RU2264815C2 - Method for treating localized scleroderma - Google Patents

Abstract

FIELD: medicine, dermatology.

SUBSTANCE: the present innovation deals with treating different forms of localized sclerodermia: plaque, linear, scleroatrophic lichen, idiopathic atrophodermia. The method deals with introducing delagyl, xanthinol nicotinate, claritine, application of "Elocom" ointment. At the background mentioned one should alternate 8-10 procedures of intravenous injection of ozonized physiological solution at ozone concentration being 1.5 mg/l at the volume of 200 ml and 5-7 procedures of subcutaneous puncturing in lesion foci with oxygen-ozone gaseous mixture at ozone concentration of 2 mg/l. This mixture should be introduced along focal periphery at the volume of 10-30 ml. Intravenous injections should be carried out twice or thrice weekly, and subcutaneous puncturing - once or twice weekly. The innovation enables to decrease sickness rate due to increased velocity and full-value absorption of the ointment used, immunomodulating, antiphlogistic, collagen-formation and microcirculation normalizing effect of complex therapy, liquidation of tissue hypoxia and reflexogenic stimulation of body vascular system.

EFFECT: higher efficiency of therapy.

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Description

The invention relates to medicine, namely to dermatology, and can be used to treat various forms of limited scleroderma: plaque, linear scleroderma, sclerotrophic lichen, idiopathic atrophoderma Pasini-Pierini.

Limited scleroderma (OSD) is one of the urgent problems of modern medicine, primarily dermatology. OSD refers to chronic dermatoses of unclear etiology, occupying from 0.3 to 1% in the structure of dermatological pathology (the incidence of scleroderma is on average from 2 to 12 cases per million inhabitants, while in recent years there has been a steady tendency to increase the total number of patients). OSD is characterized by damage to the connective tissue of the skin with a predominance of fibro-sclerotic and vascular changes. The main complaints made by patients with OSD are skin changes, a feeling of tightness, tightness, numbness. Foci of lesion can be single and multiple, have different shapes - round, oval, linear, irregular - and color, depending on the stage of the disease, from bright pink to cyanotic, to white or brownish-brown. Depending on the stage of the pathological process in the foci of OSD, the phenomena of induction or atrophy of the skin can be expressed. All these phenomena, in addition to unpleasant subjective sensations, cause significant moral suffering for patients and significantly reduce their quality of life, as they are a serious cosmetic defect, especially if they are located in open areas of the body.

Traditional approaches to the treatment of OSD involve the elimination or correction of various links in the pathogenesis of the disease.

With rapidly progressing induction, antifibrotic agents are prescribed (D-penicillamine at a dose of 600-1000 mg / day, a herbal preparation madecassolum orally in the form of tablets of 30 mg / day and externally in the form of ointment and powder), prednisone 10-20 mg / day , ketotifen 1-2 mg / day, as well as enzymes (lidase). The appointment of various vasoactive drugs (vasodilators, calcium antagonists, antiplatelet agents and angioprotectors) is advisable at all stages of the disease ("Modern pathogenetic therapy of scleroderma" - L.A. Bolotnaya, I.M.Serbina / International Medical Journal, 1999, No. 3, p.56-58; "Treatment with systemic and focal scleroderma madecassol" - N.G. Guseva, M.N. Starovoitova, E.S. Mach / Ter. archive, 1998, No. 5, pp. 58-61).

However, even the most powerful anti-inflammatory drugs used in the treatment of OSD have undesirable side effects, especially with prolonged use (development of Itsenko-Cushing syndrome with systemic corticosteroid therapy, gastrointestinal upset, leukopenia, thrombocytopenia and agranulocytosis with antifibrotic agents, arterial hypotension with the appointment of vascular drugs).

Current trends towards a decrease in the volume of drug therapy contribute to the introduction of physiotherapeutic methods of treatment, combining several therapeutic effects. One of the newest non-drug methods of treating OSD is contact exposure to the skin of extremely high-frequency electromagnetic radiation of the millimeter range (EHF therapy) for 10 minutes daily, total exposure per session 40 minutes, for 15-20 days ("EHF therapy in the treatment of limited scleroderma "- A.V. Smirnov, G.Yu. Kurnikov, V.S. Perestoronina / Millimeter waves in biology and medicine, 2000, No. 2 (18), pp. 34-35).

However, EHF-therapy is undesirable for concomitant thyroid pathology, which is often observed in patients with OSD, as well as in the presence of pustular rashes on the skin.

Low-intensity laser irradiation of the OSD foci is also carried out in a gentle mode - locally, with a defocused beam of a helium-neon laser (red light with a wavelength of 0.63 μm) at an output power of 3-5 mW at the end of the fiber, and a spot diameter of 4 mm (power density 0.4 -0.6 mW / cm ² ) and exposure for each affected area for 3 minutes. Irradiation is carried out according to the field-by-field method, in one session no more than 3 skin fields daily, 8-10 procedures per treatment course against the background of traditional external treatment, including dimexide and Unna cream ("Clinical and immunological features and modification of complex treatment for focal scleroderma of the external genitalia in girls using course low-intensity laser therapy "- V.F. Kokolina, E.I. Kharybina, I.L. Ukolova, E.S. Kireeva / Pediatrics, 2001, No. 3, p.106-108) . In the presence of multiple rashes, it is necessary to carry out several courses of treatment for 2-3 weeks each.

When conducting laser therapy, however, it is necessary to take into account a number of pathologies that are often found in patients with scleroderma and are contraindications to this method of treatment: diseases of the cardiovascular system, diabetes mellitus, thyroid disease.

There is a method of treating OSD with various stages of the skin process (early inflammation and later - sclerosis and atrophy) by applying low doses of ultraviolet radiation with a wavelength of "A" spectrum - a single dose of 20 J / cm ² 4 times a week for 6 weeks and then once a week for another 6 weeks (Effects of low dose ultraviolet A-1 phototherapy on morphea "(" Effect of low doses of ultraviolet radiation with A-wavelength on limited scleroderma ") Gruss, -CJ; Von- Kobyletzki, -G; Behrens-Williams, -SC et al. / Photodermatol-Photoimmunol-Photomed. 2001 Aug; 17 (4): 149-55).

It is also proposed to combine ultraviolet irradiation of the "A" spectrum (340-400 nm) with application of an ointment containing calcipotriol (0.005%) to the lesions twice a day. In this case, irradiation at a dose of 20 J / cm ^{2 is} carried out 4 times a week for 10 weeks - until a cumulative dose of 800 J / cm ² is reached ("Combined treatment with calcipotriol ointment and low-dose ultraviolet A1 phototherapy in childhood morphea" - "Combined treatment with an ointment containing calcipotriol and low doses of ultraviolet radiation with a wavelength of the A spectrum for limited scleroderma in children ") Kreuter, -A; Gambichler, -T; Avermaete, A. et al. / Pediatr-Dermatol. 2001 May-Jun; 18 (3): 241-5).

The disadvantage of treatment with the use of long-wave ultraviolet radiation is its long duration, as well as the fact that due to side effects it is largely limited to the presence of impaired parenchymal organs in the patient - the liver and kidneys. In addition, as can be seen from the above example, an obvious drawback is that for the success of treatment it is necessary to combine phototherapy with other medications, which exacerbates the possibility of side effects.

The method of interval hypoxic therapy is also used to treat OSD. The technique consists in intermittent (5-20 inclusions) inhalation of a hypooxygenated (10-15%) gas mixture with a partial oxygen pressure of up to 76 mm Hg. The main factors of action on the body of hypoxia is the inclusion of all the body's transport systems (increased pulmonary ventilation, increased minute blood circulation, increased regional blood flow, increased capillary tissue of the body), at the same time there is an increase in the activity of oxidative phosphorylation ("Experience in the use of interval hypoxic therapy in dermatological practice" - V.I. Kulagin, I.V. Khamaganova, A.G. Shekrot and others / Russian Journal of Skin and Venous Diseases. Moscow, 1998, No. 3, p. 29-31).

The application of this technique requires special equipment and special safety precautions. It should be borne in mind that inhaling a gas mixture with a low oxygen content may not be indifferent for patients with concomitant respiratory tract pathology. The course of treatment lasts 30 days; repeated courses from 10-15 sessions are carried out in 2-3 months (3-4 courses in total).

Closest to the proposed method for the treatment of OSD is a method consisting in the appointment of hyperbaric oxygenation (HBO) procedures carried out against a background of complex therapy, including penicillin, lidase, andecalin, angioprotectors, vitamins, topically lotions with 10-30% dimexide solution ("Hyperbaric oxygenation in the complex therapy of plaque scleroderma ". - S. S. Kryazheva, T. I. Sapronova, L. M. Bulokhova. / Russian Journal of Skin and Venous Diseases. Moscow, 1998, No. 4, p. 39-41 )

However, it should be borne in mind that the HBO method requires complex special equipment and extensive facilities, in addition, carrying out HBO procedures in a number of patients causes emotional discomfort (claustrophobia). In addition, HBO is recommended to be combined with active medication (penicillin, lidase, trental, aevit, compresses with a 30% solution of dimexide) and begin on the 5-7th day from its beginning. The total duration of treatment is 22-28 days.

The objective of this invention is to develop a simpler, not associated with the use of special equipment, method of treating limited scleroderma, which can reduce side effects by eliminating antifibrotic agents from the treatment complex and reducing the number of vascular preparations and their doses.

In practice, the task is carried out in the following way: Delagil is prescribed at 0.25 g per day, xantinol nicotinate at 0.15 g 2 times a day, claritin 0.001 g at night, externally on the lesions, Elok ointment 1 time per day, prescribed within 3 weeks and, against this background, 8-10 procedures of intravenous infusion of physiological saline enriched with the oxygen-ozone mixture and 5-7 procedures for subcutaneous injections of the oxygen-ozone mixture in the foci of scleroderma alternate (every other day).

To obtain the oxygen-ozone mixture, the automatic ozone therapeutic unit UOTA-60-01 "MedOzon" was used. Saturation of saline with medical ozone (ozonation) was carried out in standard bottles until the concentration of ozone in the solution was 1.5 mg / l; ozonized physiological saline (OGF) was administered to the patient intravenously using standard single-use systems in an amount of 200 ml, with an injection rate of 60-80 drops per minute. When carrying out subcutaneous chipping of lesions with an oxygen-ozone gas mixture, a 20 ml disposable plastic syringe was filled with an oxygen-ozone gas mixture with a concentration of ozone in a mixture of 2 mg / l, which was then injected subcutaneously to the patient at the periphery of the lesion focus in the amount of 10-30 ml ( depending on the size of the focus). Procedures were prescribed from the first day of taking medications (intravenous infusions alternated every other day with subcutaneous chipping). Intravenous infusions of FGs were performed 2-3 times a week, subcutaneous injections of the gas mixture 1-2 times a week.

Clinical examples

1) Patient K., 65 years old, retired. She complained of the presence of multiple rashes on the skin of the trunk and limbs, accompanied by a feeling of tightening the skin. Sick for 3 years, repeatedly received outpatient and inpatient treatment with various corticosteroid ointments, vitamins A and E, antihistamines, twice - courses of penicillin therapy. The treatment gave a short-term positive effect in the form of a regression of hyperemia and puffiness of the skin, however, after 6 months after the end of the last course of treatment, the progression of the skin process was noted in the form of fresh rashes on the skin of the thighs and the phenomena of skin atrophy in the foci on the skin of the chest and abdomen. Local status: on the skin of the abdomen, front, outer and inner thighs, foci of whitish-cyanotic color of round and irregular outlines, up to 5-7 cm in diameter; slight wrinkling of the skin in the lesions, resembling crumpled tissue paper, is noted.

Clinical diagnosis: Limited scleroderma, proceeding as a scleroatrophic lichen.

A course of drug therapy was prescribed: delagil 0.25 g 1 time per day, xanthinol nicotinate 0.15 g 2 times a day, clarithin 0.001 g 1 time per night, externally: Elok ointment 1 time per day. At the same time, a course of oxygen-ozone therapy was carried out in the form of intravenous infusions of OGF with an ozone concentration in solution of 1.5 mg / L No. 10 and subcutaneous chipping of the lesions along the periphery with an oxygen-ozone gas mixture with an ozone concentration of 2 mg / L No. 5. The treatment was tolerated without side effects. As a result of the course of treatment carried out over 21 days, a significant clinical improvement was noted in the form of the cessation of the appearance of fresh foci, changes in the color of the rashes to a “warmer” - shade close to the color of normal skin, smoothing of the skin, the disappearance of the feeling of skin tightening. Persistent clinical remission for 8 months.

2) Patient K., 58 years old, electrician. He complained of rashes on the skin of the chest and abdomen, skin tightening in the lesions. Sick for 11 years, repeatedly received outpatient and inpatient treatment: repeated courses of penicillin therapy, B vitamins, intramuscular injections of lidase, externally corticosteroid and emollient ointments and creams. As a result of the previous treatment, the progression of the process was suspended (fresh rashes did not appear at the time of treatment for 5 years), however, skin induction phenomena remained in the foci on the skin of the chest and abdomen. Local status: on the skin of the chest and anterior abdominal wall foci of skin lesions of a brownish-cyanotic color of irregular shapes up to 10 cm in diameter; the skin in some lesions on the abdomen is shiny, tightened; the remaining foci are hyperpigmented (brownish-brown), the skin in them is atrophic.

Clinical diagnosis: Plaque (inductive-atrophic) scleroderma.

The following treatment was carried out: delagil 0.25 g 1 time per day, xanthinol nicotinate 0.15 g 2 times a day, clarithin 0.001 g 1 time per night, externally: Elok ointment 1 time per day; intravenous infusions of OGF with an ozone concentration in solution of 1.5 mg / L No. 8 and subcutaneous chipping of lesions with an oxygen-ozone gas mixture with an ozone concentration in a mixture of 2 mg / L No. 7. The treatment was tolerated without side effects. As a result of the course of treatment carried out over 21 days, a significant clinical improvement was noted in the form of softening of skin induction in the lesion foci, repigmentation (restoration of normal color) of the skin. During the 7 months of follow-up, the treatment remained positive.

The proposed method treated 51 patients, while in 92% of cases a positive clinical effect was achieved (significant clinical improvement or complete regression of rashes) in the form of cessation of signs of progression of the skin process, softening of induction, restoration of normal color and smoothing of the skin, the disappearance of the feeling of tightness. No side effects were noted. It takes 3 weeks to complete the course of treatment with our proposed method, while it takes 1-2 1-2 months or more to achieve the clinical effect using only traditional medications.

The high clinical effectiveness of the proposed method of treatment is provided by a combination of oxygen-ozone therapy with selected drugs. The anti-inflammatory effect of the proposed treatment complex is caused by the activation of cellular metabolism and the work of the antioxidant system, which are realized with the systemic introduction of therapeutic doses of ozone into the body, as well as by external application of the Elok corticosteroid ointment to the lesion sites. At the same time, the possibility of developing side effects from steroid therapy is minimized due to the fact that, firstly, they are applied locally, and secondly, it is sufficient to apply the selected external drug only 1 time per day. The normalizing collagen formation and the moderately pronounced immunosuppressive effect of the aminoquinoline drug delagil is complemented by the immunomodulating effect of the systemic introduction of the ozone mixture into the body, which consists in the activation of phagocytosis, as well as the modulating effect on humoral immunity. In addition to the well-known biological properties of the ozone mixture, it is possible, when combined with its systemic and local administration, together with the drugs prescribed in the treatment complex, it has a pronounced effect on improving microcirculation at the level of the vessels of the dermis and hypodermis, improving oxygen supply to tissues, and eliminating the effects of tissue hypoxia.

Claims (1)

A method of treating limited scleroderma, characterized in that delagil, xanthinol nicotinate, clarithin are administered, the ointment "Elokom" is used and against this background, 8-10 procedures of intravenous administration of ozonized physiological solution with an ozone concentration of 1.5 mg / l in a volume of 200 ml are alternated and 5-7 procedures for subcutaneous chipping of lesions with an oxygen-ozone gas mixture with an ozone concentration of 2 mg / l, introducing this mixture at the periphery of the lesion in a volume of 10-30 ml, while intravenous administration is carried out 2-3 times a week, and subcutaneous chipping 1 - Two times per week.