and taking water procedures shall be avoided.

EFFECT: invention enables reducing or eliminating the risk of side effects and tachyphylaxis, and prolonging the remission.

2 ex

Description

The present invention relates to medicine, namely to dermatology and occupational pathology, and can be used to treat eczema.

Among allergic dermatoses, one of the most common is eczema, which occurs in 10-40% of all cases of skin lesions (Kubanova A.A. et al., 2006). Eczema is one of the three leaders among occupational diseases, it accounts for 90% of all occupational dermatoses (van Coevorden AM. PhD Thesis. Rijksuniversiteit, Groningen; 2005. Hand eczema. Clinical efficacy of interventions, and burden of disease). High economic costs are associated with disability, reduced quality of life for patients (Cvetkovski RS, Rothman KJ, Olsen J, Mathiesen B, Iversen L, Johansen JD, Agner T. Relation between diagnoses on severity, sick leave and loss of job among patients with occupational hand eczema. BrJ Dermatol. 2005; 152 (1): 93-98. doi: 10.1111 / j.1365-2133.2005.06415.x.) Thus, the problem of effective treatment of eczema is quite relevant. Currently, corticosteroid hormones are the drugs of choice for local treatment of this disease, but their long-term use is associated with a wide range of side effects (atrophy, telangiectasia, striae, acne, folliculitis, etc.), as well as the development of tachyphylaxis. The above creates the need for alternative safe methods of long-term local treatment.

Topical calcineurin inhibitors may be an alternative to corticosteroids. The main advantages of calcineurin inhibitors compared to corticosteroids are more pronounced selectivity of action, the absence of significant systemic absorption and many side effects of corticosteroid therapy. Topical calcineurin inhibitors (tacrolimus, pimecrolimus) inhibit not only the production of calcineurin and the expression of cytokine genes, but also inhibit the activation of skin T-lymphocytes and Langerhans cells involved in the pathogenesis of eczema. The effectiveness of calcineurin inhibitors has been demonstrated in a number of recent Russian and foreign studies in the treatment of psoriasis, seborrheic dermatitis, plaque scleroderma (Luger T, Paul C. Potential new indications on topical calcineurin inhibitors. Dermatology 2007; 215 (Suppl 1): 45-54. Epub 2007 Dec 18; NN Potekaev, VV Vavilov. Evaluation of the efficacy of topical Tacrolimus therapy for focal scleroderma in adults using the mLoSSI index. Clinical Dermatology and Venereology. 6, 2013. P. 46-51.)

Thus, it seems relevant decision aimed at pathogenetically sound use of topical calcineurin inhibitors in order to optimize the treatment of eczema.

A known method of treating eczema using corticosteroid agents for external therapy (Clinical recommendations. Dermatovenerology. 2010 / [edited by A.A. Kubanova]. - M .: DEKS-Press. - 428 S.). These drugs have anti-inflammatory, anti-allergic and antipruritic effects. Corticosteroid ointments (creams) are applied in a thin layer to the affected areas of the skin once / twice a day. Within 30 minutes after the use of corticosteroids, it is not recommended to apply any other drugs to the area covered with the corticosteroid, or to take water procedures. The course of treatment is determined individually for each patient, depending on the severity of the disease. The disadvantages of the method include the risk of numerous side effects of local corticosteroid therapy, often irreversible, as well as a decrease in the therapeutic effect with prolonged use, i.e. the development of tachyphylaxis.

For the closest analogue, a method of treating eczema with a topical corticosteroid mometasone furoat 0.1% in the form of an ointment with a thin layer of 1p./day was adopted. (Clinical recommendations. Dermatovenerology. 2010 / [edited by A. A. Kubanova]. - M.: DEKS-Press. - 428 p.) The duration of treatment is determined by the doctor for each patient individually. Within 30 minutes after the use of mometasone furoate, it is not recommended to apply any other drugs to the area covered by this agent, or to take water procedures. Numerous side effects are noted: burning, itching, skin rash, and paresthesia. With prolonged use of the drug, exacerbation of skin diseases, furunculosis, dry skin, contact allergic dermatitis, erythema, nausea, secondary infections, as well as the development of irreversible side effects such as skin atrophy, hypertrichosis, hypopigmentation, striae are possible.

With prolonged use, it is possible to develop systemic side effects, including inhibition of hormone production by the adrenal cortex. The development of tachyphylaxis (a decrease in the therapeutic effect with prolonged use) is characteristic. The listed side effects and the phenomenon of tachyphylaxis limit the time of use of mometasone furoate, while eczema often requires long courses of external therapy to completely resolve the rashes and achieve long-term remission.

Tasks:

- reducing the risk of side effects;

- elimination of the likelihood of developing tachyphylaxis;

- creating the possibility of prolonged use of the drug;

- increasing the effectiveness of therapy

The essence of the invention is that, against the background of the standard procedure, instead of local corticosteroid drugs, tacrolimus is applied to the affected areas of the skin with a 0.1% thin layer for 1 month in the morning and evening, and then for 2 months once, at night, and within 2 hours after using tacrolimus exclude the application to the area covered with tacrolimus, any other means, the reception of water procedures.

Technical result: the use of the method reduces the risk of side effects and eliminates the development of tachyphylaxis, the consequence of which is the possibility of a longer use of the drug tacrolimus, an increase in the therapeutic effect, which is justified by the fact that tacrolimus, being an inhibitor of calcineurin in chemical structure and pharmacological action, differs from corticosteroid hormones.

Tacrolimus binds to the cytosolic protein immunophilin (FKBP12), the resulting complex inhibits the activity of calcineurin, which leads to inhibition of T-cell transduction signaling pathways and prevents the transcription of genes encoding the production of cytokines that are key for the T-cell immune response.

In addition, tacrolimus inhibits the transcription of genes encoding the production of a number of cytokines (IL-3, IL-4, TNFα, etc.), which are involved in the activation of T-lymphocytes.

In addition, under the influence of tacrolimus, there is an inhibition of the release of inflammatory mediators from mast cells, basophils and eosinophils, a decrease in the expression of FcεRI (high affinity surface receptor for immunoglobulin E) on Langerhans cells, which leads to a decrease in their activity and presentation of antigen to T-lymphocytes.

The method is as follows: against the background of the standard methodology (Clinical recommendations. Dermatovenerology. 2010 / [under the editorship of A.A. Kubanova]. - M .: DEKS-Press. - 428 p.) Replace the use of local corticosteroid drugs by applying to the use of local corticosteroids by applying a tacrolimus ointment with a 0.1% thin layer for 1 month in the morning and evening, and then for 2 months once, at night, and 2 hours after using tacrolimus on the portion of the coated tacrolimus, any other means, receiving water treatments.

The method was tested on 53 patients, including: 23 men, 20 women aged 18-65 years for 2 years. The results are tabulated.

Table Indicators The treatment according to the proposed method Control group (standard method) Side effects + +++++ Duration of use of the drug 90 days It was determined individually, but not more than 90 days The cure% 95% 80% Lack of tachyphylaxis (addiction) + -

Example 1

Patient B. Diagnosis: dyshidrotic eczema. On admission: the skin pathological process is widespread, symmetrical, localized on the skin of the hands. Presented: erythema, microvesicles, peeling, peels, weeping. On the skin of the hands of the hands, on the lateral surfaces of the fingers, against a background of bright erythema, numerous microvesicles with a dense tire with a diameter of up to 0.3 cm, weeping areas, fine plate peeling, areas of exfoliating epidermis, layering of serous crusts are localized on the periphery of the foci. There is an alternation of areas of healthy and affected skin. Subjective: severe itching, burning.

Survey conducted:

OAK: red blood cells - 4.8 · 10 ⁹ / l, white blood cells - 8.4 · 10 ⁹ / l, hemoglobin - 150 g / l, color pok. - 0.9 sticks. - 3%, seg. - 57%, lymph. - 34%, monots. - 4%, eos. - 2%

B / X blood test - bilirub. Total - 14 μmol / l, creatinine - 82 μmol / l, glucose - 3.82 mmol / l, total protein - 63.8 g / l, cholesterol - 3.41 mmol / l , AST - 28 U / L, ALT - 30.5 U / L, albumin - 35.7 g / L, triglycerides - 0.89 mmol / L, GGT - 13 g / L, Amylase DiaS 55.5 g / L urea 3.2 mmol / l

OAM: col. - yellow, beats. weight - 1010, pH - 5.0 epithelium pl. - units in p / sp, white blood cells - units in p / sp.

Blood for syphilis: ELISA - negative, RMP - negative.

A blood test for hepatitis B, C: Hbs Ag - not obn., ATK HCV - not obn .; Blood test for HIV - AH / AT HIV not detected

Scraping of scales from m / finger folds of the feet: no mushrooms were found.

Prescribed treatment:

Medication: Phys. a solution of 0.9% - 200.0 + a solution of Thiosulfate Na 30% - 10.0 in / drip 1 time per day daily No. 10.

Inside: loratodine 10 mg 1 r./day 20 days; hydrolytic lignin 0.5-1 g / kg g 3 r. / day for 2 weeks, bromohydrochlorophenylbenzodiazepine 0.25-0.5 1-2 r. / day 7-9 days.

External therapy: 2% solution of boric acid 2p / day; methylene blue water 2% 2p. / day, ointment Tacrolimus 0.1% 2p. / day for 1 month. 1st re-visit (after 15 days): there is a positive dynamics of the skin pathological process. Complaints of moderate itching. There are no new rashes. Erythema is extinguished, weeping has decreased, on the lateral surfaces of the fingers of the hands single microvisicules, point erosion is visualized, peeling is not observed.

In / in the infusion, administration of bromohydrochlorophenylbenzodiazepine and hydrolysis lignin are completed. Continue external therapy according to the above scheme.

2nd re-visit (after 30 days): the skin pathological process regresses. No new items. There are no complaints. Erythema is extinct, no weeping is noted, erosion is epithelized, and there are single serous crusts along the periphery of the foci.

Repeated examination:

OAK: red blood cells - 4.8 · 10 ⁹ / l, white blood cells - 8.4 · 10 ⁹ / l, hemoglobin - 150 g / l, color pok. - 0.9 sticks. - 3%, seg. - 57%, lymph. - 34%, monots. - 4%, eos. - 2%

B / X blood test - bilirub. Total - 23 μmol / l, bilirub. Direct - 4.7 μmol / L, creatinine - 67 μmol / L, glucose - 4.58 mmol / L, total protein - 73.3 g / L, cholesterol - 3.67 mmol / L, AST - 28.7 E / l, ALT-32.4E / l, albumin - 40.7 g / l., GGT - 17 g / l, amylase - 50 g / l, urea 4.3 mmol / l.

OAM: color - yellow, beats. weight - 1005, pH - 6.0, epithelium pl. - 2-3 in n / a, white blood cells - 1-2 in n / a.

The intake of loratadine, the application of boric acid and methylene blue are completed. Appointed: ointment tacrolimus 0.1% once, daily, at night.

Final visit (after 90 days): dermatosis in remission, skin pathological process is not visualized. There are no complaints. Long-term results (examination after 6 months): dermatosis in remission. The patient is in the dispensary.

Example 2

Patient F. Diagnosis: true eczema.

On admission: the skin pathological process is widespread, symmetrical, localized on the skin of the hands. Presented: erythema, microvesicles, erosion, crust, weeping. On the skin of the hands of the hands against a background of bright erythema, numerous microvesicles with a diameter of up to 0.3 cm, pinpoint erosion, areas of weeping, layering of serous crusts. There is an alternation of areas of healthy and affected skin. Subjective: severe itching.

Survey conducted:

OAK-er - 4.3 · 10 ¹² / l, Hb - 136 g / l, color. - 0.9, leukoc. - 6.0 · 10 ⁹ / l, ESR - 7 mm / h, pal. - 2, seg - 55, lymph. - 37, mon - 2, eos - 3.

B / X blood test - bilirub. Total - 12 μmol / l, glucose - 5.06 mmol / l, creatinine - 82 μmol / l, total protein - 75.6 g / l, cholesterol - 4.09 mmol / l , ACT - 21.7 u / l, ALT - 21.5 u / l, GGT-19 U / l, albumin 40.7 g / l.

OAM - the color of St. yellow, specific weight - 1030; pH - 5.5, epithelium - units. in p / s;, white blood cells - units. in p / s.

Blood for syphilis: IFA - neg, RMP - neg.

Blood for HIV - AT / AT HIV was not detected.

Blood test for hepatitis: Hbs Ag - not obn., AT to HCV - not obn .; Scraping on mushrooms from the interdigital folds of the feet (from 02.17.14.) - no mushrooms were found in the scales.

Prescribed treatment:

Medication: Physical solution 0.9% - 200.0 + solution Calcium gluconate 10% -10.0 w / o cap No. 10, Physical solution 0.9% 200.0 + solution Sodium thiosulfate 30% -10.0 w / v drip 1 time per day daily No. 10.

Inside: loratodine 10 mg 1 r./day 20 days; hydrolytic lignin 0.5-1 g / kg g 3 r. / day for 2 weeks, bromohydrochlorophenylbenzodiazepine 0.25-0.5 1-2 r. / day 7-9 days.

External therapy: 2% solution of boric acid 2R./day; Methylene blue water 2% 2p. / Day, ointment Tacrolimus 0.1% 2p. / Day.

1st re-visit (after 15 days): there is a positive dynamics of the skin pathological process. Complaints of moderate itching. There are no new rashes. Erythema is fading, weeping has decreased, erosion is epithelized.

In / in the infusion, administration of bromohydrochlorophenylbenzodiazepine and hydrolysis lignin are completed. Continue external therapy according to the above scheme.

2nd re-visit (after 30 days): the skin pathological process regresses. No new items. Erythema is extinct, no weeping is noted, erosion is epithelized, and there are single serous crusts along the periphery of the foci.

Repeated examination:

OAK-er - 4.2 * 1012 / l, Hb - 130 g / l, col. - 0.9, leukoc. - 5.8 * 109 / l, ESR - 4 mm / h, pal. - 2, seg. - 54, lymph. - 37, mon - 2, eos - 3.

B / X blood test - bilirub. Total - 12 μmol / l, glucose - 4.08 mmol / l, creatinine - 81 μmol / l, total protein - 73.6 g / l, cholesterol - 4.02 mmol / l , ACT - 20.7 u / l, ALT - 21.5 u / l, GGT - 19 U / l, albumin 40.3 g / l.

OAM - the color of St. yellow, specific weight - 1030; pH - 5.5, epithelium - units. in p / s;, white blood cells - units. in p / s.

The intake of loratadine, the application of boric acid and methylene blue are completed. Appointed: ointment tacrolimus 0.1% once, daily, at night.

Final visit (after 90 days): dermatosis in remission, skin pathological process is not visualized. There are no complaints.

Long-term results (examination after 6 months): dermatosis in remission. The patient is in the dispensary.

Claims (1)

A method of treating eczema, characterized in that against the background of a standard treatment technique, including intravenous administration of calcium gluconate and / or sodium thiosulfate, the administration of loratadine, hydrolytic lignin and bromohydrochlorophenylbenzodiazepine, the use of boric acid and aqueous methylene blue as an external therapy, is additionally applied to the affected skin areas, tacrolimus preparation 0.1% for 1 month in the morning and in the evening, and then for 2 months once a night, and for 2 hours after using tacrolimus CA exclude the application to the area covered with tacrolimus, any other means and the reception of water procedures.