RU2620683C1 - Method for treatment of patients with sclerotic vulvar lichen - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method involves application of a complex therapy with the diagnosed sclerotic lichen, using autologous cellular regeneration by autoplasma enriched with platelets in combination with an antiviral drug and low-intensity laser light (LILI).

EFFECT: use of the invention allows to reduce itching and dystrophic processes in the vulva area, accompanied by inflammatory manifestations in the dermis, fragmentation and disintegration of the elastic and nerve fibers, microcirculatory disturbances that characterize the sclerotic lichen, with formation of remission and prevention of disease progression into oncopathology.

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Description

The invention relates to medicine, namely to the treatment of patients with sclerotic lichen.

The main features of sclerotic lichen are marked painful, sometimes unbearable itching and vulvar atrophy, inability to have sex, frequent and painful urination, urinary incontinence - leading to the emergence of neuropsychiatric disorders, violation of social relationships, significantly reducing the quality of life of women (1, 2, 3 ) In the initial stage of the process, hyper-parakeratosis of the follicular holes and minor lymphocytic infiltrate are noted. The epidermis with a slight change in the interventricular processes. The basement membrane is locally minimally thickened. At the same time, microcirculation disorders, accumulation of small cell infiltrate, leading to tissue hypoxia, are recorded in the tissues. In the dermis, lymphocytic, sometimes plasma cell infiltration is noted. In dermal infiltrate, T cells predominate with respect to B cells. Sometimes a monoclonal increased radius of action of the T-cell receptor gamma chain gene is found in the lymphoid infiltrate. The accumulation of tenascin, fibronectin and fibrinogen or inflammatory fibrinogen cytokines (such as interleukin 4, 6, tumor necrosis factor and gamma interferon) can lead to fibrosis, which, in turn, along with the homogenization of the papillary dermis along with the destruction and loss of melanocytes, reduced transport of melanosomes to basal keratinocytes, as well as reduced production of melanin lead to fairly typical depigmentation. With a progressive process, increased hyperkeratosis is noted, edema occurs in the basal layer of the epidermis, dermal sclerosis, hyperkeratosis and atrophy of the epidermis, its disorganization, separation of cells from the basement membrane. Edema of the dermis is accompanied by homogenization of collagen fibers, as well as fragmentation and decay of elastic fibers under the influence of increased elastase activity. Fragments are also exposed to nerve fibers. Increased homogenization of perivascular connective tissue leads to obliteration of arterioles and further exacerbates blood circulation in the vulva. These changes are due to the influence of neuro-endocrine-metabolic, infectious factors. Viruses have also been studied as possible causes of the development of the disease. In patients with sclerotic deprivation of the vulva, human papilloma viruses of the highest carcinogenic type are most often distinguished (5).

Despite the wide range of conservative treatment options used: clobetasol 0.05%, hydrocortisone 1-2.5%, local agents containing estrogens, progesterone, testosterone, their effectiveness remains relatively low, reducing the painful symptom - itching of the external genital organs, does not provide complete elimination of local morphological manifestations of the disease, do not give a long remission, require long periods of treatment. Compared to traditional methods, laser therapy of sclerotic lichen is more effective, but it does not provide a guaranteed cessation of the progression of the atrophy process in the vulva (7, 8).

The method of laser therapy (8) is taken as a prototype.

Achievable during the implementation of the invention developed by us, the technical result is the achievement of a guaranteed cessation of progression of sclerotic lichen vulva, a decrease in the duration of subsequent relapses and an increase in the relapse period, and the cessation of the course of the viral infection process. Since patients with sclerotic lichen vulva most often have human papillomaviruses of a high carcinogenic type, they were studied as possible causes of the disease and the most likely cause of the oncological process.

The method is implemented as follows.

Autoplasma enriched with platelets (PRP) in a volume of 8 ml (2 vacuum tubes) using a mesotherapy technique with a 30G needle is injected into the affected area.

The next day (the exact time does not matter), a laser scanning effect on the affected area is performed, for example, using the Matrix-Urologist ALT device distantly (distance from the emitting head 1 cm) using an LO-904-20 infrared pulsed laser emitting head s ZM-50 magnetic nozzle, wavelength 904 nm, pulsed power 10-15 W, frequency 80 Hz, exposure 90-100 s, then 90-100 s a break, after which the KLO-635-15 laser emitting head illuminates the red spectrum with a continuous LLLT , wavelength 365 nm, power 15 mW for 90- 100 sec

The procedures are carried out daily, 10 sessions, before the procedure is applied a water-soluble antiviral drug with a wide spectrum of action, for example Panavir gel.

2-3 courses are carried out with an interval of 4 weeks, maintenance therapy 1 time in 6 months, which allows to stimulate the formation of collagen, induce vascular growth, provide hemostasis in the affected area, and suppress virus replication. In addition, thanks to the developed technique, laser phoresis is also carried out - enhancing the penetration of the active substance into the tissue.

A brief description of the funds that can be used.

Platelet-rich autoplasma obtained using RegenLab Swiss technology. The disposable kit for enriched autoplasma contains 2 (EXTRA) glass vacuum tubes for blood collection and processing. The tubes are equipped with a chemically inert separation membrane, which allows to maximize the separation of red blood cells and white blood cells from the platelet-rich plasma needed for the procedure. The tubes already have an anticoagulant - sodium succinate. Atraumatic blood sampling, the most gentle conditions for its processing and subsequent administration of the resulting drug contribute to the preservation of platelet integrity. Heparin, leading to premature platelet activation, is not used in the process of obtaining platelet autoplasma. Centrifugation is carried out at a speed of 3000 rpm for 5 minutes.

With the introduction of the following processes:

- the formation of a three-dimensional fibrin network;

- adhesion and activation of platelets, the release of a complex of growth factors; the involvement of macrophages and stem cells;

- increased proliferation and differentiation of stem cells, as well as proliferation of differentiated cells;

- activation of the synthesis of extracellular matrix components, including type I and type III collagen (15, 16).

The most optimal is the use of the Matrix-Urologist laser therapeutic apparatus (Registration certificate: FS 022a2005 / 2908-06). The radiation mode is pulsed and continuous. The type of laser is semiconductor. Laser emitting head LO-904-20 and KLO-635-15. Magnetic nozzle ZM-50 (mirror magnet) for magnetic laser therapy (MLT).

Mechanisms of biological effects of low-intensity laser radiation (Matrix-Urologist). The biological (therapeutic) effect of low-intensity laser radiation (coherent, monochromatic, and polarized light) can be conditionally divided into three main categories:

1. Primary effects: a change in the energy of electronic levels of living matter molecules, stereochemical rearrangement of molecules, local thermodynamic disturbances, the occurrence of waves of increased concentration of calcium ions in the cytosol.

2. Secondary effects: the propagation of waves of increased concentration of calcium ions between cells, photoreactivation, stimulation or inhibition of bioprocesses at the cellular level, a change in the functional state of both individual systems of the biological cell and the body as a whole.

3. Aftereffects: cytopathic effect, the formation of toxic tissue metabolism products, the response of immune, neurohumoral and endocrine regulation systems, etc.

The use of LILR has become widespread in various fields of medicine precisely because the few universal in nature primary photobiological reactions cause a wide variety of biochemical and physiological reactions in the body. Secondary effects are a set of adaptive and compensatory reactions that occur as a result of the implementation of primary effects in tissues, organs and the whole living organism and aimed at its restoration: activation of cell metabolism and increase their functional activity; stimulation of reparative processes; anti-inflammatory effect; activation of blood microcirculation and increased trophic support of tissues; analgesic effect; immunostimulating effect; reflexogenic effect on the functional activity of various organs and systems (9, 10).

PANAVIR ^®

Gel Active ingredient: Panavir ^® (purified extract of the shoots of the plant Solanum tuberosum) - 0.002 g per 100 g. Excipients: glycerin, polyethylene oxide 400, polyethylene oxide 4000, ethanol; sodium hydroxide, lanthanum nitrate, purified water. Antiviral agent.

It has anti-inflammatory properties on the model of experimental exudative edema. It has anti-inflammatory properties in experimental models of exudative edema, chronic proliferative inflammation.

An analgesic effect is shown on models of neurogenic pain and pain caused by the inflammatory process. It has wound healing properties in the conditions of a model of gastric ulcer. With papillomavirus infection, the drug is applied topically with a thin layer of 10 days.

Thus, the complex effect provides a synergistic effect of 3 therapeutic factors, consists in the joint unidirectional action of exogenous drugs (autoplasma platelets and antiviral gel) and endogenous stimulation of similar processes by low-intensity laser radiation.

Autoplasma platelets due to the ability to isolate growth factors from their α-granules, including platelet epidermal growth factor (PDEGF) (activation of proliferation of epidermal and epithelial cells, stimulation of angiogenesis), vascular endothelial growth factor (VEGF) (stimulation of new blood vessel growth, antiapoptosis) , fibroblastic growth factor (FGF) (stimulation of angiogenesis and proliferation of fibroblasts), helps to accelerate the growth and differentiation of healthy cells and restore damaged tissue. They are also a source of cytokines, chemokines involved in the stimulation of chemotaxis, cell proliferation. They contain dense granules that are stored and secreted after activation of ADP, ATP, calcium ions, histamine, serotonin and dopamine, elastase and lysozyme, as well as antibacterial and fungicidal proteins that can prevent infections. Platelets remain viable for 7 days and continue to generate growth factors, which allows a single injection of the drug into damaged tissue (13).

LILI enhances these effects by activating the person’s own immune system, reparative processes, has an anti-inflammatory effect, activates blood microcirculation, tissue trophism, cell metabolism and an increase in their functional activity, provides better input and bioavailability of the active substances of the drugs with anti-inflammatory, immunomodulating, regenerating antiviral actions.

The claimed sequence of techniques is extremely important to achieve the goal. First, a gel is applied, followed by laser lightning, which ensures the introduction of the active substance, as well as its bioavailability, since maximum vasodilation develops within 5 minutes after laser exposure (9, 10). The advance management of autoplasma enriched in platelets into the lesion area is due to the development time of the processes initiated by this drug, which is several hours (13).

The developed method treated 96 patients (table).

Example 1. Patient N., 29 years old, was referred by a gynecologist with complaints of severe itching in the vulva for 4 years. The history of prolonged, for 3 months, local antifungal and hormonal therapy without a pronounced effect. Visual examination noted infiltration in the clitoris, asymmetry of the labia minora, hypopigmentation in the clitoris, labia majora and perineum.

Microscopy of smears stained according to Gram in the separated urethra of the cervical canal and vagina did not contain leukocytes, the flora was not determined. In bacteriological studies, there was no growth of pathogenic and conditionally pathogenic flora. The molecular genetic method detected DNA of papillomavirus (HPV) type 16, 18 and 33, the results on other STIs and conditionally pathogenic microorganisms are negative. Vulvar biopsy: thickening of the horny and malpighian layers of the epidermis with areas of parakeratosis, scraps of elastic fibers, areas of sclerosis of collagen fibers.

Diagnosis: Sclerotic lichen vulva. Initial stage. Papillomavirus infection of the vulva.

A comprehensive treatment was carried out by the method developed by us.

During observation, a marked positive dynamics of subjective and objective manifestations of the disease was noted: itching disappeared, the tissues in the vulva became elastic, soft, moisturized. During a visual examination, a decrease or disappearance of edema in the clitoris, areas of hypopigmentation, atrophy was noted.

During control studies of the separated urogenital tract during the observation period of 6 months, HPV DNA was not determined. The use of therapy helped to improve the trophism and structure of the vulva tissue, increase local immunity and, as a result, eliminate HPV, a risk factor for the progression of the dystrophic process and its transition to oncopathology.

Example 2

Patient S., 60 years old, was referred by a gynecologist for communication with the unsuccessful therapy of sclerotic lichen. Complains of severe itching and dryness in the external genital area, discomfort during sexual intercourse. When viewed in the region of the labia minora, the vestibule of the vagina is swelling, hypopigmentation. The results of microscopic and bacteriological studies of the separated urogenital tract without pathology. The molecular genetic method using polymerase chain reaction in scrapings from the vulva revealed HPV type 16 DNA.

Diagnosis: Sclerotic lichen vulva. Initial stage. Papillomavirus infection of the vulva.

The treatment was carried out according to the method developed by us.

Against the background of therapy, itching and dryness in the external genital area disappeared. On visual inspection, the tissues in the vulva became elastic, soft, moistened. During the observation period of 6 months, the progression of the process was not noted, the patient did not show complaints, the HPV DNA was not determined.

Used sources of literature

1. Lynch P.J., Moyal-Barracco M., Scurry J., Stockdale C. Terminology and classification of vulvar dermatological disorders: an approach to clinical diagnosis // J Lower Gen Tract Dis. - 2012; 16 (4): 339-344.

2. Manukhin IB, Kondrikov NI, Kraposhina TP Diseases of the external genital organs in women. - M: MIA, 2002 .-- 303 p.

3. Kaufman R., Faro S., Brown D. Benign diseases of the vulva and vagina. - M., 2009 .-- S. 320-343.

4. Powell J.J., Wojnarowska F. Chilhood vulvar lichen sclerosus: an increasingly common problem // J Am Acad Dermatol. - 2001; 44 (5): 803-806.

5. Markina E.I. The role of infectious factors and hormonal disorders in the genesis of dystrophic diseases of the vulva and their complex treatment: Abstract. dis ... cand. honey. sciences. - M., 2003 .-- 24 p.

6. Stucker M., Grape J., Bechara F.G. et al. the outcome after cryosurgery and intralesional steroid injection in vulvar lichen sclerosus corresponds to preoperative histopathological findings // dermatology. - 2005 .-- vol. 210, No. 3. - p. 218-222.

7. Federal clinical guidelines for the management of patients with localized scleroderma. - M., 2015 .-- 20 p.

8. Broneshter D.Sh. Treatment of dystrophic processes of the vulva with the help of infrared laser radiation: Dis .... Cand. honey. sciences. - M, 1991 .-- 106 p.

9. Moskvin S.V. The effectiveness of laser therapy. - M. - Tver: LLC Triad Publishing House, 2014. - 896 p.

10. Moskvin S.V. The basics of laser therapy. - M. - Tver: LLC Triad Publishing House, 2016. - 896 p.

11. Marx R. Platelet-reach plasma (PRP): what is PRP and what is not PRP? // Implant dentistry. - 2001; 10 (4): 121-125.

12. Marx R., Carlson T., Eichstaedt R., Schimmele S., Struss J. Platelet-reach plasma: growth factor enhancement for bone grafts // Oral Surgery, Oral Medicine, Oral Pathology. - 1998; 85 (6): 6438-6446.

13. Achkasov E.E., Bezuglov E.N., Ulyanov A.A. et al. The use of platelet-rich autoplasma in clinical practice // Biomedicine. - 2013. - No. 4. - S. 46-59.

Claims (6)

A method for the treatment of patients with sclerotic lichen vulva, including the introduction of autoplasma enriched in platelets into the affected area using the mesotherapeutic technique, the next day, coverage of the lesion area first with infrared pulsed laser radiation, wavelength 904 nm, pulsed power 10-15 W, frequency 80 Hz, for 90-100 s, then, after a break of 90-100 s, continuous laser irradiation, wavelength 365 nm, power 15 mW, for 90-100 s, moreover, before laser illumination, a water-soluble antiviral preparation is applied to the area of influence, the course of treatment is 10 daily sessions, spend 2-3 courses with a break of 4 weeks.