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DERMATOVENEREOLOGY
INVENTION
Patent of the Russian Federation RU2266109

METHOD FOR TREATMENT OF LUMINOUS FORMS OF SKIN ANGIITES

METHOD FOR TREATMENT OF LUMINOUS FORMS OF SKIN ANGIITES

The name of the inventor: Ivanov O.L. (RU); Shekhter AB (RU); Kosheleva I.V. (RU); Zaborova VA
The name of the patent holder: State Educational Institution of Higher Professional Education. Moscow Medical Academy. THEM. Sechenova
Address for correspondence: 119992, Moscow, ul. Trubetskoy, 8, p. 2, MMA named after. THEM. Sechenova, Department of Intellectual Property
The date of the beginning of the patent: 2004.02.25

The invention relates to medicine, namely, to dermatology, and can be used for the treatment of peptic ulcer forms of skin angiitis. A method for the treatment of ulcerative forms of skin angiitis is proposed, which includes treatment of the spots of the eruption of the plasma-chemical nitrogen oxide by the gas flow, moving the flow along a concentric path from the perifocal zone to the center of the ulcer, from a distance of 25 cm to the phase of the exudative process 5 times a week and from a distance of 15 cm into the active phase Proliferation 3 times a week at an exposure time of 10 s per cm 2 on the background of taking tsiprolet, detraleksa, fenkarol and Aevita. This method allows you to shorten treatment time, reduce side effects by reducing inflammation, improving microcirculation, skin barrier function, regeneration processes.

DESCRIPTION OF THE INVENTION

The invention relates to medicine, namely dermatology, and can be used to treat ulcerative skin angiitis.

Angiitis of the skin (AK) is an actual problem of dermatology, which is caused by the growth of vascular diseases, stubborn, progressive progress and insufficiently developed methods of fighting them. AK occupy a significant place (up to 30%) in the structure of skin diseases. AK - a group of dermatoses, in which the initial and leading link in clinical and pathomorphological symptoms is nonspecific inflammation of the walls of dermal and hypodermal blood vessels of different calibres. At present, angiitis is considered as a pathology of polyethological, but monopathogenetic. In recent years the theory of immunocomplex genesis of angiitis, which connects their origin with the damaging effect on the vascular wall of immune complexes, is spreading more and more. Clinical manifestations of AK are diverse, but most often among polymorphous eruptions ulcerative skin defects (mainly on the lower extremities) are observed.

Modern approaches to the treatment of AK suggest the elimination or correction of various links in the pathogenesis of the disease. Ulcerative skin angiitis forms are the most severe and resistant to treatment, requiring the appointment of "therapia magna" - corticosteroids and cytostatics. And there is a large arsenal of topical agents (lotions, ointments, sponges), as well as modern physiotherapy methods: laser irradiation, oxygen-ozone therapy.

There is a method of treating AK with systemic corticosteroids. Treatment with prednisone begins with adequate doses (ie, doses that suppress the clinical and laboratory activity of the process for 1.5-2 weeks). The adequacy of the dose depends on the degree of activity and the stage of the process, as well as on the body weight of the patient. In the progressing stage with high activity and average body weight, an adequate dose will be 8-12 tablets of corticosteroid (40-60 mg / day). Women prone to fullness, it is preferable to prescribe drugs triamtsinolona (polkortolon, kenacort, triamcinolone), not giving a large increase in body weight. Urbazone is well tolerated. Perhaps the simultaneous use of two corticosteroids and in correspondingly reduced doses. An adequate dose of corticosteroid should be given to the patient for at least 3 weeks, after which a gradual decrease in the daily dose can be started. Treatment in total is stretched for several months and is considered in connection with this permanent. The approximate rate of decrease in the daily dose of corticosteroids looks like this: from 12 to 8 tablets, the daily dose is reduced by 1 tablet daily, from 8 to 6 - 1 tablet in 3 days, from 6 to 4 - by 1/2 tablet in 3 days, 4 tablets It is advisable to take about 1 month, and then reduce from 4 to 3 tablets per 1/2 tablets per week, from 3 to 2 tablets - by 1/2 tablet in 2 weeks, from 2 to 1 tablet - by 1/2 tablet in 3 Week, from 1 tablet to cancellation - 1/2 tablet a month (Nasonov E., Baranov AA, Shilkina NP Vasculitis and vasculopathy - Yaroslavl, Upper Volga, 1999).

Known in the art is the use of a cytostatic cyclophosphamide, an oral dose of 1-2 mg / kg / day or a pulse therapy of 500-1000 mg / m 2 / day (10-15 mg / kg / day) for the first 4-6 Months monthly, and then every 3 months (Luqmani R.A, Pall A., Adu D. et al., Therapy of vasculitis, In: The Vasculitides / Eds., Ansell, VM, Bacon PA, Lie J.T. , Yaadd H. - London, 1996. - P.315-331).

For the treatment of chronic AA, quinoline preparations are often used: chloroquine diphosphate (delagil) and hydroxychloroquine sulfate (plaquenyl). In addition to anti-inflammatory properties, these drugs suppress aggregation and adhesion of platelets and reduce the viscosity of the blood. The following doses are suggested in the course of treatment: a daily dose of plakvenyl 400 mg (6.5 mg / kg); Delagila 250 mg (4 mg / kg) (Petri M. Hydroxychloroquine use in the Baltimore lupus cohort: effects on lipids, glucose and thrombosis, Lupus, 1996.-Vol.5 (suppl.1) 22).

In complex therapy, the use of drugs that improve the delivery of oxygen to tissues is justified. One such remedy is pentoxifylline and its metabolites. The following scheme is suggested: treatment is started with intravenous drip infusions of pentoxifylline 200-300 mg / day in 200 ml of physiological solution. The course of treatment consists of 10-15 infusions. Immediately after the end of the infusion therapy, they switch to oral administration of the drug 600-800 mg / day for 30-40 days, followed by a decrease in the dose to 200-300 mg / day and its administration for a long time (6-12 months) (Matsubara T ., Yabuta K., Furukawa S. Treatment of Kawasaki disease with pentoxifylline, an inhibitor of TNF-alfa transcription // Cln. Research .-- 1994. Vol.42., P.751-756).

It is known that modern powerful anti-inflammatory drugs, primarily corticosteroids, cause arterial hypertension, hypercortisy, diabetes mellitus. Cytotoxic agents have undesirable side effects, especially with prolonged use: severe oppression of bone marrow hematopoiesis and impaired gastrointestinal function. Admission for a long time of aminoquinoline drugs requires constant monitoring of the level of leukocytes in the blood, liver function, and carrying out ophthalmological studies. Spasmolytic pentoxifylline (trental) with parenteral administration can cause arterial hypotension. The complex use of pharmacological drugs in patients with AK is often limited by the presence of concomitant diseases in these patients, and by the side effects of each of the medicines.

The method closest to the proposed method of treatment of peptic ulcer forms of skin angiitis is the method of prescribing PUVA therapy (UV irradiation with wavelength A of the spectrum) with a methoxalene photosensitizer at a dose of 4 J / cm 2 3 times a week with simultaneous administration of prednisolone in a dose 20 mg / day, pentoxifylline 1600 mg / day, aspirin 750 mg / day; Then the dose is increased by 1 J / cm 2 for each session. PUVA therapy was performed for 7 weeks, the total dose was 197 J / cm 2 (Choi H.-j., Hann S.- K. Livedo reticularis and livedoid vasculitis responding to PUVA-therapy // J. Amer., Acad. Of Dermatology - 1999 - vol.40 - №2 - p.456-463).

The disadvantage of this method of treatment is that the PUVA therapy because of its side effects is largely limited to the presence of the patient's violations of the liver and kidneys. In addition, an obvious disadvantage is that for the success of treatment, it is necessary to combine PUVA therapy with prednisolone and other medications, which aggravates the possibility of side effects.

The object of the present invention is to develop a method for treating ulcerative forms of AK, which can affect the etiopathogenesis of the disease, reduce side effects by eliminating cytotoxic agents and corticosteroids from the treatment complex, and shortening the duration of treatment.

The task is solved by the method consisting in combining medical treatment and treatment of the lesions of the gas flow of plasma-chemical nitrogen oxide from a distance of 15-25 cm from the outlet channel, moving the flow along a concentric path from the perifocal zone to the center of the ulcer with an exposure of 10 seconds per cm 2 Up to 5 times a week, only 7-10 sessions. With the procedures combine antibiotics (ciprolet), vascular drugs (detraleks), antihistamines (phencarol), vitamins (Aevit).

In practice, the method is carried out as follows. Apparatus "Plazon" was used in the stimulation mode - NO-therapy. The gas flow in this mode is formed by the manipulator at the maximum air flow rate. During the procedure, the remote controller is connected to the manipulator, providing a thermally safe distance. On average, the number of procedures was 10 sessions. During the period of predominance of the exudative component, the procedures were performed every day (5 times a week), but as the phase of active proliferation passes through the day (3-4 times a week). Exposure time was 10 seconds per square centimeter of the affected skin. The distance from the exit channel of the manipulator to the site of the lesion varied from 15 to 25 centimeters. As the distance decreases, the temperature of the gas stream increases, so it is important to ask the patient about subjective sensations.

As a source of nitric oxide, an air-plasma device "Plazon" of domestic production is used. The production of nitric oxide in the apparatus takes place in accordance with the plasma-chemical reaction N 2 + O 2 = 2NO. Atmospheric air is fed into the device with an integrated microcompressor, passes through an electric arc, heats up and accelerates, passing into the plasma state, then enters a two-stage cooler whose gas channels are made in a labyrinth circuit and forcedly cooled. This design allows the NO-containing gas stream to be produced at the output of the manipulator with a sufficiently low temperature and a high content of nitrogen oxide molecules.

Clinical examples:

Example 1 . Patient J. 46 years old, Muscovite, power engineer, was in the clinic of skin diseases MMA named. IM Sechenov 28 days with the diagnosis: polymorphic dermal angiitis, necrotizing-ulcerative type. Upon admission, he complained of multiple ulcers of the left shin, accompanied by severe pain. Concomitant diseases: ischemic heart disease, postinfarction cardiosclerosis, type 1 diabetes mellitus. Postponed diseases: myocardial infarction, coronary artery bypass grafting in 2002. It should be noted that single rashes on the shins began to appear more than 10 years ago, and the appearance of multiple unilateral rashes was preceded by an operative intervention - taking the donor shin vessel for CABG. Local status: the lesion focuses on the left shin and foot. The eruptions are polymorphous, represented by small edematous inflammatory spots-reddish-cyanotic ecchymosis and purple palpable purpura, and multiple ulcers, varying in size from 0.5 to 3 cm in diameter, rounded and irregular contours, single blisters (up to 1 cm in diameter) with serous And hemorrhagic contents. The left tibia is edematic, mainly in the ankle joint region, pulsation at the rear of the foot is reduced.

Conducted treatment: tsiprolet 500 mg 1 tab. 2 r / day, detraleks 1 tab. 2 r / day, fenkarol 1 tab. 3 r / day, Aevit 1 capsule 2 r / day, tavegil 0.001 1 tab. 2 r / day, NO-therapy. According to the scheme developed by us: 10 sessions were conducted. At the initial stage, the procedures were performed every day (5 times a week) with the distance from the output channel of the manipulator to the lesion site of 25 cm, and at the final stage - every other day (3 times a week) with a distance of 15 cm. The exposure time was 10 seconds for Cm 2 of affected skin. Since the first sessions, there has been a decrease in perifocal inflammatory phenomena, puffiness, active cleansing of ulcerative defects, and soreness has decreased. After the third procedure, bright pink granulations appeared, the size of the ulcers began to decrease, the pain disappeared. To the final sessions, the former sites of ulcerative defects were represented by a well vascularized granulation tissue. The treatment was tolerated by the patient well, without side effects.

Example 2 . Patient I. 84 years old, Muscovite, retired, was treated in the clinic of skin diseases MMA. IM Sechenov 21 days with a diagnosis: polymorphic dermal angiitis, necrotizing-ulcerous type. Upon admission, she complained of multiple ulcers of the legs, accompanied by soreness. Concomitant diseases: hypertension, cataract. Local status: the lesion focuses on the right and left shin, mainly in the lower half. Basically, the rashes are represented by ulcers having different sizes from 0.3 to 2.5 cm in diameter, rounded and irregular shapes, there are excoriations and perifocal peeling.

Conducted treatment: tsiprolet 500 mg 1 tab. 2 r / day, detraleks 1 tab. 2 r / day, fenkarol 1 tab. 3 r / day, Aevit 1 capsule 2 p / day, NO-therapy. According to the scheme, 7 sessions were conducted: the procedures were performed every other day with the distance from the output channel of the manipulator to the lesion site of 20 cm, the exposure time was 10 seconds per cm 2 of affected skin. There was a decrease in edema, active cleansing of the surface of ulcerative defects and the appearance of granulations, a decrease in soreness. The treatment was tolerated by the patient without side effects.

The proposed method was used to treat 19 patients, while in all cases a convincing positive effect (clinical cure or significant improvement) in the form of healing ulcerative defects, reducing edema and inflammatory phenomena, and disappearance of itching and soreness. In the treatment of side effects was not revealed, the procedures were well tolerated, and the patients themselves reported the rapid disappearance of pain, the appearance of "lightness" in the legs. The observation period of the patients is 6 months, there were no recurrences of the disease.

High clinical effectiveness of the proposed method of treatment is provided by combining the treatment of foci of gas-affected plasma-chemical nitric oxide with selected medications.

The method of the invention makes it possible to reduce the amount of prescribed drugs and shorten the duration of treatment.

CLAIM

A method for treating ulcerative skin angiitis, characterized in that the rash spots are treated with a gas stream of plasma-chemical nitrogen oxide, moving the flow along a concentric path from the perifocal zone to the center of the ulcer, from a distance of 25 cm into the phase of the exudative process 5 times a week and from a distance of 15 cm in Phase of active proliferation 3 times a week at an exposure time of 10 s / cm 2 on the background of taking tsiprolet, detralex, fenkarol and aevite.

print version
Date of publication 01.04.2007гг