RU2491954C2 - Method of treating lichen ruber planus of oral cavity mucosa - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to dermatology and dentistry, and can be applied for treatment of lichen ruber planus of oral cavity mucosa. For this purpose at the background of traditional therapy applied is combination of two medications immunomax and gepon. Immunomax is introduced intramuscularly in dose 200 U, one time per day on 1, 2, 3, 8, 9 and 10-th days of treatment. Gepon is applied by irrigation of affected areas of oral cavity mucosa with 0.04% solution, daily during the entire treatment course.

EFFECT: method makes it possible to achieve high efficiency of treatment and contributes both to correction of immune disorders and local manifestations of disease on oral cavity mucosa.

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Description

The invention relates to medicine, namely to dermatology and dentistry, and can be used to treat lichen planus of the oral mucosa.

The prototype of the invention is the method described in patent RU 2367445 C1 from 09/20/2009, in which N.N. Filimonkova, O.V. Letaeva provides a method for the complex treatment of lichen planus using the drug Panavir intravenously at 200 mcg every other day. The described method provides an increase in the effectiveness of treatment of lichen planus, the absence of side effects and an increase in the timing of remission.

The disadvantages of this method is the presence of pathogenetically substantiated treatment of only skin manifestations of lichen planus. The prototype does not describe the possibility of effective treatment of manifestations of lichen planus on the oral mucosa, and the invention justified the feasibility of using immunotropic drugs for the treatment of manifestations on the oral mucosa with lichen planus.

The technical result is the development of a method for improving the treatment of lichen planus of the oral mucosa by correcting the immunological reactivity of the patient’s body.

The technical result is achieved by the fact that for the treatment of lichen planus of the oral mucosa, the preparation Immunomax (Immafarma LLC) is used by intramuscular injection of 200 units once a day on the 1st, 2nd, 3rd, 8th, 9th and 10th days of treatment and the preparation gepon (Immafarma LLC) by irrigation with a 0.04% solution of the affected areas of the mucosa (the contents of the vial are dissolved in 5 ml of water for injection).

The invention is illustrated in the drawing.

The drawing shows a graphical depiction of shifts of laboratory parameters for various forms of lichen planus of the oral mucosa after immunocorrection with immunomax and gepon in comparison with shifts with standard treatment, justifying the appropriateness of our treatment regimen.

The following symbols are used in the drawing:

L - white blood cells; ESR - erythrocyte sedimentation rate; CEC - circulating immune complexes; E - eosinophils; CD20 - B - lymphocytes; CD3 - T - lymphocytes; CD4 - T - helpers; CD8 - cytotoxic and suppressor T - lymphocytes; Ig G - immunoglobulin G; Ig A - immunoglobulin A; Ig M - immunoglobulin M; Lys - lysozyme; IHL - data of luminol-dependent chemiluminescence.

The method is carried out by applying for the treatment of lichen planus of the oral mucosa against the background of the traditional therapy of the drug Immunomax (Immafarma) using intramuscular injections of 200 units once a day on the 1st, 2nd, 3rd, 8th, 9th and 10th days of treatment and the use of a hepone preparation (Immafarma) by irrigation with a 0.04% solution of affected skin areas, for which the contents of the vial are dissolved in 5 ml of water for injection.

The method is confirmed by the results of a study conducted in 2007-2009 in the clinic of the Department of Dermatovenerology and Dentistry of the Kursk State Medical University, in which reliable data were obtained confirming the effectiveness of an integrated approach to the treatment of lichen planus of the oral mucosa, providing for the impact on one of the main etiopathogenetic links of the disease - correction of the immunological reactivity of the patient.

We examined 136 patients with lichen planus of the oral mucosa with the following clinical varieties:

1) a typical form - 44% of patients;

2) exudative-hyperemic form - 20% of patients;

3) erosive-ulcerative form - 36% of patients.

All patients were divided into two groups, randomized by gender, age, concomitant pathology, type of damage to the oral mucosa. The main group (n = 86), in combination with traditional treatment, received immunomodulators immunomax and gepon. To compare the effectiveness of treatment, the second group (comparison group) (n = 50) received a similar traditional treatment, but without the use of immunocorrection. In both groups, a unified system of cumulative clinical assessment and the same criteria for evaluating treatment outcomes were used.

Immunomax is one of the most active immunomodulators among injectable drugs that stimulates the healing of ulcerative lesions. A feature of gepon is good absorption on the mucous membranes, especially in the oral cavity, including on the surface of erosion and ulcers. Therefore, the drug can be taken in the form of irrigation. Gepon activates not only the general immune defense of the body, it also activates local defense systems. Due to this action, we used gepon to treat manifestations of lichen planus on the oral mucosa.

The sterile preparation Immunomax - lyophilized powder of 200 DB in injection bottles is manufactured by Immafarma LLC. We prescribed intramuscular injections of Immunomax 200 units once a day on the 1st, 2nd, 3rd, 8th, 9th and 10th days of treatment. Before use, the contents of the vial (ampoule) are dissolved in 1 ml of water for injection, injected intramuscularly at 200 units. The mucous membranes were irrigated with a 0.04% hepone solution. Before use, the powder was dissolved in 5 ml of water for injection or saline.

In addition, we conducted a study of the general analysis of blood, immunological parameters, lysozyme index. The functional activity of neutrophils in the blood serum of patients was evaluated by the method of induced luminol-dependent chemiluminescence (IPL) induced by opsonized zymosan. We obtained data presented depending on the form of damage to the oral mucosa in tables 1, 2 and 3.

Table 1 The average laboratory values in the group of patients with a typical form of lichen planus before and after treatment №№ p.p. Indicator Before treatment M ± m main group M ± m Shift,% comparison group M ± m Shift,% one White blood cells × 10 ^ 9 / L 11.46 ± 0.24 6.01 ± 0.15 -48 7.61 ± 0.30 -34 2 Eosinophils,% 1.59 ± 0.18 0.68 ± 0.13 -57 1.38 ± 0.24 -13* 3 ESR, mm / h 12.14 ± 0.37 3.98 ± 0.31 -67 7.51 ± 0.64 -38 four CD3 + T-lymphocytes,% 51.82 ± 0.29 68.53 ± 0.39 +32 63.98 ± 0.95 +23 5 CD4 + T-lymphocytes,% 27.64 ± 0.46 35.45 ± 0.35 +28 32.49 ± 0.63 +18 6 CD8 + T-lymphocytes,% 36.74 ± 0.20 29.40 ± 0.33 -twenty 29.82 ± 0.69 -19 7 CD20 + T-lymphocytes,% 14.64 ± 0.24 14.43 ± 0.27 -one* 13.98 ± 0.22 -5 8 Ig G, g / l 18.30 ± 0.30 9.92 ± 0.30 -46 11.57 ± 0.84 -37 9 Ig M, g / l 2.37 ± 0.04 2.10 ± 0.03 -eleven 2.14 ± 0.03 -10 10 Ig A, g / l 4.37 ± 0.12 3.03 ± 0.44 -31 3.16 ± 0.18 -28 eleven CEC, conv. units 56.60 ± 0.88 42.45 ± 0.48 -25 50.73 ± 1.06 -10 12 Lysozyme (mcg / ml) 3.10 ± 0.82 4.76 ± 1.01 +54 3.30 ± 0.96 +6 13 IHL 17.65 ± 1.30 11.50 ± 2.13 -35 15.40 ± 1.26 -13 fifteen Σ shifts,% 455 254 Note: 1. * - statistically insignificant shifts; 2. the reliability of the results of the study of statistically significant data p≤0,05; 3. M ± m - the average value of the indicator; 4. shift,% - change in the average value of the indicator in comparison with its value before treatment; 5. Σ shifts,% - the sum of the shifts without taking into account the sign of the shift.

table 2 The average values of laboratory parameters in the group of patients with exudative-hyperemic form of lichen planus before and after treatment №№ p.p. Indicator Before treatment M ± m main group M ± m Shift,% comparison group M ± m Shift,% one White blood cells × 10 ^ 9 / L 12.46 ± 0.24 7.01 ± 0.15 -44 8.84 ± 0.30 -23 2 Eosinophils,% 1.99 ± 0.18 0.90 ± 0.13 -55 1.90 ± 0.24 + 19 * 3 ESR, mm / h 13.12 ± 0.37 4.18 ± 0.31 -68 9.51 ± 0.64 -22 four CD3 + T-lymphocytes,% 50.82 ± 0.29 69.13 ± 0.39 +36 62.18 ± 0.95 +20 5 CD4 + T-lymphocytes,% 26.65 ± 0.46 34.45 ± 0.35 +29 30.49 ± 0.63 +10 6 CD8 + T-lymphocytes,% 38.74 ± 0.20 29.90 ± 0.33 -23 34.82 ± 0.69 -5 7 CD20 + T-lymphocytes,% 14.14 ± 0.24 14.47 ± 0.27 + 2 * 13.48 ± 0.22 -8 8 Ig G, g / l 19.30 ± 0.30 9.96 ± 0.30 -48 15.77 ± 0.84 -fourteen 9 Ig M, g / l 2.17 ± 0.04 2.11 ± 0.03 -3 2.14 ± 0.03 -10 10 Ig A, g / l 5.37 ± 0.12 3.03 ± 0.44 -44 5.86 ± 0.18 +34 eleven CEC, conv. units 57.60 ± 0.88 46.45 ± 0.48 -19 51.73 ± 1.06 -9 12 Lysozyme (mcg / ml) 2.30 ± 0.82 4.30 ± 1.01 +87 2.70 ± 0.96 +17 13 IHL 28.37 ± 1.30 13.50 ± 2.13 -52 21.40 ± 1.26 -25 fifteen Σ shifts,% 510 216 Note: 1. * - statistically insignificant shifts; 2. the reliability of the results of the study of statistically significant data p≤0,05; 3. M ± m - the average value of the indicator; 4. shift,% - change in the average value of the indicator in comparison with its value before treatment; 5. Σ shifts,% - the sum of the shifts without taking into account the sign of the shift.

Table 3 The average values of laboratory parameters in the group of patients with erosive-ulcerative form of lichen planus before and after treatment №№ p.p. Indicator Before treatment M ± m main group M ± m Shift,% comparison group M ± m Shift,% one White blood cells × 10 ^ 9 / L 12.48 ± 0.24 5.01 ± 0.15 -60 9.61 ± 0.30 -16 2 Eosinophils,% 2.19 ± 0.18 0.90 ± 0.13 -59 1.39 ± 0.24 -13* 3 ESR, mm / h 14.12 ± 0.37 4.98 ± 0.31 -65 8.55 ± 0.64 -thirty four CD3 + T-lymphocytes,% 52.82 ± 0.29 64.53 ± 0.39 +22 62.48 ± 0.95 +21 5 CD4 + T-lymphocytes,% 28.63 ± 0.46 34.45 ± 0.35 +20 30.48 ± 0.63 +10 6 CD8 + T-lymphocytes,% 36.30 ± 0.20 29.60 ± 0.33 -eighteen 28.82 ± 0.69 -22 7 CD20 + T-lymphocytes,% 14.54 ± 0.24 14.13 ± 0.21 -3 - 13.93 ± 0.92 -5 8 Ig G, g / l 19.30 ± 0.30 9.32 ± 0.30 -52 11.17 ± 0.84 -39 9 Ig M, g / l 2.37 ± 0.04 2.10 ± 0.03 -eleven 2.14 ± 0.03 -10 10 Ig A, g / l 4.30 ± 0.12 3.01 ± 0.44 -thirty 3.76 ± 0.18 -fourteen eleven CEC, conv. units 58.60 ± 0.88 46.45 ± 0.48 -21 53.73 ± 1.56 -5 12 Lysozyme (mcg / ml) 2.06 ± 0.82 4.09 ± 1.01 +99 2.90 ± 0.96 +41 13 IHL 48.47 ± 1.30 12.90 ± 2.13 -73 30.40 ± 1.26 -37 fifteen Σ shifts,% 533 263 Note: 1. * - statistically insignificant shifts; 2. the reliability of the results of the study of statistically significant data p≤0,05; 3. M ± m - the average value of the indicator; 4. shift,% - change in the average value of the indicator in comparison with its value before treatment; 5. Σ shifts,% - the sum of the shifts without taking into account the sign of the shift.

It should be noted that with the aggravation of the clinical form, laboratory data are transformed towards the inflammation process, which is typical for these stages and forms of the disease. Strengthening of inflammatory and destructive processes in the epithelium of the oral mucosa with lichen planus is accompanied by intrapopulation rearrangement of the T-cell immunity. A study of the state of cellular immunity showed that in patients with lichen planus with lesions of the oral mucosa in the circulating blood, the relative content of T-lymphocytes is reduced. In the analysis of immunoregulatory subpopulations of T-lymphocytes (CD4 and CD8) in the vast majority of cases, a combination of deficiency of CD4 T-lymphocytes with an increased, compared to healthy, content of CD8 T-lymphocytes was noted. The number of CD20 cells in patients practically did not differ from this indicator in healthy patients. Thus, the results of our study confirm the presence of changes in the cellular immunity in patients with lichen planus. As shown by the results of a study of the content of immunoglobulins of the main classes (Ig A, Ig M, Ig G), pathological disorders are also observed in patients with lichen planus in the humoral immunity link. They observed hyperproduction of Ig G, a slight increase in the content of Ig M in comparison with healthy ones, and an increase in the function of complexation in the immune system was also observed. It should be noted that the proven pathogenetic role of circulating immune complexes lies not only in the ability to directly cause tissue damage, but also to stimulate many of the humoral and cellular systems of the body, which leads to the overproduction of biologically active substances that are also involved in tissue damage processes. Shifts in humoral immunity are also characterized by a decrease in the level of Ig A, which affects the mechanisms of local immunity. Thus, the results of our study confirm a significant imbalance in the activity of the immune system at the level of both the cellular and humoral link in patients with lichen planus.

In patients of the main group receiving immunocorrection, the number of leukocytes, eosinophils, and ESR was normalized. The positive trend of changes in these indicators in patients receiving traditional therapy was not so pronounced. A study of the state of cellular immunity showed that in patients receiving immunomax and hepone, the relative content of CD3 T-lymphocytes in the circulating blood normalized to a greater extent than in the group treated with the traditional method. In the analysis of immunoregulatory subpopulations of T-lymphocytes (CD4 + and CD8 +) in the vast majority of cases in the first group we noted a combination of a significant increase in the CD4 + population and a decrease in the content of CD8 +. As shown by the results of studying the content of immunoglobulins of the main classes (Ig A, Ig M, IgG) and circulating immune complexes, in patients with red lichen planus, the deviations in the humoral immunity link also decreased.

Thus, the combined use of these immunomodulators in various forms of lichen planus of the oral mucosa has a corrective effect on T-lymphocytes and provides greater clinical efficacy of therapy than standard therapy.

The functional activity of neutrophils in the blood serum of patients with lichen planus of the oral mucosa was judged by their oxygen metabolism. We analyzed the data obtained during the study of the luminol-dependent chemiluminescence (IHL) induced by the opsonized zymosan-induced zymosan. We noted an increase in the rate of formation of active forms of oxygen radicals by neutrophils as inflammatory-destructive processes in the epithelium increase with lichen planus, which is a reflection of the severity of the inflammatory process.

The study of one of the important factors of nonspecific resistance of the lysozyme organism is essential. In all patients with lichen planus of the oral cavity, a deficiency of endogenous lysozyme was revealed, which worsens as the inflammatory and destructive processes in the epithelium progress.

In the process of treatment, a tendency to an increase in the level of endogenous lysozyme was noted; in patients with typical, exudative-hyperemic and erosive-ulcerative forms, he reached physiological norm values. Assessment of the functional state of peripheral blood neutrophils in patients with lichen planus of the oral cavity showed that their average values in all clinical forms decreased compared to the initial ones.

The results of the immunocorrection course indicate a positive clinical effect, which can be judged by the timing of remission for various clinical forms of lichen planus. In patients with a typical form, the remission period was extended to 11.4 ± 1.3 months, with exudative-hyperemic - up to 9.3 ± 1.2 months, with erosive-ulcerative - 7.4 ± 1.7 months. With exudative-hyperemic form, the rapid disappearance of hyperemia, a decrease in the area of papular rashes are noted. The erosion surface was cleaned, erosion was epithelized within 10-15 days. Patients noted an improvement in general condition, a decrease and in some cases the disappearance of subjective complaints of discomfort, burning, tightness, pain. For a more severe form - erosive-ulcerative - was characterized by a change in the mucous membrane of the oral cavity, which acquired the usual color and appearance; exudation, swelling, congestive hyperemic background leveled. The process of transformation of clinical forms into less severe ones was observed.

Having received the positive dynamics of the course of all forms of lichen planus of the oral mucosa with the use of immunomax and hepone, we have developed treatment regimens for the disease using these immunomodulators.

Case Study

Patient M., 45 years old, medical history No. 768, was admitted to the hospital for treatment of Kursk OKVD on March 12, 2008 with a diagnosis of lichen planus with lesions of the oral mucosa of an erosive-ulcerative form. Sick for 2 years. There are no concomitant diseases in the acute phase. The diagnosis is confirmed by objective research.

The values of laboratory parameters: the total number of leukocytes 14.3 × 10 ⁹ ; the number of eosinophils 2%; ESR 17 mm / h; CD3 54%; CD4 33%; CD8 28%; CD20 14%; serum IgG concentration of 21.6 g / l; IgM 2.33 g / l; IgA 5.84 g / l; the number of circulating immune complexes (CEC) 68 usled

Against the background of traditional therapy, the patient received the preparation Immunomax (Immafarma LLC) using intramuscular injections of 200 units once a day on the 1st, 2nd, 3rd, 8th, 9th and 10th days of treatment and use of the hepone preparation (Immafarma) by irrigation with a 0.04% solution of the affected areas of the mucosa, for which the contents of the vial are dissolved in 5 ml of water for injection.

On the 15th day of treatment, the oral mucosa acquired the usual color and appearance; exudation and swelling have completely disappeared. The values of laboratory parameters after therapy: the total number of leukocytes 6.3 × 10 ⁹ ; the number of eosinophils 0%; ESR 8 mm / h; CD3 48%; CD4 23%; CD8 39%; CD20 14.1%; the concentration of serum IgG 2.6 g / l; IgM 2.03 g / l; IgA 2.84 g / l; the number of circulating immune complexes (CEC) 10 srvc

Thus, the task has been achieved through the use of immunocorrective preparations of immunomax and gepon.

Application of the developed method allows to solve a number of problems:

1. Achieving high efficiency in the treatment of manifestations on the oral mucosa with lichen planus.

2. Correction of immune disorders in patients with lichen planus of the oral mucosa.

Claims (1)

A method of treating lichen planus of the oral mucosa, characterized in that against the background of traditional therapy, a combination of two drugs is used: immunomax intramuscularly at 200 units once a day for 1, 2, 3, 8, 9 and 10 days of treatment and gepon by irrigation with a 0.04% solution of the affected areas of the oral mucosa, daily during the entire course of treatment.

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