[PATHOGENETIC FEATURES AND METHODS FOR TREATMENT OF VARIOUS FORMS OF ROSACEA].

The aim of the work was to study the features of the pathogenesis of various clinical forms of rosacea (the presence of mite Demodex folliculorum, the determination of VEGF, IL-2 IL-6, IL-8) and, based on the obtained results, to ensure adequate methods of therapy. Mite identification was performed by microscopy. The concentration of cytokines in patients with various clinical forms of rosacea (papulopustular form 15 patients, steroid form - 15, erythematous telangiectic form - 10, Ophthalmo Rosacea - 3, rhinophyma - 3) was determined by enzyme immunoassay using appropriate monoclonal antibodies and expressed in samples. Based on the results we obtained in the local treatment of patients with papulopustular rosacea (with a high population density of demodicosis ticks and an increased concentration of IL-8 in the blood), 1% ivermectin cream was applied externally to the skin of the face 1 time per day every day for the entire course of treatment (3-4 months). In patients with erythematous-teloangiectatic form (with a high cytokine VEGF, IL-8), a combined phased use of 1% pimecrolimus cream 14 days and 0.5% bromonidine tartrate gel was administered once a day - 14 days (with a single course of 1 month). In patients with a steroid form of rosacea with a high concentration of cytokines (IL-2, IL-6, IL-8), 1% pimecrolimus was administered 2 times a day - 1 month, 1% ivermectin 1 time a day - 14 days. During therapy, patients with advanced treatment were divided into 2 groups. Patients of group 1, who received externally 1% ivermectin 1 time per day as the main therapy, in the evening for 16 weeks. Group 2 applied 1% ivermectin and 1% pimercolimus cream for 16 weeks. In group 2 patients showed a significant improvement in a shorter time (4 weeks compared to 8 weeks in 1 group of patients). Taking into account the torpid flow and the difficulty of rosacea therapy, the pathogenetic approach when choosing new external preparations, opens promising directions for further deeper study of the pathophysiological mechanisms underlying the individual clinical forms of dermatosis. At the same time, the efficacy and safety of using ivermectin, pimecrolimus, and brimonidine tartrate in the treatment of various forms of this dermatosis suggests their widespread use in practical dermatology.

[FEATURES OF ROSACEA PATHOGENESIS IN PERIMENOPAUSAL WOMEN].

In patients with rosacea, the monitoring of blood melatonin in the menopausal period, as one of the criteria for assessing the severity of the disease, seems appropriate and pathogenetically justified. The aim of this study was determination of blood melatonin, VEGF, IL-8 concentration in perimenopausal period of women suffering by rosacea. 43 to 65 years old 15 women with various clinical manifestations of rosacea, and severe climacteric syndrome were under observation. The control group consisted of 15 female patients with rosacea but without climacteric syndrome. Melatonin, VEGF,IL-8 level in serum were determined by ELISA (IBL - international - reagent), the results were expressed in pg/ml).As the results of the study showed, the concentration of vasoactive peptides in patients with rosacea differes significantly from those in the control group. Increase the concentration of cytokinesin in the blood of patients with rosacea indicate that they are playing significant role in the pathogenesis of rosaceaAccording to the results of the study, the concentration of melatonin was reduced in all patients with rosacea (the main group). The degree of reduction was in direct correlation with the severity of climacteric syndrome (11,6÷1,5 pg/ml at a rate of ≥ 20,0 pg/ml). In the control group, the melatonin concentration was approaching to the norm (19.1 pg/ml). Statistical analysis of received data revealed the correlation in between of the severity of dermatosis and changes in lipid metabolism and concentration of melatonin (R = 0,91; p <0,05) in the main group of patients (with rosacea and climacteric period). Thus, on the basis of the obtained results it can be concluded that the inclusion of melatonin-containing preparations in prescription for rosacea patients having climacteric syndrome pathogenetically is justified.

[THE ROLE OF SOME VAZOACTIVE PEPTIDES IN THE PATHOGENESIS OF EARLY FORMES OF ROSACEA AND THE HEMOSTASIS SYSTEM].

Recently, the role of vasoactive peptides has been increasingly discussed in the pathogenesis of rosacea. The most attention is paid to the growth factor of the vascular endothelium (VEGF). VEGF affects angiogenesis and survival of immature blood vessels. Cytokine contributes to an increase in the level of IL-8, which plays a role in the development of inflammation. VEGF is synthesized by activated keratinocytes as a result of various factors. In particular, after exposure to ultraviolet irradiation, the production of cytokines-IL-1 and TNF-α-is provoced, which stimulate keratinocytes to synthesize of VEGF. The latest data on the state of the coagulation system in rosacea patients indicate a shift in the functional activity of the hemostasis system toward hypercoagulability. The aim of the study was to study the relationship between changes in the concentration of certain vasoactive peptides and the parameters of the hemostasis system in patients with rosacea. The state of the hemostasis system was assessed by prothrombin and thrombin time. The content of fibrinogen, fibrinolytic activity of blood, and also prothrombin index were determined as well. The concentration of free VEGF, IL-8 in the serum was determined by the method of enzyme immunoassay In the study, patients with rosacea, according to their age, were divided into 2 groups: -I group - patients aged 35 to 45 years, II group - patients aged 45 to 65 years. As the results of the study showed, the concentration of vasoactive peptides in patients with various clinical forms of rosacea differs significantly from those in the control group. In patients with various clinical forms of rosacea, the tendency of changes in all parameters (thrombin time, prothrombin time, fibrinogen, prothrombinic index) of the state of the coagulating system of blood with the manifestation of hypercoagulability is traced. And if the change in the content of cytokines was observed equally often in all observed patients, the manifestations of hypercoagulability were most pronounced in the second group of patients (aged 45 to 65 years) Thus, the results of the study allow us to conclude that an increase in the concentration of cytokines (which are a potent provoker of changes in permeability, atony and brittleness of the vessel walls), as well as hypercoagulable phenomena, indicative of ongoing microcracking processes, are the leading links in the pathogenesis of early forms of rosacea.

[RISK-FSCTORS OF CARDIOVASCULAR DISEASE IN PATIENTS WITH ROSACEA].

The purpose of the research was to study the lipid profile, some indices of hemostasis and cytokine status of rosacea patients with severe climacteric syndrome. Serum lipid profile was studied by means of the following parameters: total cholesterol, high density lipoproteins (HDL), low density lipoproteins (LDL), triglycerides (the study of lipid profile was performed by the device "INTEGRAM +400" (Company "ROSH¼). Haemostatic system was evaluated in terms of prothrombin, thrombin time. Content of fibrinogen, fibrinolytic activity, and prothrombin index were determined. The concentration of free VEGF (vascular endothelial growth factor) and IL-8 were measured by ELISA. The results of these studies suggest that the phenomenon of hyper coagulation and disorders in lipid profile of blood serum in patients with rosacea with climacteric syndrome can be considered as risk factors of cardiovascular disease. From the other side, as a powerful provocateur of increased permeability, atony and fragility of vessel walls, VEGF, IL-2, IL-8 may be directly related to the mechanism of the development of cardiovascular disease in rosacea patients.

[EFFICACY OF COMBINED USE OF ANTIOXIDATIVE AND PHOTOTHERAPY IN THE TREATMENT OF VITILIGO].

Despite of numerous investigations, carried out practically in all countries of the world for the study of vitiligo and the search for its new effective therapies, pathogenic mechanisms of vitiligo are still poorly understood, and the proposed treatments are not perfect. One of the most accepted theories of the pathogenesis of vitiligo is an oxidative stress theory, according to which a series of biochemical anomalies cause oxidative stress, leading to accumulation of melanocytotoxic substances and inhibition of natural processes of detoxification with subsequent destruction of melanocytes in vitiligo focus. On the other hand, the use of antioxidants in combination with ultraviolet therapy of dermatological diseases, has been theoretically proved by biophysical studies, according to which- the antioxidants inhibit the oxidation of products, formed in the skin after ultraviolet irradiation and greatly reduce erythema sensitivity (1.5-2 times). Due to this effect, the power of radiation exposure can be approximately increased many times. Based on the foregoing, the use of antioxidants during phototherapy of vitiligo pathogenetically is justified. The aim of the study was to evaluate the therapeutic efficacy of Se ACE in treatment of patients with various forms of vitiligo. 35 patients (23 women and 12 men) aged 18 to 40 years with duration of the pathological process from 2 months to 15 years were under observation. 17 of these were diagnosed with a form of non segmental vitiligo (NSV), 18- segmental vitiligo. In 11 patients onset of the disease was not connected with any other problem, 24 noted the appearance of white spots after stress. Vitiligo patients were divided into 2 groups: the study group and the group of comparison. The study group included 17 patients (9 women and 8 men) aged 18 to 40 years with duration of the disease from 2 months to 5 years. The comparison group consisted of 18 patients (10 women and 8 men). Distribution of patients in both groups was homologous by the sex, age, duration and clinical forms of dermatosis. All patients underwent phototherapy. In the study group Selenium was used as an antioxidant, which was administered at a dose of 1 capsule 2 times a day for a month. Phototherapy was performed by means of MEDlight OCTAderm (3 times per week, the course of treatment - 15 procedures). After a course of phototherapy in combination with Selenium (study group), 1 patient had complete regimentation, in 43.5%of patients with NSV whisk of regimentation was formed, in 60.9% of patients with partial NSV we observeda partial regimentation in the form of pigmented inclusions withinthe foci of depigmentation. In the group of comparison we did not reveal any case of full regimentation, the whisk of hyperpigmentation was observed only in 34.7%, formation of pigmented inclusions within the foci of depigmentationwere revealed in 29.1% of cases. Thus, the phototherapy of vitiligoin combination with Selenium gives a well pronounced therapeutic effect, the clinical picture of which can be described as the following: high frequency, fast enough occurrence (2-3 months), cosmetic favorability-regimentation has uniform character without noticeable hyperkeratosis and peeling, as well as without any redness and hyperpigmentation.

[Capillary fragility and some hemostatic parameters in patients with rosacea].

The aim of the study was to investigate the association between capillary fragility and some hemostatic parameters, lipid profile in patients with rosacea. 50 patients (30 women and 20 men) aged 35 to 65 years were under observation. Control group consisted of 50 healthy persons, adequate to comparison group by sex and age. To determine the resistance of the capillary, Rumpel-Leede cuff (tourniquet test) was used which consists in determining the formation of petechial hemorrhages on the skin in the area of ​​short-term increase in venous pressure. The hemostatic system was evaluated in terms of prothrombin and thrombin time. Content of fibrinogen and fibrinolytic activity of blood were determined also. The serum lipid profile was studied by means of the following parameters: total cholesterol, triglycerides, HDL (high density lipoprotein), LDL (low density lipoproteins). The survey revealed that in 25 patients the arm cuff test was positive, whereas in the control group, only 2 cases it was weakly positive. Manifestations of hypercoagulation were found in half of patients with a positive cuff test, almost in half of the patients an increased level of fibrinogen and the reduced fibrinolytic activity in blood serum has been revealed. Significant correlation with lipid metabolism have not been identified. Phenomenon of hypercoagulation in rosacea patients on the one hand suggests the existence of processes of microcoagulation, on the other hand the connection with the results of a cuff test can be used to predict the severity of the dermatosis and the possible risk for developing of cardiovascular disease.

[Peculiarities of cytokine status in patients with vitiligo and stress in anamnesis].

The aim of our study was to investigate the content of some proinflammatory cytokines (IL-2, IL-6) in the serum of patients with vitiligo and stress in anamnesis. Cytokine levels in serum were measured in 50 patients with vitiligo (20 men and 30 women aged from 18 to 65 years old.) All the patients were divided according to anamnesis (27 patients with stress in anamnesis and 23 patients, where the onset of the disease was not preceded by stress). Patients of both groups were similar in terms of shape (according to T. Fitzpatrick classification) and in terms of the dermatosis stages. Concomitant autoimmune or inflammatory diseases of the skin in our vitiligo patients were not observed. The cytokines in the blood serum of vitiligo patients were determined by ELISA using the corresponding monoclonal antibodies. Student's t-test was used for evaluation of statistical significance of received results (p < 0.05 was considered as a statistically significant). Content of IL-2 in the serum of patients with vitiligo, in which stress was not preceded dermatosis, was significantly higher than that in healthy individuals (25,5 ± 7,6 vs 10,5 ± 3,6 pg/ml, p < 0,05). But the same parameter in patients with stress in anamnesis was significantly lower than those in healthy individuals (3,5 ± 1,5 vs 10,5 ± 3,6 pg/l, p < 0.05). Changes in the content of IL-6 in the serum of vitiligo patients was a similar to changes in IL-2 content, and the most significant this indicator was in patients with generalized and progressive stage of the disease. Data on increased concentrations of IL-6 agree with the majority of studies conducted earlier. For a complete analysis of our results on the reduction of the cytokines (IL-2, IL-6) content in patients with a stress in anamnesis, that will allow to identify the most effective ways to treat patients with this pathology (including their cytokine status), further research is necessary.

[Angioprotectors in the treatment of rosacea].

Rosacea - a common chronic inflammatory dermatosis (3-10% of all dermatoses) primarily affecting the skin of face. Numerous methods for the treatment of rosacea are defined by the diversity of etiologic and pathogenic factors of dermatosis, its stage and clinical form. But a significant role in its development, most researchers relate to vascular disturbances. It is suggested that vascular changes in this disease are the product of two interrelated pathological processes: the disturbances in integrity and tone of the vascular wall and disorganization of perivascular connective tissue. The results of these processes are formation of a stable dilatation of skin blood vessels clinically manifested by erythema and telangiectasia. Based on foregoing, The aim of this study was evaluation of therapeutic efficacy of Rutin Forte in complex treatment and prevention of rosacea. 30 patients with an erythematous stage of rosacea were under observation (20 women and 10 men) aged 25 to 50 years. The first group (15 patients) was treated by the standard procedure (Antibiotics, systemic metronidazole, antihistamines, traditional external therapy). Patients of the second group (15 people) additionally received a Rutin Forte containing long-acting vitamin C, zinc and selenium. The drug was administered at a dose of 2 capsule per day. Duration of treatment - 2 to 3 months. Observation period after treatment were 12 months. During this period we revealed a significant reduction of erythema, recurrence of disease in the second group of patients was not observed, but in the group of comparison recurrences were detected on 3rd month of follow up and the degree of erythema reduction was significantly less. Thus, the study revealed that Rutin Forte is an effective means for the treatment and prevention of the torpid relapsing forms of rosacea on erythematous stage of dermatosis.