XIV Международная студенческая научная конференция Студенческий научный форум - 2022

Rosacea is a chronic inflammatory disease that affects 10% of the population. The prevalence of rosacea is highest among light-skinned people, especially those of Celtic and Northern European origin [1, р. 273; 2, р. 66]. Rosacea is a major medical and social health problem. The clinical picture of the disease is observed both at the age of 13-19 and in the range of 30-40 years, when the onset of the disease is most likely, mainly in persons with the first or second skin phototype [3, р. 1124]. Rosacea is a multifactorial, polyethological disease with a certain genetic predisposition. Often, unfavorable factors include dry skin, which is a favorable environment for the addition of fungal and bacterial flora. Dry skin is accompanied by hypersensitivity and increased irritability under the influence of exogenous factors [4, р. 41]. Rosacea has a serious psychosocial impact on the patient's life [5, р. 719]. Such unfavorable factors as environmental pollution, smoking, excessive insolation lead to frequent recurrence. Sun-damaged skin includes all the changes associated with insolation (clinical, histological and functional) [6, р. 75]. It is known that inflammation plays an important role in the formation of lesions [7]. Vascular disorders, gastrointestinal pathology, endocrine system dysfunctions, psychosomatic and immune disorders, as well as endocrine factors play a leading role in the pathogenesis of rosacea [8, р. 115]. The pathogenesis includes a complex interaction between a violation of the regulation of innate immunity, a violation of the regulation of the vascular nervous system and excessive growth of commensal organisms such as Demodex folliculorum (D. folliculorum) and Staphylococcus epidermidis [9, р. 26]. It can often be complicated by a secondary infection. Pyoderma is one of the most common infectious dermatoses with a frequency of occurrence in the general structure of skin diseases [10, р. 19]. Alimentary factors such as hot drinks, various spices contribute to the stimulation of the mucous membrane of the gastrointestinal tract causing the expansion of blood vessels in the face. J. Wilkin et al. it was found that hot water with a temperature of more than 60 ° C contributes to blood flushes to the face, not caffeine itself, but hot water with a temperature of more than 60 ° C [11, р. 468]. Common forms can lead to a more severe course, up to generalized inflammation of the skin. Erythroderma can be severe with fever, severe malaise [12, р. 6]. Gupta M. et al. it was found that the formation of rosacea is not affected by alcohol-containing products. The most frequent provoking trigger factors that contribute to the appearance of a clinical picture at the beginning of the disease and contribute to the aggravation of the skin process may be tobacco products, skin photosensitivity, family predisposition to rosacea [13, р. 1176]. One of the most frequent provoking causes of rosacea is the detection of ticks of the genus D. folliculorum. The clinical picture of rosacea creates a favorable ground for the existence of D. folliculorum, increasing its density of skin colonization and contributing to increased itching, burning, etc. For the treatment of specific clinical manifestations observed in various subtypes of rosacea, various physical methods, local and systemic remedies are available, including oral isotretinoin, which has been recognized as valuable for intractable cases of rosacea [3, р. 1124; 14, р. 54]. The response to therapy of rosacea patients plays a crucial role in determining the duration of treatment [15, р. 506].

Purpose of the study.

To study the efficacy of small doses of isotretinoin in patients with papulopustular rosacea.

Materials and research methods.

23 patients with papulopustular rosacea (PPR) of moderate severity were under observation. Rosacea was diagnosed clinically with the observation of erythema (transient redness or persistent) and/or papules, pustules and telangiectasias concentrated on convex areas of the face without involvement of the periocular skin. PPR were examined for the presence of secondary signs of rosacea (clinical symptoms, edema, eye damage, peripheral localization, physiological changes, etc.). The severity of rosacea was assessed for each trait (erythema, peeling, papules and pustules) from 0 for absence to 3 for the most severe. All patients were divided into two groups. In the first group, PPD received isotretinoin at a dose of 0.1 mg / kg, in the second group – 0.3 mg / kg of body weight. The course of treatment was 4.5 months. The exclusion criteria were PPD during pregnancy and lactation. To assess the clinical efficacy of therapy at the final stage, the following criteria were used: complete disappearance of papulopustules, excellent: reduction of papulopustules by 75-99%, good: decrease by 50-74%, controlled: decrease by 25-49% and no response. The secondary results of evaluating the clinical efficacy of therapy were overall patient satisfaction and isotretinoin tolerability. Undesirable drug reactions were determined by their severity: serious, frivolous and severity: mild, moderate, severe. Pregnancy testing was also carried out, Demodex folliculorum (D. folliculorum) was determined in the laboratory. The study used the Dermatological Quality of Life Index (DLQI), which is a compact health-related quality of life index containing ten questions. DLQI depends on the opinion of patients about themselves over the past week. DLQI includes aspects of life such as symptoms, feelings, leisure, work and study, personal relationships, daily activities, received treatment. There were four possible answers to all the questions. The results of the DLQI responses received were recorded from 0 to 30 and were recorded before and after treatment with PPD. The influence of clinical and demographic factors was carried out using the Student's t-criteria. Statistical research methods were carried out using a package for Windows

Research results and discussion.

To fulfill the tasks set in the work, 23 patients with papulopustular rosacea treated with isotretinoin were examined. The average age was 47 years (range 19-75 years). Among the examined patients, 8 (34.7%) patients had adult acne visualized, two had concomitant seborrheic dermatitis. The average overall DLQI score at the initial examination was 7.19±5.21 (range from 0 to 24). The overall DLQI scores at the initial examination significantly depended on age, gender, age of onset of the disease, subjective symptoms (especially itching, burning sensation, sensitive skin, burning sensation, cosmetic intolerance and pain), provoking factors (stress, sunlight, hot air, wind, spicy food, chemical irritations, cosmetics, beverages with a temperature of more than 60 degrees, the use of topical corticosteroids), previous treatment methods (topical agents with metronidazole, antibiotics, steroids, systemic tetracyclines ), the possibility of living with rosacea. Rosacea affected the quality of life of women to a greater extent than men (p<0.001). During the initial examination, DLQI did not significantly affect the education of patients, marital status, social status of patients living alone, profession (indoors, outdoors), duration of the disease, duration of existing symptoms, history of acne, erythema, skin phototype, medical history in the past, history of medication or vitamins, menopause, duration of menopause, family history of rosacea, social support, certain symptoms of patients (photosensitivity, seborrhea, thickening of the skin, discomfort with water), certain provoking factors (hot bath, cold air, exercise, alcohol, menstruation), clinical types, localization of rosacea, the presence of eye involvement, phyma, seasonal changes (p>0.05).

The analysis of the results of the clinical examination of PPD was carried out in both groups before and after treatment.

As a result of the study, it was found that the overall DLQI score significantly influenced patients, gender, drug choice, the development of side effects from medications, housing conditions and the possibility of living with rosacea. In the second group, there was a decrease in the average overall DLQI score by 39% compared to the average DLQI scores before treatment, while in the first group only by 23%. It was shown that the overall DLQI score did not significantly affect the age of patients, the presence of social support, seasonal changes, patients with socio-economic status, clinical types of rosacea foci, the presence of fima (p>0.05).

Both after treatment with isotretinoin at a dose of 0.1 mg/kg and at a dose of 0.3 mg/kg, overall patient satisfaction with the results of treatment was observed. One patient (4.3%) stopped taking isotretinoin due to side effects. A total of 22 patients were treated at the end of the study period.

Of the 22 patients with long-term follow-up, rosacea passed in 68.2%, was considered excellent in 18.2% (four patients) and was controlled in 1% (one patient).

Complete disappearance of papulopustules after therapy of patients with PPD in the first group was observed in 27.3% of cases. Isotretinoin at a dose of 0.3 mg/kg contributed to the complete disappearance of papulopustules in 40.9% of cases. Both in the first and in the second group, a decrease in papulopustules by 75-99% was recorded in 9.1% of PPD. A decrease of 50-74% was observed in 9.1% of patients in the first group, no such patients were observed in the second group. Controlled reduction of papulopustules by 25-49% was also recorded only in the first group and amounted to 4.5% of cases.

No serious side effects were noted. Ten patients (45.5%) reported no side effects at all. The most common side effect was cheilitis in 54.5% of patients, which was considered mild and treatable in all but one patient.

Four patients had additional moderate rosacea of the eyes. Three (75%) of them had significantly improved eye symptoms.

At the end of the study period, it was found that isotretinoin is highly effective in the treatment of refractory rosacea foci.

According to the results of the study, it was revealed that meteorological weather conditions (heat, wind), increased temperature of food and drink, physical activity, beverages containing alcohol, spicy seasonings, cosmetics and medicines were unfavorable factors in PPR. A significant role in pustular and ocular rosacea was assigned to Staphylococcus epidermidis. It is known that a number of bacteria react differently even at slightly elevated temperatures. In long-term PPR sufferers, gram-negative microorganisms indicate the severity of the disease and the result of inadequate treatment with antibacterial agents.

It is known that bacterial antigens of Bacillus oleronius isolated from D. folliculorum ticks lead to stimulation of the immune response in PPD. According to the results of the study, the most frequent localization of D. folliculorum in PPD was the nasal area (36.3%), in second place was the forehead area (27.2%), in third place was the perioral area (22.7%). The next recorded localizations were cheeks (18.2%) and periorbital (13.6%). D. folliculorum was observed less frequently in the chin area (9.1%) and neck (4.5%) in PPD. Density D. folliculorum affects both the clinical manifestations of the disease and the severity of the inflammatory response in response to the presence of a tick. Already formed rosacea is a favorable environment for the existence of D. folliculorum and predisposes to the progression of the clinical picture of both objective and subjective symptoms.

As a result of the study, the manifestations of diseases of the digestive system were observed in 56.5% of PPR. The relationship between diseases of the digestive system and rosacea is associated with the hyperproduction of vasodilation mediators. Many researchers identify Helicobacter pylori (H. pylori) bacteria in the gastrointestinal tract and associate a large number of them with the severity of the clinical picture of rosacea [4, р. 41]. H. pylori contribute to the formation of vasoactive peptides, release toxins that predispose to the state of hot flashes. Gastrinemia may be registered in PPR with H. Pylori.

In the conducted study, 31.8% of PPD associated the manifestations of the clinical picture with disorders of the endocrine system. A decrease in lipase secretion and diabetes mellitus contributed to metabolic disorders in PPR. Disorders of the endocrine system can contribute to recurrent papulopustular rosacea.

Systematic emotional stress both in the family and at work was found in 40.9% of PPD. At the same time, only a high degree of nervousness, anxiety-depressive reactions affecting mental health cannot be only a consequence of the appearance of patients.

Vascular disorders in the facial area were associated with greater sensitivity of bradykinin receptors, which confirm the importance of provoking pathogenetic factors of rosacea formation. The localization of hot flashes in the face area is facilitated by kallikrein, produced by the salivary glands. Catecholamines are also produced by the gastric mucosa under the influence of alcohol-containing products and stress factors. Kallikrein contributes to the increased formation of bradykinin, which has a vasoactive effect.

According to the results of the study, it can be argued that isotretinoin can improve the condition of rosacea. It is known that various physico-chemical triggers, such as heat, ultraviolet light or spices, cause neurogenic reactions that lead to vasodilation and symptoms of sensitive skin. This, in turn, regulates the innate immune system through a Toll-like type 2 receptor, which triggers the release of kallikrein 5 from epidermal keratinocytes. This enzyme is responsible for activating the antimicrobial peptide cathelicidin in its pro-inflammatory form, which further aggravates skin inflammation and vasodilation. Isotretinoin reduces the size of the sebaceous glands by reducing the proliferation of basal sebocytes, suppresses sebum production and prohibits the differentiation of sebocytes. It is known that isotretinoin in low doses causes a shift in lipid fractions from the norm: triglycerides predominate, followed by squalenes and free fatty acids, which can normalize an exaggerated innate immune response mediated by a Toll-like type 2 receptor. In addition, isotretinoin alters the microbiome of the skin, in particular, Propionibacterium acnes and Malassezia spp. According to our study, we can assume that isotretinoin indirectly affects the population of Demodex folliculorum. Isotretinoin can also improve erythema and rosacea redness due to its antiangiogenic effects.

Thus, rosacea is a chronic inflammatory skin disease that requires long-term therapy. The study showed that low doses of isotretinoin are a good alternative for PPR, which confirms the significant role of isotretinoin in the pathogenetic process in these patients.

Conclusions

1. It was found that in the group of patients with papulopustular rosacea treated with isotretinoin at a dose of 0.3 mg /kg, the complete disappearance of papulopustules after therapy (40.9%) occurred 1.5 times faster than in the group treated with isotretinoin at a dose of 0.1 mg/ kg (27.3%). In patients with papulopustular rosacea, Demodex folliculorum (36.3%) was more common in the nasal region.

2. The most common and easily treatable side effect was registered cheilitis (54.5%). No serious adverse drug reactions were detected.

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