RU2266109C2 - Method for treating ulcerous forms of skin angiitis - Google Patents

Abstract

FIELD: medicine, dermatology.

SUBSTANCE: one should treat eruptive area with a gaseous flow of plasmochemical nitrogen oxide by replacing the flow along concentric trajectory against perifocal area towards ulcerous center, from the distance of 25 cm at the phase of exudative process 5 times weekly and from the distance of 15 cm during active proliferation thrice weekly at exposure time being 10 sec/sq.cm at the background of ciprolet, detralex, phencarol and aevit intake. The present innovation enables to decrease side effects due to deteriorating inflammatory processes, improving microcirculation, skin barrier function and regenerative processes.

EFFECT: higher efficiency of therapy.

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Description

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

Skin angiitis (AK) is an urgent dermatology problem, which is caused by the growth of vascular diseases, persistent, progressive course and insufficiently developed methods of dealing with them. AKs occupy a significant place (up to 30%) in the structure of skin diseases. AK is 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 various calibers. At present, angiitis is considered as a polyetiological pathology, but monopathogenetic. In recent years, the theory of the immunocomplex genesis of angiitis has been spreading more and more, linking their occurrence with a damaging effect on the vascular wall of immune complexes. The clinical manifestations of AK are diverse, but ulcerous defects of the skin (mainly on the lower extremities) are most often observed among polymorphic rashes.

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

There is a method of treating AK with systemic corticosteroids. Treatment with prednisone begins with adequate doses (i.e. 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 stage of the process, as well as on the patient’s body weight. In the progressive stage, with high activity and average body weight, an adequate dose would be 8-12 tablets of a corticosteroid (40-60 mg / day). For women prone to overweight, it is preferable to prescribe triamcinolone preparations (polcortolone, kenacort, triamcinolone), which do not give a large increase in body weight. Urbazone (metipred) is well tolerated. Perhaps the simultaneous use of two corticosteroids and in correspondingly reduced doses. The patient should receive an adequate dose of corticosteroid for at least 3 weeks, after which you can begin to gradually reduce the daily dose. The treatment lasts a total of several months and is considered permanent in this regard. The approximate rate of decrease in the daily dose of corticosteroids is as follows: from 12 to 8 tablets, the daily dose is reduced by 1 tablet daily, from 8 to 6 - by 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 tablet per week, from 3 to 2 tablets - 1/2 tablet in 2 weeks, from 2 to 1 tablet - 1/2 tablet in 3 weeks, from 1 tablet to withdrawal - 1/2 tablet per month (Nasonov E.L., Baranov A.A., Shilkina N.P. Vasculitis and vasculopathy. - Yaroslavl, Upper Volga, 1999).

A known method of treating AK with the use of cyclophosphamide cytostatic - oral administration at a dose of 1-2 mg / kg / day or pulse therapy 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 V.M., Bacon PA, Lie J.T. , Yaadd H. - London, 1996 .-- P.315-331).

Quinoline preparations are often used to treat chronic AK: chloroquine diphosphate (delagil) and hydroxychloroquine sulfate (plaquenil). In addition to anti-inflammatory properties, these drugs inhibit platelet aggregation and adhesion and reduce blood viscosity. The following doses are suggested during treatment: a daily dose of plaquenil 400 mg (6.5 mg / kg); delagil - 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). P.16- 22).

In the complex therapy of AK, the use of drugs that improve the delivery of oxygen to tissues is justified. One of these agents is pentoxifylline and its metabolites. The following scheme is proposed: treatment begins with intravenous drip infusions of pentoxifylline at 200-300 mg / day in 200 ml of physiological saline. The course of treatment consists of 10-15 infusions. Immediately after the end of infusion therapy, they switch to oral administration of the drug at 600-800 mg / day for 30-40 days, followed by a dose reduction 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, hypercorticism, and diabetes mellitus. Cytostatics have undesirable side effects, especially with prolonged use: severe inhibition of bone marrow hematopoiesis and impaired gastrointestinal function. Taking for a long time aminoquinoline drugs requires constant monitoring of the level of leukocytes in the blood, liver function, as well as conducting ophthalmological studies. Antispasmodic pentoxifylline (trental) with parenteral administration can cause arterial hypotension. The complex prescription of pharmacological drugs in patients with AK is often limited by the presence of concomitant diseases in these patients, as well as the side effects of each of the medicines.

Closest to the proposed method for the treatment of ulcerative forms of skin angiitis is a method consisting in the appointment of PUVA therapy procedures (UV irradiation with wavelength A of the spectrum) with a methoxalen photosensitizer at a dose of 4 J / cm ² 3 times a week while prescribing prednisone in a dose 20 mg / day, pentoxifylline at 1600 mg / day, aspirin at 750 mg / day; then the dose is increased by another 1 J / cm ² at each session. PUVA therapy was carried out 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 - No. 2 - p. 456-463).

The disadvantage of this treatment method is that PUVA therapy due to its side effects is largely limited to the presence of impaired liver and kidney function in a patient. In addition, an undoubted drawback 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 objective of the invention is to develop a method for the treatment of ulcerative forms of AK, which can influence the etiopathogenesis of the disease, reduce side effects by eliminating cytostatics and corticosteroids from the treatment complex, and reduce the treatment time.

The problem is solved by the method consisting in combining drug treatment and treatment of lesions with a gas stream of plasma chemical nitric oxide from a distance of 15-25 cm from the outlet channel, moving the stream 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. Antibiotics (ciprolet), vascular preparations (detralex), antihistamines (fencarol), vitamins (aevit) are combined with procedures.

In practice, the method is as follows. The apparatus "Plason" was used in the stimulation mode - NO-therapy. The gas flow in this mode is formed by the manipulator at maximum air flow. During the procedure, a spacer is attached to the manipulator, providing a thermally safe distance. The average number of procedures was 10 sessions. During the period of predominance of the exudative component, the procedures were carried out every day (5 times a week), and as the transition to the phase of active proliferation every other day (3-4 times a week). The exposure time was 10 seconds per square centimeter of affected skin. The distance from the output channel of the manipulator to the lesion site 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, the Plazon air-plasma apparatus of domestic production is used. Obtaining nitric oxide in the apparatus occurs in accordance with the plasma-chemical reaction N ₂ + O ₂ = 2NO. Atmospheric air is supplied to the device by a built-in microcompressor, passes through an electric arc, heats up and accelerates, turning into a plasma state, then enters a two-stage cooler, the gas channels of which are made in a labyrinth scheme and are forcedly cooled. This design allows you to get at the output of the manipulator NO-containing gas stream with a sufficiently low temperature and high content of nitric oxide molecules.

Clinical examples:

Example 1. Patient J., 46, a Muscovite, power engineer, was in the clinic of skin diseases MMA named after I.M.Sechenova 28 days with a diagnosis of polymorphic dermal angiitis, necrotic-ulcerative type. On admission, he complained of multiple ulcers of the left lower leg, accompanied by severe pain. Concomitant diseases: coronary heart disease, post-infarction cardiosclerosis, type 1 diabetes. Past diseases: myocardial infarction, coronary artery bypass grafting in 2002. It should be noted that single rashes on the legs began to appear more than 10 years ago, and the appearance of multiple unilateral rashes was preceded by surgery - taking a donor vessel for the leg for CABG. Local status: the lesion focuses on the left lower leg and foot. Rashes are polymorphic, represented by small edematous inflammatory spots - reddish-cyanotic ecchymoses and purple palpable purpura, as well as multiple ulcers, which vary in size from 0.5 to 3 cm in diameter, round and irregular outlines, single blisters (up to 1 cm in diameter) with serous and hemorrhagic contents. The left lower leg is swollen, mainly in the ankle joint, the pulsation on the back of the foot is reduced.

Treatment: ciprolet 500 mg 1 tab. 2 r / day, detralex 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 our scheme: 10 sessions were conducted. At the initial stage, the procedures were carried out every day (5 times a week) with a distance from the manipulator's output channel 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 per cm ² affected skin. From the first sessions, there was a decrease in perifocal inflammatory phenomena, swelling, active cleansing of the surface of ulcerative defects, and soreness decreased. After the third procedure, bright pink granulations appeared, the size of the ulcers began to decrease, the pain disappeared. By the final sessions, the former sites of ulcerative defects were represented by well-vascularized granulation tissue. The treatment was well tolerated by the patient, without side effects.

Example 2. Patient I. 84 years old, a Muscovite, a pensioner, was treated in the clinic of skin diseases MMA named after I.M.Sechenova 21 days with a diagnosis of polymorphic dermal angiitis, necrotic-ulcerative type. On admission, she complained of multiple leg ulcers, accompanied by soreness. Concomitant diseases: hypertension, cataract. Local status: the lesion focuses on the right and left lower leg, mainly in the lower half. In general, rashes are represented by ulcers, which have different sizes from 0.3 to 2.5 cm in diameter, rounded and irregular in shape, there are excoriations and perifocal peeling.

Treatment: ciprolet 500 mg 1 tab. 2 r / day, detralex 1 tab. 2 r / day, fenkarol 1 tab. 3 r / day, Aevit 1 capsule 2 r / day, NO-therapy. According to the scheme, 7 sessions were conducted: the procedures were carried out every other day with a distance from the manipulator's output channel to the lesion site of 20 cm, the exposure time was 10 seconds per cm ^{2 of} affected skin. A decrease in puffiness, active cleansing of the surface of ulcerative defects and the appearance of granulations, a decrease in soreness were noted. Treatment was tolerated by the patient without side effects.

The proposed method treated 19 patients, and in all cases a convincing positive effect was achieved (clinical cure or significant improvement) in the form of healing of ulcerative defects, reducing swelling and inflammation, as well as the disappearance of itching and soreness. When treating side effects were not detected, the procedures were well tolerated, and the patients themselves reported the imminent disappearance of pain, the appearance of "lightness" in the legs. The follow-up period for patients is 6 months, no relapse of the disease was noted.

The high clinical effectiveness of the proposed method of treatment is ensured by a combination of treatment of lesions with a gas stream of plasmochemical nitric oxide with selected drugs.

The method according to the invention allows to reduce the number of prescribed drugs and to shorten the treatment time.

Claims (1)

A method of treating ulcerative forms of skin angiitis, characterized in that the rashes are treated with a gas stream of plasma-chemical nitric oxide, moving the stream 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 in phase of active proliferation 3 times a week with an exposure time of 10 s per cm ² while taking ciprolet, detralex, fencarol and aevit.