RU2449806C1 - Method of treating lichen acuminatus of oral mucosa - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method relates to medicine, particularly to dermatology and dentistry, and may be applied in treating lichen acuminatus of oral mucosa. That is ensured by oral irrigations with 0.04 % Hepon followed by applications of 0.04 % Hepon wipes on the affected skin for 30 minutes once a day for ten days; the method is characterised by a favourable effect on reparative and effective immune corrective processes manifested in the patients.

EFFECT: mode of using Hepon effective treatment of various forms of lichen acuminatus ensured by reduced inflammation and activated local immunity.

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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 No. 2285816 C1 dated 08/20/2005, in which S.V. Kungurov, V.I. Prokhorenkov, A.S. Solntsev and I.N.Bolshakov provide a method for treating the oral mucosa with lichen planus. The method consists in local application of a hormonal agent to the oral mucosa, as well as a keratoplastic agent in the form of a chitosan solution, with continued treatment with said chitosan solution 1 time per day after meals and 1 time at night, also for 30 days.

The disadvantages of this method is the use of a hormonal drug without taking into account the pathogenetic links in the occurrence of this pathology, as well as the significant duration of therapy (more than 30 days). The prototype does not describe a change in immune status, but the invention justifies the feasibility of affecting one of the main etiopathogenetic links of the disease - a violation of the immunological reactivity of the patient, in addition, the method described in the invention has a pronounced anti-inflammatory effect on the mucosa, which manifests itself in the first 1- 2 days after the use of the drug and leads to the rapid elimination of the main symptoms and the acceleration of reparative processes.

The objective of the invention is to develop a method for improving the treatment of lichen planus of the oral mucosa by correcting the immunological reactivity of the patient's body.

This object is achieved in that for the treatment of lichen planus of the oral mucosa, the drug hepone (Immafarma LLC) is used by irrigation of the mucous membranes of the oral cavity with a 0.04% hepone solution (single dose of 0.002 g), followed by the application of gauze napkins on the inflamed areas of the skin. moistened with a 0.04% hepone solution (single dose of 0.002 g) for 30 minutes. Before using the drug, the mucous membrane is irrigated with saline. Procedures are performed once a day, for a course of 10 procedures.

The method is carried out by irrigation of the mucous membranes of the oral cavity with a 0.04% hepone solution (single dose of 0.002 g) for which the contents of the vial are dissolved in 5 ml of water for injection; followed by applying gauze napkins moistened with a 0.04% hepone solution (single dose of 0.002 g) to the inflamed areas of the skin for 30 minutes. Before using the drug, the mucous membrane is irrigated with saline. Procedures are performed once a day, for a course of 10 procedures.

The method is confirmed by the results of a study conducted during 2007-2009. in the clinic of the departments 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 correction of the immunological reactivity of the patient.

We examined 76 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 = 36), in combination with traditional treatment, received a hepon immunomodulator. To compare the effectiveness of treatment, patients of the second group (comparison group) (n = 40) 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.

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 mucous membranes were irrigated with a 0.04% solution of hepone (a single dose of 0.002 g), for which the contents of the vial were dissolved in 5 ml of water for injection; followed by applying gauze napkins moistened with a 0.04% hepone solution (single dose of 0.002 g) to the inflamed areas of the skin for 30 minutes. The procedures were performed 1 time per day, for a course of 10 procedures.

The study used material (saliva and oral fluid) obtained from patients and 40 healthy individuals. The state of local immunity of the oral cavity was evaluated using cytological methods (determination of the content of cellular elements in the liquid of the periodontal pocket). The results are presented in tables 1 and 2.

Table 1 Cell composition and activity of phagocytic cells of the contents of the gingival pocket of patients with lichen planus before treatment Indicators Healthy Typical Exudative-hyperemic Erosive and ulcerative Standard therapy Gepon Standard therapy Gepon Standard therapy Gepon Cell Nuclei (%) 4.2 ± 0.3 9.7 ± 1.0 * 9.57 ± 1.3 * 14.0 ± 1.5 * 13.0 ± 1.3 * 16.0 ± 1.5 * 16.2 ± 1.4 * Destroyed cells (%) 4.1 ± 0.7 19.0 ± 2.0 * 18.9 ± 1.2 * 20.5 ± 2.2 * 21.8 ± 2.0 * 28.8 ± 0.2 * 29.6 ± 0.8 * Epithelial cells (%) 78.4 ± 1.3 16.5 ± 1.5 * 18.9 ± 1.3 * 16.0 ± 1.5 * 16.4 ± 1.2 * 17.0 ± 1.5 * 17.4 ± 1.1 * Polymorphic nuclear leukocytes (%) 17.6 ± 0.3 77.0 ± 1.3 * 81.7 ± 2.1 * 69.0 ± 1.0 * 70.7 ± 2.3 * 73.0 ± 1.3 * 74.1 ± 1.5 * Mononuclear leukocytes (%) 3.1 ± 0.2 6.5 ± 1.4 * 7.1 ± 0.9 * 15.0 ± 2.2 * 15.9 ± 1.8 * 16.0 ± 1.8 * 16.2 ± 1.9 * The differences in the indicators in the groups are significant at p <0.05: from the norm *.

table 2 The cell composition and activity of phagocytic cells of the contents of the gingival pocket of patients with lichen planus after treatment Indicators Healthy Typical Exudative-hyperemic Erosive and ulcerative Standard therapy Gepon Standard therapy Gepon Standard therapy Gepon Cell Nuclei (%) 4.2 ± 0.3 16.0 ± 0.9 * 6.3 ± 0.7 *, ** 17.5 ± 0.6 * 7.9 ± 0.5 *, ** 15.5 ± 0.6 * 9.6 ± 1.1 *, ** Destroyed cells (%) 4.1 ± 0.7 10.1 ± 1.4 * 6.5 ± 1.3 *, ** 11.7 ± 1.1 * 7.8 ± 1.2 *, ** 10.7 ± 1.2 * 8.7 ± 1.4 *, ** Epithelial cells (%) 78.4 ± 1.3 45.1 ± 1.7 * 68.9 ± 2.1 *, ** 44.2 ± 2.2 * 65.3 ± 2.2 *, ** 48.0 ± 1.5 * 60.1 ± 2.0 *, ** Polymorphic nuclear leukocytes (%) 17.6 ± 0.3 51.6 ± 1.5 * 22.5 ± 1.8 * ** 50.3 ± 1.4 * 20.4 ± 1.9 *, ** 43.5 ± 1.3 * 20.9 ± 1.2 *, ** Mononuclear leukocytes (%) 3.1 ± 0.2 3.3 ± 0.1 3.1 ± 0.1 *, ** 5.5 ± 0.8 * 4.2 ± 0.3 *, ** 8.5 ± 1.1 * 5.8 ± 1.7 *, ** The differences in the indicators in the groups are significant at p <0.05: from the norm *, after treatment from the standard method of treatment **

When conducting a cytological study, we found that after our local treatment, the percentage of cell integrity mainly increased. Moreover, the number of epithelial cells when using hepone increased three times, and the number of polynuclear leukocytes and mononuclear cells decreased by half (table 2), similar changes in the group receiving standard therapy are less pronounced. The results obtained indicate an active relief of the inflammatory process with gepon and the effect of this drug on the induction of tissue regeneration in the oral mucosa.

In studies of the concentration of cytokines in saliva (Table 3), it was found that in patients with rash of lichen planus on the oral mucosa, it was higher than normal, however, the degree of such an increase for different mediators varied significantly. The content of TNF-α - the leading pro-inflammatory immunocytokine of the acute phase, with lichen planus increased by 6-10 times, and significantly higher with erosive-ulcerative form. The amounts of INF-γ in saliva were of varying degrees of severity higher than normal. 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.

Before treatment, in patients with lichen planus of the oral mucosa in all forms, a significant decrease in the content of the leading anti-inflammatory cytokine, IL-4, was observed. Based on the data obtained by us, it should be noted that the development of lichen planus is accompanied by significant changes in the state of the immune defense mechanisms of the oral cavity, which is revealed by analyzing the composition of the cells of the subgingival pocket, as well as the content of immunoglobulins and cytokines in saliva.

Table 3 The content of certain cytokines and immunoglobulins in saliva (g / liter) before treatment of patients with lichen planus Form indicator Healthy Typical Exudative-hyperemic Erosive and ulcerative Standard therapy Gepon Standard therapy Gepon Standard therapy Gepon INF-γ (PCG / ml) 42.44 ± 3.14 465.36 ± 4.4 * 455.16 ± 4.4 * 460.33 ± 8.55 * 462.65 ± 8.55 * 793.32 ± 122.11 * 796.32 ± 122.11 * TNF-α (PCG / ml) 122.65 ± 8.14 776.33 ± 18.76 * 779.13 ± 18.76 * 797.67 ± 26.86 * 780.17 ± 26.86 * 944.49 ± 13.34 * 945.49 ± 13.32 * IgA 0.13 ± 0.05 0.22 ± 0.05 * 0.22 ± 0.08 * 0.23 ± 0.07 0.24 ± 0.08 * 0.29 ± 0.09 0.28 ± 0.09 * sIgA 0.50 ± 0.05 0.64 ± 0.10 * 0.62 ± 0.10 * 0.66 ± 0.10 * 0.69 ± 0.10 * 0.72 ± 0.10 * 0.74 ± 0.10 * IgG 0.09 ± 0.02 0.25 ± 0.10 * 0.21 ± 0.10 * 0.31 ± 0.10 * 0.31 ± 0.10 * 0.33 ± 0.24 0.33 ± 0.24 * IL-4 (PCG / ml) 12.56 ± 3.25 08.46 ± 1.78 * 09.16 ± 1.9 * 07.73 ± 3.2 * 07.89 ± 3.4 * 07.3464 ± 7.78 * 07.34 ± 6.77 * The differences in the indicators in the groups are significant at p <0.05: from the norm *, before treatment from the standard method of treatment **

In all patients, lichen planus after traditional treatment in saliva showed a tendency to a decrease in IgG class immunoglobulins; IgA, a sIgA, and after treatment with gepon their content in saliva at all degrees of severity significantly decreased (table 4).

Table 4 The content of certain cytokines and immunoglobulins in saliva (g / liter) after treatment of patients with lichen planus Form indicator Healthy Typical Exudative-hyperemic Erosive and ulcerative Standard therapy Gepon Standard therapy Gepon Standard therapy Gepon INF-γ (PCG / ml) 42.44 ± 3.14 112.64 ± 13.66 * 42.76 ± 10.66 *, ** 143.37 ± 12.64 * 58.62 ± 10.14 *, ** 152.11 ± 7.2 * 59.10 ± 7.4 *, ** TNF-α (PCG / ml) 122.65 ± 8.14 217.58 ± 18.62 * 169.56 ± 11.62 *, ** 225.44 ± 38.24 * 175.44 ± 18.21 *, ** 267.30 ± 4.18 ** 183.30 ± 24.18 *, ** IgA 0.13 ± 0.05 0.18 ± 0.08 * 0.15 ± 0.06 *, ** 0.22 ± 0.08 * 0.18 ± 0.05 *, ** 0.22 ± 0.05 0.18 ± 0.02 *, ** sIgA 0.50 ± 0.05 0.56 ± 0.14 * 0.50 ± 0.23 *, ** 0.58 ± 0.12 * 0.52 ± 0.12 *, ** 0.59 ± 0.05 * 0.53 ± 0.26 *, ** IgG 0.09 ± 0.02 0.24 ± 0.07 * 0.14 ± 0.11 *, ** 0.32 ± 0.14 * 0.18 ± 0.05 *, ** 0.35 ± 0.02 * 0.29 ± 0.02 *, ** IL-4 (PCG / ml) 12.56 ± 3.25 33.49 ± 28.64 * 42.49 ± 18.62 *, ** 47.81 ± 12.17 * 48.67 ± 4.77 *, ** 55.89 ± 8.61 * 58.89 ± 18.65 *, ** The differences in the indicators in the groups are significant at p <0.05: from the norm *, after treatment from the standard method of treatment **

As a result of the therapy, a decrease in the content of TNF-α was noted in the saliva of patients, a significant increase in the content of the anti-inflammatory cytokine - IL-4. The use of gepon in the treatment of lichen planus of the oral mucosa is accompanied by normalization of the composition of the cells of the periodontal pocket: the predominance of epithelial cells over white blood cells, a decrease in the number of destroyed cells. During treatment, a tendency towards normalization of the content of immunoglobulins was recorded.

Thus, the combined use of this immunomodulator in various forms of lichen planus of the oral mucosa has a corrective effect on local immunity and provides greater clinical efficacy of therapy than standard therapy.

These changes manifest themselves to varying degrees depending on the form of the mucous membrane pathology and reflect inflammation processes in the lesion focus and activation of immune defense mechanisms (an increase in the cellular composition of polymorphonuclear and mononuclear leukocytes that migrated to the lesion, an increase in the content of proinflammatory cytokines (TNF-α and IL-1 β), an increase in the concentration of IgG and IgA immunoglobulins and cytokines in saliva.

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 mouth, which acquired the usual color and appearance; exudation, swelling, stagnant-hyperemic background leveled. The process of transformation of clinical forms into less severe ones was observed.

Having received a positive dynamics of the course of all forms of lichen planus of the oral mucosa with the use of gepon, we have developed an effective treatment regimen for the disease using this immunomodulator.

Case Study

Patient N., 48 years old, medical history No. 718, was admitted to inpatient treatment with OKVD in Kursk on 10.04.2009 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.

Laboratory values:

1. Cell nuclei (%) - 17

2. Destroyed cells (%) - 29

3. Epithelial cells (%) - 17

4. Polymorphic nuclear leukocytes (%) - 76

5. Mononuclear leukocytes (%) - 17

6. INF-γ (pkg / ml) - 790

7. TNF-α (PCG / ml) - 950

8. IgA - 0.27

9. sIgA - 0.72

10. IgG - 0.34

11. IL-4 (PCG / ml) - 07.35

Against the background of traditional therapy, the patient received the hepone preparation (Immafarma LLC) by irrigation of the mucous membranes of the oral cavity with a 0.04% hepone solution, followed by the application of gauze napkins moistened with a 0.04% hepone solution for 30 minutes on the inflamed areas of the skin. Before using the drug, the mucous membrane was irrigated with saline. The procedures were performed 1 time per day, for a course of 10 procedures.

The values of laboratory parameters after therapy:

1. Cell nuclei (%) - 8

2. Destroyed cells (%) - 8

3. Epithelial cells (%) - 60

4. Polymorphic nuclear leukocytes (%) - 21

5. Mononuclear leukocytes (%) - 5

6. INF-γ (pkg / ml) - 59

7. TNF-α (pkg / ml) - 184

8. IgA - 0.17

9. sIgA - 0.53

10. IgG - 0.22

11. IL-4 (PCG / ml) - 52.3

On the 15th day of treatment, the oral mucosa acquired the usual color and appearance; exudation and swelling have completely disappeared.

Thus, the task has been achieved due to local application of the immunocorrecting drug hepon.

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

1. Achieving high efficiency in the treatment of manifestations in the oral mucosa with lichen planus in a short time.

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

Claims (1)

A method of treating lichen planus of the oral mucosa, comprising topical application of a drug to the oral mucosa, characterized in that the patient is irrigated with a 0.04% hepone solution, followed by application of gauze napkins moistened with the same solution to 30 min once a day for ten days.