RU2455982C1 - Method of treating patients with mycosis fungoides - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to dermatology and can be used for treatment of patients with mycosis funcoides. For this purpose therapy with PUVA-baths with solution of photosensitiser is performed 3 times a week. Additionally with PUVA-baths at the background of symptomatic therapy: antihistamine preparations, external ointment therapy administered are corticosteroid hormone prednisolone perorally in adaptive dose 0.3 mg/kg/day during 15-20 days and 10 intramuscular injections of immunomodulator - interal in dose 1 mln IU every second day. PUVA baths are carried out with total course of 10 sessions.

EFFECT: method makes it possible to achieve clinical improvement in patients with application of smaller cumulative course doses of UVA, which leads to reduction of risk of side effects and reduction of hospital treatment duration.

2 ex, 3 tbl

Description

The invention relates to medicine, namely to dermatology, and can be used to treat patients with fungoid mycosis.

Mushroom mycosis (GM) is the most common form of T-cell malignant lymphomas of the skin, the basis of which is neoplastic proliferation and accumulation of genetically modified clonal lymphocytes in the system of lymphoid tissue associated with the skin (N.A. Probatova, N.N. Tupitsin, E .V. Fleishman. Basic principles and diagnostic criteria for the revision of the European-American classification of lymphoid tumors (T-cell lymphomas, Hodgkin's disease) // Pathology Archive, - 1998, - No. 4, - P.61-70; Rodionov AN , Barbinov V.V., Kazakov D.V. Gist biological diagnostics of skin lymphomas // Journal of Dermatovenerology and Cosmetology. - 1997. - No. 1. - P.5-14; Yastrebov V.V., Raznatovsky I.M. Lymphomas of the skin. - 2000. - P.3-74).

The etiology and pathogenesis of GM are not well understood and remain debatable to this day. Among the variety of etiological factors leading to the development of GM, the theory of viral exposure is discussed, where the leading role in the development of T-cell lymphoproliferation is assigned to type I lymphotropic virus (HTLV-1), type C retrovirus, Epstein-Barr virus, types 7.8 herpes viruses and cytomegalovirus (Silver NB Connection of the Epstein-Barr virus infection with HLA - phenotype and features of the cytokine status in patients with malignant non-Hodgkin lymphomas // Issues of Virology. - 1998. - No. 2. - P.79-82; Khalidova H. R., Alimukhamedova Yu.A. And enzyme-linked immunosorbent assay of specific immunoglobulins of classes M and G for cytomegalovirus infection with skin lymphomas // Abstracts of the VIII All-Russian Congress of Dermatovenerologists. - M., 2001. - Part 1. - P.155-156; Shimakage M. et al. Expression of Epstein- Barr virus in cutaneous T-cell lymphoma including mycosis fungoides // Int. J. Cancer. - 2001. - Vol. 92 (2). - P.226-231; Girardi M. The Pathogenesis of Mycosis Fungoides // New England Journal of Medicine. - 2004 .-- Vol. 350 (19). - P.1978-1988).

The development of their genetic instability, which leads to the accumulation of genetic damage beyond a critical level (Vinogradskaya G.R. PCR - technologies in the diagnosis, prognosis and control of cancer therapy, is considered to be the central link in the mechanism of transformation of "normal" lymphocytes into neoplastically altered ones // Oncology Issues. - 2001. - T. 47. - No. 1. - C.7-16; Burg G. From inflammation to Neoplasia // Arch. Dermatol. - 2001. - Vol.137. - P.949-952). The alleged cause of pathological lymphoproliferation in the skin is chromosomal abnormalities: translocations of t (14; 18), t (10; 14) and aberrations of chromosome regions leading to the activation of proto-oncogenes. The further process of accumulation of genetically modified lymphocytes in the skin occurs due to their uncontrolled division under conditions of activation of oncogenes and incapacitation of the mechanisms of tumor suppression, apoptosis and cell cytotoxicity (Novik A.A. Molecular genetic approach to the diagnosis of malignant lymphomas // Oncology issues. - 1998. - T.44. - No. 3. - P.274-279; Thangavelu M. Recurring structural chromosome abnormalities in peripheral blood lymphocytes of patients with mycosis fungoides / Sezary syndrome // Blood. - 1997. - Vol. 89 (9). - P.3371-3377; Penninger JM Molecular and cellular mechanisms of T lymphocyte apoptosis // Adv. Immunol. - 1998. - Vol.68. - P.51-144).

Treatment of patients with GM is a very complex therapeutic problem, requiring a balanced approach both from the point of view of the clinical effectiveness of modern drugs and from the point of view of assessing the risk of possible complications and immunosuppression against the background of its implementation. The literature emphasizes that the use of aggressive treatment technologies does not improve the overall prognosis of the disease or the quality of life of patients. In this regard, the use of gentle therapeutic technologies is recommended, including the use of adjuvant immunotropic drugs that reduce the duration of high doses of corticosteroids and the patient’s hospital stay, and prevent further relapse of the disease.

The basic drugs for the treatment of GM are corticosteroid hormones (GCS) in doses of 0.5-1.0 mg / kg / day (in terms of prednisone), as well as cytostatics of various pharmacological groups: plant origin, synthetic, alkylating, antimetabolites and antitumor antibiotics . The listed drugs are not highly selective and do not allow to achieve complete remission of the disease, which leads to the need for the appointment of repeated courses of treatment (Clinical recommendations - dermatology / edited by A.A. Kubanova. - M.: GEOTAR-Media, 2006. - 320 p. )

Prednisolone - a synthetic analogue of the glucocorticosteroid hormone cortisone, has anti-inflammatory, anti-allergic, desensitizing, immunosuppressive and antitoxic effects. The immunosuppressive effect is realized in suppressing the migration of stem cells of bone marrow and B cells, disrupting the interaction of T and B lymphocytes, and inhibiting the development of lymphoid tissue (Mashkovsky MD Medicines, part II. - 1997. - P.28-30 ) In the treatment of GM, systemic and topical corticosteroids hormones (mainly prednisone) are used as monotherapy in doses of 30-60 mg / day, which, however, is more applicable in patients with early stages of development of GM and provides a satisfactory clinical effect of achieving remission only in 43.8 % of patients with stage 3 disease development (Rodionov A.N. Erythrodermic skin lymphoma (Study Guide), Leningrad, 1989, 67 pp .; Kalamkaryan A.A., Berenbein B.A., Potekaev N.S. Current problems of the clinic , diagnosis, pathogenesis, treatment of malignant lymphomas to women and Kaposi’s sarcomas // Bulletin of Dermatology and Venereology. - 1991. - No. 7. - P.18-26; Lezvinskaya EM Cytological diagnosis of malignant lymphomas of the skin, proceeding by the type of erythroderma: Dis .... Dr. med. M., 1997 .-- 239 p.). Thus, GCS monotherapy with hormones is effective in the early stages of the development of the process (GM stages 1 and 2) is relatively effective in patients with stage 3 disease.

Treatment with glucocorticosteroids at doses of 30-60 mg / day (in terms of prednisone) has significant negative changes in the cellular, humoral immunity and endocrine system, causing an increase in immunodeficiency. At the same time, treatment with supportive (15-30 mg / day) doses of corticosteroids has a moderate immunostimulating effect, induces the formation of receptors for growth factors on the cells, leads to a moderately inhibitory effect on endocrinological parameters (Korolkova TN et al. Effect of glucocorticoid therapy on immunological and endocrinological indicators in patients with low grade malignant skin lymphomas // Journal of Dermatovenereology and Cosmetology. - 1997. - No. 1. - P.25-30).

Among modern effective methods of treating patients with stage I-III GM, photochemotherapy (PUVA) occupies a special place - a combination of long-wave ultraviolet radiation and a photosensitizer. The PUVA therapy method is based on a combination of ultraviolet radiation (UV) in the spectrum of 320-390 nm and methoxalene (0.3-0.6 mg / kg of methoxalene is taken once 1 hour before irradiation). The rhythm of irradiation is 2-4 times a week. The main course of treatment is 25-30 procedures. The initial dose of ultraviolet radiation is 1.5-2 J / cm ² , every two procedures, the dose is gradually increased by 1.5-2 J to a maximum of 12-14 J / cm ² with a radiation density of 10-12 mW / cm ² . The exposure time is from 2 to 18 minutes.

In recent years, considerable experience has been accumulated about the side effects of this treatment method: the occurrence of dyspeptic disorders, photodermatitis, hypertrichosis, cheilitis, acne, candidiasis and other complications. In addition, in the long-term follow-up of patients who had a history of PUVA therapy, cases of the development of various malignant neoplasms of the skin were revealed: basal cell skin cancer, squamous cell carcinoma and melanoma (Querfeld C., Rosen ST, Kuzel TM et al. Long-term follow-up of patients with early-stage cutaneous T-cell lymphoma who chieved complete remission with psoralen plus UV-A monotherapy.Arch. Dermatol. - 2005. - Vol.141. - P.305-311).

The use of photosensitizers inside has a number of contraindications (severe liver and kidney dysfunction, cataract, aphakia) and adverse reactions (dyspeptic symptoms, dizziness, headache, palpitations, depression, hypotension, prolonged photosensitization of the eyes and skin, etc.), which significantly limit the use of PUVA therapy in clinical practice. In this regard, in recent years, the method of balneo-PUVA therapy (PUVA baths) has been used, when the photosensitizer is not administered orally, but externally when taking baths with a photosensitizing drug dissolved in water (Lindeloef B., Sigurgeirsson B., Tegner E . et al. Comparison of the carcinogenic potential of trioxsalen bath PUVA and oral methoxsalen PUVA. Arch. Dermatol. - 1992. - Vol.128. - P.1341-1344).

A special place in publications of recent years is occupied by reports on the use of methods of treatment of GM using natural and recombinant interferons, cytokines and retinoids, the rationale for the purpose of which is the identified defects of nonspecific and immunological reactivity in patients (Heald P. The treatment of cutaneous T-cell lymphoma with a novel retinoid. // Clin. Lymphoma - 2000. - Vol. 1 (1). - P. 45-49 .; Duvic M. Treatment of cutaneous T-cell lymphoma from a dermatologist's perspective // Clin. Lymphoma. - 2000 . - Vol. 1 (1). - P.15-20., 2000).

The prototype of the invention is a method for the treatment of patients with GM, used in dermatological practice to date, which consists in conducting PUVA baths with a solution of a photosensitizer (8-methoxypsoralen) 3 times a week for 63 days. This method was used to treat 16 patients with GM (11 men and 5 women) whose average age at the time of therapy was 53.2 ± 3.9 years (Weber F., Schmuth M., Sepp N. et al. Bath-water PUVA Therapy with 8-Methoxypsoralen in Mycosis Fungoides. Acta Derm Venereol - 2005. - Vol. 85. - P.329-332).

This method of treating patients with GM, presented as a prototype of the invention, is affordable and technically feasible in a dermatological hospital, however, achieving clinical improvement in patients is associated with the use of significant cumulative course doses of UVA, a significant increase in the risk of side effects and an increase in the duration of inpatient treatment.

The objective of the invention is to increase the effectiveness of the treatment of patients with fungoid mycosis.

The technical result of the invention is to increase the clinical effectiveness of the treatment of patients with GM while reducing cumulative radiation exposure, reducing the duration of inpatient treatment, minimizing the risk of side effects and complications from the therapy.

The technical result of the invention is achieved by the fact that for the treatment of patients with fungal mycosis by conducting PUVA baths with a photosensitizer solution 3 times a week, an additional corticosteroid hormone prednisolone is administered orally at an adaptive dose of 0.3 mg / kg / day for 15- 20 days and 10 intramuscular injections of an immunomodulator - integral of 1 million ME every other day, and PUVA baths are carried out in a general course of 10 sessions.

The essence of the invention lies in the combination of the administration of adaptive doses of the corticosteroid hormone prednisone, integral and PUVA baths with a photosensitizer - 0.3% solution of amifurin.

The immunobiological preparation Interal has antitumor, antiviral and immunomodulating activity.

Interal is a new domestic human recombinant interferon alpha-2, the main active principle of which is a protein synthesized by a pseudomonad strain, in the genetic apparatus of which the human leukocyte interferon alpha-2 gene is integrated. The preparation is a white powder or porous mass; it contains human donor albumin as a stabilizer. The established immunomodulatory, antiviral and antitumor properties of interal are recorded in the Register of Medicinal Products of the Russian Federation (2008 edition) and substantiate the possibility of its use as an adjuvant in the complex treatment of diseases, including viral and proliferative, accompanied by impaired immune status. Contraindications for the use of the drug are hypersensitivity, severe forms of allergic diseases and pregnancy. It is used by intramuscular injection. Immediately before use, the contents of the ampoule are dissolved in 1 ml of water for injection. The solution of the drug should be transparent, without impurities. The dissolution time before the injection should not exceed 4 minutes. Assign 1-3 million ME daily or every other day for 10-20 days, depending on nasology. After the clinical effect is achieved, supportive therapy is possible for 6-7 weeks.

Ammifurin photosensitizer (Solutio Ammifurini 0.3%, LSR-001964/07 of 08/07/2007) for external use is available in the form of a 0.3% alcohol solution and is a mixture of furocoumarins (isopimpinellin, bergapten and xanthotoxin).

The use of PUVA baths with a total course of 10 sessions and the simultaneous oral administration of prednisolone in an adaptive dose of 0.3 mg / kg / day, as well as intramuscular injections of interal at 1 million ME every other day are necessary and sufficient to ensure high clinical efficacy of treatment of patients with GM and prevention of the onset of side effects from ongoing therapy.

From an analysis of the scientific, technical and patent literature, the claimed combination of treatment methods for patients with fungoid mycosis, which leads to a significant reduction in cumulative radiation exposure, a reduction in the duration of inpatient treatment, and minimization of the risk of side effects and complications from the therapy, which ultimately ensures the clinical effectiveness of the therapy, we not identified, which allows us to conclude that the proposed solutions meet the criteria of "novelty" and "inventive step".

The invention is as follows.

A method of treating patients with fungoid mycosis is used in a specialized dermatological department with a full hospital regimen.

Patients with fungal mycosis against the background of symptomatic therapy (antihistamines and external ointment treatment) are prescribed the corticosteroid hormone prednisone and intramuscular administration of interal. At the same time, PUVA baths with a 0.3% solution of amifurin are carried out.

The main parameters of the PUVA bath technique: the final concentration of the photosensitizer - ammifurin in a solution of 1 mg / l, water temperature 36-37 ° C, the duration of the bath is 15 minutes. UVA irradiation is carried out immediately after taking a bath, after wiping the patient’s skin dry with a towel. The initial radiation dose is prescribed based on the skin type of the patient according to Fitzpatrick (Astner S., Anderson RR, 2004). Moreover, in patients with a skin phototype I and II, UVA irradiation is carried out in the following dose range: 0.5-1.0-1.5-2.0-2.5-3.0 J / cm ² . In patients with type III and type IV skin, UVA doses are increased according to the following scheme: 0.6-1.2-1.8-2.4-3.0-3.6 J / cm ² . When treating with PUVA baths, the initial dose of UVA exposure is 25-30% of the minimum phototoxic dose (MFD) for patients with I and II phototype of the skin, 30-40% of MFD for patients with III and IV phototype. Procedures are carried out every other day, 3 times a week. A single dose of each subsequent procedure increases by 25-30% of MFD.

The corticosteroid hormone - prednisone was administered orally in patients with fungoid mycosis in an adaptive dose of 0.3 mg / kg / day for 15-20 days, then when the clinical stabilization of the process was achieved, the daily dose was reduced by 2.5 mg in 3 days. Against the background of glucocorticosteroid therapy, the introduction of integral was carried out intramuscularly.

In accordance with the general recommendations for the use of interal, the preparation was administered intramuscularly with 1 million IU of the active substance dissolved “ex tempore” in 1.0 ml of water for injection. Interal patients were prescribed from 1 week of therapy and were administered every other day, a total of 10 injections of the drug per course.

PUVA baths with 0.3% amifurin solution were performed every other day, 3 times a week, with a total course of 10 sessions.

Treatment was carried out under the control of a hemogram 1 time in 7 days.

The duration of treatment for patients with fungoid mycosis was 21-25 bed days.

When evaluating the clinical effectiveness of the proposed method for the treatment of patients with fungoid mycosis, the following criteria were taken into account:

1) a change in subjective sensations (reduction or disappearance of itching, dryness and peeling of the skin);

2) the dynamics of objective clinical manifestations (color change, decrease in infiltration of morphological elements);

3) general condition (temperature, blood pressure, pulse, clinical blood tests, urine tests, including biochemical and immunological blood tests).

Positive clinical dynamics, as a rule, began already in the first 7 days of therapy and was expressed in a decrease in hyperemia and infiltration in the foci, a decrease in the intensity of itching and burning of the skin. By the end of the course of intramuscular administration of interal and PUVA baths, a steady regression of symptoms was observed: the state of erythroderma was practically resolved, infiltrative-plaque rashes flattened, spotted manifestations disappeared, often leaving hyperpigmented skin areas.

The use of the proposed method for the treatment of patients with fungoid mycosis is illustrated by the following examples:

Example 1: Patient L., 69 years old, has been under observation at the clinic of the Federal State Institution of UrNIIDViI since 2008, after repeated histological studies in 2009, the diagnosis was verified: T-cell malignant lymphoma of the skin. Mushroom mycosis, stage IIA. The patient repeatedly underwent inpatient treatment in the clinic, using desensitizing, detoxifying drugs, systemic therapy (prednisone 30 mg / day for 14-20 days) and external corticosteroid therapy, was prescribed with an improvement in maintenance therapy with glucocorticosteroids. The skin process has become resistant to the therapy, frequent exacerbations were combined with short periods of remission (from 2 to 3 months).

Clinical and laboratory studies at the Federal State Institution UrNIIDViI revealed dysimmunoglobulinemia and an increase in IgE in the immunogram. In the peripheral blood - moderate leukocytosis, lymphocytosis.

The patient was prescribed treatment with interal according to the scheme in the form of intramuscular injections of 1 million ME of the active substance - interal, dissolved "ex tempore" in 1.0 ml of water for injection. Interal was administered every other day, for a total of 10 injections of the drug. At the same time, prednisone per os 15 mg / day (0.3 mg / kg / day) was prescribed for 15 days, antihistamines, external ointment therapy. From 1 week of therapy, PUVA baths with 0.3% ammifurin solution every other day, 3 times a week, with a general course of 10 were prescribed. Treatment was carried out under the control of a hemogram 1 time in 7 days.

As a result of the therapy, after 4 injections of the integral drug and the 3rd session of the PUVA baths (2 weeks of treatment), the patient noted a decrease in active hyperemia and infiltration in the plaque area, a decrease in the intensity of itching and peeling in the rash. After 10 injections of the drug and completion of the PUVA bath, spotted skin rashes almost regressed, and plaques significantly decreased in height, the itching completely disappeared. At discharge (the total length of hospital stay is 24 days), the process regressed by 50%, which characterized the outcome of therapy as a partial remission of the process.

Adverse reactions and complications during therapy were not noted. A dynamic study of immunological status revealed a downward trend in IgE and peripheral blood leukocytosis.

Example 2: Patient P., 60 years. He entered the Department of Dermatology with complaints of rashes on the skin of the trunk and extremities, constant intense skin itching and burning. He has been ill with this disease for 17 years; over the previous 2 years, he has noted a continuously recurring course of the disease, despite the ongoing therapy (desensitizing, detoxifying, prednisolone per os 40 mg / day, topical corticosteroids). Histological examination and immunophenotyping of a skin sample made it possible to establish a diagnosis of T-cell malignant lymphoma of the skin. Mushroom mycosis, erythrodermic form (stage III).

The general condition at the time of admission was assessed as satisfactory, respiration in the lungs was vesicular, wheezing was not heard, heart sounds were rhythmic, blood pressure was 140/80 mm Hg, pulse was 78 beats per minute. The liver is not enlarged, the spleen is not palpable.

Upon examination of the patient - the skin is in a state of total erythroderma, the skin is brick red with a bluish tint, with severe infiltration. The skin is dry, with painful cracks in the places of physiological folds of the skin, with small-scaled peeling, linear excoriation with hemorrhagic crusts is present on the skin of the trunk and upper limbs. On the skin of the palms and soles - the phenomenon of hyperkeratosis.

Somatic: GB II Art., NK 0-1. Chronic bronchitis, remission.

Clinical and laboratory studies in the in-patient department of the URNIIDViI revealed abnormalities in the main immunological parameters: violation of the ratio of the T-helper / T-suppressor populations, disimmunoglobulinemia, 10.2-fold increase in the content of IgE (1114.0 IU / ml) in blood serum . In the peripheral blood - leukocytosis (11.2 × 10 ⁹ / l), lymphocytopenia (21.0%), eosinophilia, an increase in ESR up to 22 mm / hour. The biochemical analysis of blood revealed hypoproteinemia (50.4 g / l) and hypoalbuminemia (30.0%).

The patient was prescribed treatment with interal according to the above scheme in the form of intramuscular injections of 1 million IU of the active substance — interal dissolved in ex tempore in 1.0 ml of water for injection. Interal was administered every other day, for a total of 10 injections of the drug. At the same time, prednisone 25 mg / day per os (0.3 mg / kg / day) was prescribed for 20 days, antihistamines, external ointment therapy. From 1 week of therapy, PUVA baths with 0.3% ammifurin solution every other day, 3 times a week, with a total course of 10 sessions, were prescribed.

As a result of the therapy, after 3 injections of the drug Integral (1 week of treatment), a significant decrease in the intensity of itching and burning was noted; after 4 injections (2 weeks of treatment), a decrease in hyperemia and peeling of the skin was recorded, and skin infiltration and peeling significantly decreased during the same period. The resolution of erythrodermic manifestations occurred on the 23rd day of full-dose therapy, at the time of completion of the integral injections and the course of the PUVA baths.

The treatment was carried out under the control of a hemogram 1 time in 5 days. Adverse reactions and complications of the therapy were not observed.

In the repeated immunogram after the course of therapy, a significant decrease in the level of IgE (370.6 IU / ml) was observed, approaching the normal values of the ratio of T-helper / T-suppressor populations. In peripheral blood - normalization of the content of leukocytes, lymphocytes and ESR.

The duration of the inpatient treatment course was 25 days, there were no adverse reactions and complications of therapy, the patient was discharged from the clinic in a state of complete clinical remission. It is recommended that a dermatologist observe a gradual decrease in the daily dose of prednisolone per os by 2.5 mg in 3 days. Against the background of the daily intake of a maintenance dose of prednisone 3 tablets per day (15 mg), the appearance of new elements in the patient is not observed for 7 months.

The proposed method in the Department of Dermatology treated 11 patients with GM (5 women and 6 men) aged 51 to 69 years (average age 59.1 ± 6.4 years), with I and II skin phototypes, 4 of which were in a state of erythroderma (according to the classification of TNM - stage III of the development of GM) and 7 patients - with stage IIA GM. The duration of the disease ranged from 2.5 to 17 years. The diagnoses were histologically verified at the clinic of the Federal State Institution UrNIIDViI of the Russian Medical Technologies. Previously, patients were treated using systemic and topical corticosteroids, which made it possible to achieve short-term clinical remission from 2 to 5 months. Anamnestically and clinically patients of this group were distinguished by frequent exacerbations of the process (from 3 to 4 episodes per year), the rapid development of erythroderma, accompanied by the occurrence of pyogenic complications on the skin, and the presence of a concomitant pathology of inflammatory systems and organs.

After a course of therapy by the claimed method, the state of clinical improvement was achieved in all patients (100%), of which 8 (72.7%) patients had clinical remission. The duration of remission for the observed period ranged from 3 to 14 months.

The properties achieved by the application of this invention are shown in tables 1-3.

Compared with the prototype, the claimed treatment method allows us to significantly increase the effectiveness of therapy for patients with fungoid mycosis. So, from the data of table 1 it can be seen that the described method of treatment does not lead to the progression of the process in any patient with fungoid mycosis. In all patients, after the end of therapy, clinical improvement was achieved: in 3 (27.3%) patients - partial, and in 8 (72.7%) patients - complete remission of the disease. In addition, side effects from the therapy were significantly less common in patients compared with the prototype. When treating patients with the claimed method, side effects were recorded only in 1 (9.1%) patient, consisting in a short-term increase in body temperature to 39.0 ° C and increased intensity of skin itching. These clinical symptoms in the patient were noted after the first injection of integral and were of a single character, which did not require further discontinuation of the drug.

At the same time, the prototype method of treating patients with fungoid mycosis, which consists in conducting only PUVA baths with a photosensitizer, showed lower clinical efficacy results. Thus, complete clinical remission was achieved only in 3 (19.0%) of 16 patients, and partial clinical remission was recorded in 13 (81.0%) patients. At the same time, in the course of therapy, adverse phototoxic effects were noted in 3 (19.0%) patients with GM.

Table 2 shows their own clinical efficacy data of the modified method for the treatment of patients with fungoid mycosis in comparison with the data of the prototype.

In total PUVA baths with methoxypsoralen (prototype of the invention) were performed in 16 patients with fungoid mycosis. To achieve clinical improvement in patients, 29.4 ± 1.4 sessions of PUVA baths were required, with an average cumulative course dose of UVA of 33.3 ± 3.3 J / cm ² . At the same time, our proposed method for the treatment of patients with fungoid mycosis demonstrated high clinical efficacy even after 10 sessions of PUVA baths, and a decrease in the average cumulative radiation load (23.8 ± 0.4 J / cm ² ) 1.4 times lower. than the prototype, and the absence of side effects.

The duration of inpatient treatment required to achieve clinical improvement in patients with GM treated by the claimed method averaged 22.3 ± 3.7 days, which was 2.8 times less than the duration of treatment of patients with the other method described in the prototype (63.1 ± 3.5 days).

The duration of clinical remission in patients with fungoid mycosis treated with PUVA baths and intramuscular injections of interal averaged 7.3 months (Table 3).

Thus, our proposed method for the treatment of patients with fungoid mycosis, which consists in the use of prednisone and integral in biologically adequate dosages, in combination with PUVA baths with 0.3% ammifurine solution, significantly exceeds the therapy efficacy data presented in the prototype, which allows achieving clinical improvement in patients with lower cumulative course doses of UVA, which reduces the risk of side effects and reduces the duration of inpatient treatment.

Table 1
Clinical efficacy of treatment of patients with T-ZLK (GM) Sick Clinical form and stage The effectiveness of the therapy Side effects PP CR ETC Own data L-x, 69 l. GM, stage II - + - - S, 55 l. GM, stage II - - + - Zs, 51 g. GM, stage II - - + subfebrile condition, increased itching K-in, 66 liters. GM, stage III - - + - Peninsula, 60 liters. GM, stage III - - + - K-a, 52 g. GM, stage II - - + - Za, 57 l. GM, stage II - - + - Island 51 GM, stage II - - + - K-n, 67 l. GM, stage III - + - - K-n, 60 l. GM, stage III - + - - B-in, 62 g. GM, stage II - - + - Total: 11 patients 0 3 (27.3%) 8 (72.7%) 1 (9.1%) * Data F.Weber, M.Schmuth, N.Sepp et al. (2005) Total: 16 patients 0 13 (81.0%) 3 (19.0%) 3 (19.0%) * * - side effects are described PZ - disease progression CR - partial remission PR - complete remission

table 2
Comparison of clinical efficacy indicators of a new method of treating patients with fungoid mycosis with data on the prototype Indicators Data F.Weber, M.Schmuth, N.Sepp et al., 2005 (n = 16) Own data, 2010 (n = 11) Number of PUVA therapy sessions 29.4 ± 1.4 10* The average cumulative dose of UVA (J / cm ² ) 33.3 ± 3.3 23.8 ± 0.4 * The presence of complications from therapy 3 (19.0%) 1 (9.1%) Duration of inpatient treatment (days) 63.1 ± 3.5 22.3 ± 3.7 • - p <0.05 when comparing between groups of patients

Table 3 Comparative data on the duration of remission after treatment by the claimed method in patients with fungoid mycosis. Sick Clinical characteristics of patients Results after previously applied other treatments Results after therapy of the claimed method The frequency of exacerbations per year Duration of remission (months) The frequency of exacerbations per year Duration of remission (months) L-x, 69 l. GM, stage II 3 3 2 5 S, 55 l. GM, stage II 2 four one 8 Zs, 51 g. GM, stage II Continuously relapsing 0 3 3 K-in, 66 liters. GM, stage III 3 3 2 four Peninsula, 60 liters. GM, stage III Continuously relapsing 0 one 7 K-a, 52 g. GM, stage II one eleven 0 13 Za, 57 l. GM, stage II 2 3 2 5 Island 51 GM, stage II 2 8 0 fourteen K-n, 67 l. GM, stage III Continuously relapsing 0 2 5 K-n, 60 l. GM, stage III 3 four one 9 B-in, 62 g. GM, stage II 2 four one 8

Claims (1)

A method of treating patients with fungoid mycosis by performing PUVA baths with a photosensitizer solution 3 times a week, characterized in that, additionally, simultaneously with PUVA baths against the background of symptomatic therapy: antihistamines, external ointment therapy, oral prednisolone corticosteroid hormone is prescribed orally in an adaptive dose of 0, 3 mg / kg / day for 15-20 days and 10 intramuscular injections of an immunomodulator - integral of 1 million ME every other day, and PUVA baths are carried out in a general course of 10 sessions.