Vol 99, No 1 (2023)

REVIEWS

Main effects of retinol palmitate on skin structures and the technology of its use in dermatological practice

Petrova S.Y., Albanova V.I., Nozdrin K.V., Guzev K.S.

Abstract

Vitamin A and its synthetic analogues are used in the treatment of numerous skin diseases. The main genomic effects of the natural form of vitamin A (retinol palmitate) are associated with its active metabolite all-trans-retinoic acid and are compensated by several restrictive mechanisms. Numerous studies have proved that retinol stimulates the proliferation of keratinocytes of the basal layer of the epidermis and endothelial cells, and also activates dermal fibroblasts to synthesize proteins of the extracellular matrix of the dermis. As a result, the thickening the epidermis, increases the mechanical strength of the skin and the hydrating ability of the dermis, angiogenesis increase. The ability of retinol to enhance the adhesion of endothelial cells and leukocytes, regulate the processes of keratinization and sebum secretion was found. Vitamin A is also a powerful antioxidant. Retinol palmitate is used as the main or auxiliary drug for the treatment of a wide range of dermatoses. The principle of application is based on clinical studies and confirmed by existing experimental data. In the treatment, the following algorithm is followed. If retinol palmitate is necessary to improve epithelialization and strengthen the epidermal barrier, medium therapeutic doses should be used. For the treatment of disorders of keratinization processes, depending on the severity of the pathological condition, medium and high therapeutic doses of the drug are used. Violation of the processes of sebum secretion and severe hyperkeratosis respond better to treatment at high therapeutic doses. It should be noted that many skins clinical manifestations mostly regress under the action of vitamin A in doses that do not lead to the appearance of signs of toxicity of the drug.
Vestnik dermatologii i venerologii. 2023;99(1):6-17
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ORIGINAL STUDIES

Influence of ABCB1 3435C>T polymorphism on methotrexate safety in patients with psoriasis

Kubanov A.A., Asoskova A.V., Zastrozhin M.S., Sozaeva Z.A., Sychev D.A.

Abstract

Background. Methotrexate is a highly effective systemic treatment for moderate to severe psoriasis, but drug toxicity may limit its use. Recent evidence suggests that it is necessary to take into account the individual characteristics of methotrexate pharmacokinetics, which are determined by the presence of polymorphisms of genes encoding methotrexate carrier proteins, to predict the risk of methotrexate-induced toxicity.

Aims. The research aim is the assessment of associations of ABCB1 rs1045642 (3435C>T) polymorphism with methotrexate safety for the patients with moderate and severe forms of psoriasis.

Materials and methods. The study included 75 patients diagnosed with psoriasis treated with methotrexate during 21 day. Data on adverse drug reactions were collected using a clinically structured questionnaire, complete and biochemical blood tests, and urinalysis. The severity of adverse drug reactions was assessed using visual analog scales and the CTCAE toxicity scale. The severity of gastrointestinal ADR was assessed using the GSRS questionnaire. Genotyping was carried out by real-time PCR.

Results. The gastrointestinal toxicity was detected in 38 patients (50.67%). The mean GSRS score was 7.97 ± 9.18. Analysis of differences in the incidence of adverse drug reactions showed the presence of statistically significant differences in the frequency of adverse drug reactions in the gastrointestinal tract: the toxic effect of methotrexate was more often observed in carriers of the T allele of the ABCB1 rs1045642 polymorphism (3435C>T), (CC — 2 (14.3%), TC — 18 (52.9%), TT — 18 (66.7%), p = 0.006). Binomial regression demonstrated the presence of a statistically significant effect of the rs1045642 SNP polymorphism of the ABCB1 gene on the incidence of ADR from the gastrointestinal tract (OR = 8.64, p = 0.008).

Conclusions. An association of ABCB1 rs1045642 SNP with the safety of gastrointestinal methotrexate therapy in patients with moderate and severe forms of psoriasis was revealed. The data obtained can be used to personalize the prescription of methotrexate to patients with psoriasis.

Vestnik dermatologii i venerologii. 2023;99(1):18-26
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To study the prevalence and clinical features of extragenital forms of sexually transmitted infections (prospective observational clinical and laboratory study)

Rakhmatulina M.R., Bolshenko N.V., Maleev V.V.

Abstract

Background. In preventing the spread of sexually transmitted infections (STIs), timely detection of extragenital localization of the pathogen is important. Modern studies demonstrate a wide prevalence of extragenital forms of STIs not only in men who practice sex with men, but also in heterosexual men and women. However, according to Russian and a number of foreign clinical guidelines, the basis of STI screening includes studies of only urethral, vaginal and cervical samples, which leads to incomplete registration of extragenital infections and contributes to their further spread.

Aims. To study the frequency of prevalence and clinical features of extragenital forms of STIs in heterosexual men and women and men who have sex with men.

Materials and methods. A prospective observational clinical and laboratory study included 57 patients with a history of unprotected orogenital and/or anogenital sexual contacts: group I (n = 20) — women practicing heterosexual sexual contacts, group II (n = 9) — men practicing heterosexual sexual contacts, group III (n = 28) — men who have sex with men (MSM). The identification of STIs was conducted by the polymerase chain reaction method and the ribosomal RNA NASBA detection method was used as an independent additional direct method.

Results. A high level of detection of STIs of extragenital localization has been established: in heterosexual women — in the rectum (10; 76.9%), in the oropharynx (9; 69.2%) and in the conjunctiva (2; 15.4%); in heterosexual men — in the rectum (2; 40%), in the conjunctiva (2; 40%) and in the oropharynx (1; 20%); in MSM — in the rectum (15; 75%), in the oropharynx (11; 55%) and in the conjunctiva (5; 25%); in 14 (36.8%) patients, STI infection of more than 2 localizations was found. In extragenital foci of chlamydia trachomatis infection in group I was most frequently detected (5; 38.5%), in group II — gonococcal infection (2; 40%), in group III — syphilis (9; 45%), gonococcal infection (8; 40%) and chlamydia trachomatis infections (8; 40%). Asymptomatic infections in conjunctiva were detected in 4 (10.5%) patients, in oropharynx — in 15 (39.5%), in rectum — in 22 (57.9%) patients.

Conclusions. The high level of detection of extragenital STIs and their frequent asymptomatic course dictates the need to study clinical samples from the oropharynx, rectum and conjunctiva not only when detecting objective and/or subjective symptoms of diseases, but also when there is a history of unprotected orogenital and/or anogenital sexual contacts, as well as when detected infections of genital localization.

Vestnik dermatologii i venerologii. 2023;99(1):27-36
pages 27-36 views

Comprehensive assessment of the dynamics of angiogenesis in patients with psoriasis treated with methotrexate

Pritulo O.A., Petrov A.A.

Abstract

Background. Evaluation of the severity of pathological angiogenesis in patients with psoriasis can be considered as a promising direction for monitoring the activity of the disease and the effectiveness of systemic therapy.

Aims. Evaluation of interconnections between indicators of angiogenesis in the skin and nail bed of psoriasis patients with clinical characteristics of disease course and therapeutic response to the use of methotrexate by a comprehensive study of the morphometric data dynamics of videodermatoscopy in vascular bed of the skin, the severity of blood flow in the dermis and nail bed during ultrasonic power dopplerography and plasma concentrations of vascular endothelial growth factor (VEGF) and endothelin-1 (En-1).

Materials and methods. Work is based on the data analysis from a survey of 82 patients with moderate to severe psoriasis vulgaris in the acute stage, who were first prescribed methotrexate in the form of subcutaneous injections at a dose of 10–15 mg per week in combination with folic acid 5 mg per week. Before treatment and three months after the start of methotrexate therapy, all patients underwent videodermatoscopy with dimension of the density and size of dilated skin capillaries, ultrasonography of psoriatic plaques and nail bed of affected nails and measurement of doppler blood flow parameters and concentration of VEGF and En-1 in blood plasma.

Results. A direct correlation was established between the average diameter of dilated skin capillaries (vascular glomeruli), the degree of increased blood flow in the doppler energy study of psoriatic plaques skin area and the plasma concentration of VEGF and En-1 and values of PASI, BSA, sPGA and DLQI indices, as well as the severity of doppler blood flow of the nail bed and NAPSI index (r = 0.21–0.73). Under the influence of methotrexate treatment, a decrease in diameter and density of vascular glomeruli (16.2 [12.9; 22.5] versus 25.2 [17.1; 33.7] µm before treatment (p = 0.002) and (44.6 [31.6; 53.3] versus 53.5 [34.6; 67.4] before treatment (p = 0.04), respectively), the degree of blood flow in area of psoriatic plaques and the concentration of VEGF and En-1 (12.5 [6.7; 26.8] pg/ml versus 19.5 [4.7; 48.1] pg/ml after treatment (p = 0.002) and En-1 (168.2 [97; 319] versus 274.5 [146; 439] pg/ml
(p = 0.003), respectively) was observed.

Conclusions. Studied indicators of angiogenesis can be used as additional criteria for assessing the degree of activity and achieving clinical improvement/remission during systemic therapy in patients with moderate and severe psoriasis.

Vestnik dermatologii i venerologii. 2023;99(1):37-47
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Periods till psoriatic arthritis onset and diagnosis in Russian patients with moderate to severe psoriasis (according to psoriasis patient registry)

Kubanov A.A., Bogdanova E.V.

Abstract

Background. Early detection of psoriatic arthritis in patients with psoriasis remains an unmet medical need. Early diagnosis and treatment initiation in patients with psoriatic arthritis decreases the risk of adverse patient outcomes and improves patients’ quality of life.

Aims. To describe a period between psoriasis and psoriatic arthritis onset and a period between psoriatic arthritis onset and diagnosis in Russian patients with moderate to severe psoriasis.

Materials and methods. Analysis of data from the psoriasis patient registry. Patients aged 18 years and older with an established diagnosis of psoriasis and psoriatic arthritis were included in the analysis. Noninclusion criteria: no data on psoriasis and/or psoriatic arthritis onset (for the period between psoriasis and psoriatic arthritis onset description); no data on psoriatic arthritis onset and/or diagnosis (for the period between psoriatic arthritis onset and diagnosis description).

Results. Sample size for the descriptive characteristic of period between psoriasis and psoriatic arthritis onset was 891 patients; sample size for the descriptive characteristic of period between psoriatic arthritis onset and diagnosis was 849 patients.

Psoriatic arthritis onset preceeded cutaneous manifestation of psoriasis in 2.5% of patients. Concurrent onset of cutaneous psoriasis and psoriatic arthritis (within one year) had 10.7% of patients. In 86.8% of patients, cutaneous manifestation of psoriasis preceded manifestation of psoriatic arthritis.

Exclusively of patients with psoriatic arthritis developed before or concurrently with cutaneous manifestation of psoriasis, the mean duration of period between psoriasis and psoriatic arthritis onset was 13.7 ± 10.3 years, the median [IQR] — 12 [6–19] years.

In 24% of patients psoriatic arthritis was diagnosed 1 year and more after its onset. The mean (±SD) period from signs and|or symptoms onset till psoriatic arthritis diagnosis was 3.9 ± 5.0 years; median [IQR] was 2 [1–4.5] years.

Conclusions. A diagnostic delay in 24% Russian patients with psoriatic arthritis is one year or more. In this subgroup of patients the mean delay in diagnosis of psoriatic arthritis is about 4 years.

Vestnik dermatologii i venerologii. 2023;99(1):48-54
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GUIDELINES FOR PRACTITIONERS

Clindamycin/benzoyl peroxid gel in mild-to-moderate acne

Olisova O.Y., Anpilogova E.M.

Abstract

Acne is a widespread inflammatory disease affecting the pilosebaceous follicles of the skin. It mostly affects teenagers and, in most cases, clinical healing occurs as patients grow up. However, 10–40% of adults may have acne tarda. Due to the fact that face is one of the favorite locations of rashes, acne significantly worsens the quality of life, as a result of which patients develop social phobia, anxiety disorders, depression and even suicidal ideas, which requires a personalized approach to prescribing highly effective treatment. According to world recommendations, regardless of the severity of acne, almost all patients are shown the use of local remedies. In our pharmaceutical market, the choice of this group of drugs is quite limited. However, in September 2022, a new drug appeared in the arsenal of Russian dermatologists, which is a combination of benzoyl peroxide and clindamycin. This review presents the accumulated experience of almost 20 years of foreign colleagues who have been successfully using a combination of benzoyl peroxide and clindamycin in the treatment of mild-to-moderate acne.

Vestnik dermatologii i venerologii. 2023;99(1):55-61
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Efficacy and safety of the first targeted biological drug dupilumab in the treatment of severe continuously relapsing atopic dermatitis

Konnov P.E., Arsenieva A.A.

Abstract

In the past few decades, the prevalence of allergic dermatoses in European countries, including the Russian Federation, has increased two to three times. The skin barrier plays an essential role in preventing the penetration of allergens and microbial agents into the human body.

Atopic dermatitis is one of the most common, genetically determined skin diseases. The development of atopic dermatitis involves environmental factors that violate the skin barrier, as well as the genetic, immunological characteristics of the patient.

In modern science, the issue of pathogenetic treatment of atopic dermatitis remains not fully resolved. The problem is compounded by the fact that this disease is multifactorial, with a predominance of IgE-mediated allergic reactions, although the level of IgE does not always correlate with the severity of atopic dermatitis.

Currently, the development and implementation of genetically engineered drugs for the treatment of this pathology continues, one of these drugs is dupilumab.

The article describes the efficacy and safety of dupilumab in the treatment of severe continuously relapsing atopic dermatitis.

Vestnik dermatologii i venerologii. 2023;99(1):62-70
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CLINICAL CASE REPORTS

A new atypical form of lipoid necrobiosis not associated with diabetes mellitus. Clinical case and a brief review of the literature

Cheboksarov D.I., Molodykh K.J., Monakhov K.N., Sokolovskiy E.V.

Abstract

The article presents a description of a clinical case of necrobiosis lipoidica complicated by ulcera-tion in a 55-year-old woman and a brief review of the literature on the topic of modern ideas about necrobiosis lipoidica. The disease manifested itself in 2005 after traumatization of the upper third of both shins as a result of a fall. The patient did visit a dermatologist office for medical help, there was a slow progression of the disease. In 2017, as a result of visiting a dermatologist office at her place of residence, she was diagnosed with necrobiosis lipoidica. The ongoing therapy with vasodi-lators and topical steroids did not lead to significant improvement. In 2021, against the background of vaccination against COVID-19 (22.07.20201 and 12.08.2021 Gam-COVID-Vac — Sputnik V) the patient notes a sharp deterioration of the process after the injection of the second component of the vaccine there were an increased in the area of lesion, ulceration. No data for diabetes mellitus were obtained during the examination. There is a history of a multi-nodular non-toxic goiter, for which a complete resection of the left lobe of the thyroid gland was performed in 1995 and a partial resection of the right lobe of the thyroid gland in 2003. The patient has been receiving L-Thyroxine replacement therapy since 2003. A biopsy of the affected skin was per-formed. The final diagnosis: necrobiosis lipoidica erythematous-ulcerative variant was established according to the pathoanatom-ic examination of the biopsy and atypical clinical picture. As a result of the therapy, the patient was discharged from the clinic with improvement.

Vestnik dermatologii i venerologii. 2023;99(1):71-80
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Granulomatous perioral dermatitis

Krasnova N.V., Gimalieva G.G., Sinitsyna L.G., Misyakova T.Y.

Abstract

Parents of patient S., born in 2018 applied with complaints of rashes on the skin of her daughter's face, accompanied by itching for a year. Topically used cream methylprednisolone aceponate and methylene blue. Objectively: the pathological process was widespread, localized on the skin of the face. On the skin of the face, congestive hyperemia, multiple miliary pustules, vesicles, already opened in places, covered with serous crusts, multiple pink papules were visualized periorally. When conducting a histological examination of the affected area of the skin of the face, characteristic signs for granulomatous dermatitis were revealed: in the follicles, foci of necrosis, macrophages with an admixture of neutrophilic leukocytes, single eosinophils and giant multinucleated cells. In the deep layers of the dermis, rough, unevenly thickened and in places multidirectional bundles of collagen fibers with signs of necrosis and the presence of giant cell granulomas, as well as numerous giant cell granulomas without necrosis, exocytosis of lymphocytes, which is characteristic of granulomatous dermatitis, were determined. The diagnosis was made: Perioral dermatitis, granulomatous form. We were prescribed a long-term oral administration of an antibiotic of the macrolide group, externally — calcineurin blockers, emollients and ointments containing zinc. On the background of the ongoing treatment, the rash resolved. There was a stable remission.

Vestnik dermatologii i venerologii. 2023;99(1):81-85
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