Цель. Оптимизировать подходы к диагностике и тактике ведения женщин с атрофическим вариантом течения склеротического лихена (СЛ) вульвы. Материалы и методы. Обследованы 58 пациенток с атрофическим вариантом течения СЛ вульвы от 20 до 70 лет. Контроль – 30 условно-здоровых женщин 20–70 лет. Атрофический вариант течения СЛ установлен на основании субъективных (сухость и дискомфорт в области вульвы, поверхностная вульводиния и диспареуния, легкий зуд) и объективных симптомов (выраженная атрофия тканей наружных половых органов вплоть до аплазии малых половых губ и клитора, стеноз влагалища, минимальная гипопигментация, отсутствие склероза). Определяли уровни цитокинов интерлейкина (ИЛ)-20, 23, 10, фактора некроза опухоли α, интерферона γ в периферической крови пациенток до и после иммунотерапии дезоксирибонуклеатом натрия. Результаты. У всех больных отмечалось быстрое уменьшение малых половых губ и клитора, истончение дермы и эпидермиса с их легкой травматизацией, способствующей присоединению вторичной инфекции и образованию синехий вплоть до полного сращения влагалища. Для атрофического варианта СЛ наиболее характерно возрастание ИЛ-23 (19,01 [18,0; 38,5] относительно контроля 16,6 [12,98; 20,71]), снижение уровней фактора некроза опухоли α в 2,7 раза (p<0,03), интерферона γ и ИЛ-20. Установлена иммуномодулирующая и клиническая эффективность дезоксирибонуклеата натрия. Выраженная вульводиния до лечения отмечалась у 29 (50%) пациенток, после терапии – ни у одной пациентки (0%); 44 (75,8%) пациентки после лечения отметили полное отсутствие поверхностной вульводинии, а до лечения пациентки без жалоб на вульводинию отсутствовали (0%). Легкий зуд до лечения отмечали 20 (40%) пациенток, после лечения – 2 (3,4%) пациентки. С учетом показателей цитокинов применение топических глюкокортикоидов при атрофическом варианте течения СЛ нецелесообразно, может привести к усугублению атрофии и иммуносупрессии, способствуя развитию вторичной инфекции. Заключение. Выявленные различия в содержании цитокинов у пациенток с атрофическим вариантом течения СЛ вульвы подтверждают рациональность клинической классификации СЛ по вариантам течения, обосновывают целесообразность их использования для диагностики СЛ и контроля эффективности иммунотерапии, а также предполагают дифференцированный подход к лечению различных вариантов течения СЛ с учетом влияния применяемых лекарственных средств на цитокиновый статус.
Aim.The objective is to optimize the diagnosis and management of the atrophic variant of the vulvar lichen sclerosus (LS). Materials and methods. We examined 58 female patients from 20 to 70 years old with the atrophic variant of the vulvar LS. The control group included 30 deemed healthy females 20–70 years old. The atrophic variant of LS was diagnosed based on symptoms (dryness and discomfort in the vulva, superficial vulvodynia and dyspareunia, mild itching) and signs (marked atrophy of the external genitalia tissue up to aplasia of the labia minora and clitoris, vaginal stenosis, minimal hypopigmentation, absence of sclerosis). In addition, the following cytokines were measured in the peripheral blood of patients: interleukin (IL)-20, 23, 10, tumor necrosis factor-α, and interferon-γ. The measurements were performed before and after immunotherapy with sodium deoxyribonucleate. Results. In all patients, there was a rapid shrinkage of the labia minora and clitoris, thinning and easy traumatization of the dermis and epidermis, contributing to secondary infection and synechiae formation up to complete vaginal occlusion. An increase in IL-23 (19.01 [18.0; 38.5] vs. 16.6 [12.98; 20.71] in the control group), 2.7-fold (p<0.03) decrease in tumor necrosis factor-α, interferon-γ and IL-20 are common for the atrophic variant of LS. The immunomodulatory and clinical efficacy of sodium deoxyribonucleate was demonstrated. Severe vulvodynia before treatment was noted in 29 (50%) patients and no patient (0%) after therapy; 44 (75.8%) patients reported complete reversal of superficial vulvodynia after treatment, and there were no patients without vulvodynia before treatment (0%). Mild itching before treatment was noted by 20 (40%) patients and 2 (3.4%) patients after treatment. Considering the cytokine levels, topical glucocorticoids in atrophic LS are inappropriate and can lead to atrophy and immunosuppression aggravation, contributing to the secondary infection. Conclusion. The observed differences in cytokine levels in patients with atrophic vulvar LS confirm the relevance of LS clinical classification by variants, support their use for LS diagnosis and immunotherapy efficacy control, and also suggest a differentiated approach to the treatment of different LS variants considering the effect of the drugs used on cytokine status.
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21. Christodoulou C, Choy EH. Joint inflammation and cytokine inhibition in rheumatoid arthritis. Clin Exp Med. 2006;6:13-9. DOI:10.1007/s10238-006-0088-5
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23. Федоренко Т.В., Колесникова Н.В., Пашкова И.А. Ранние цитокиновые предикторы острого отторжения трансплантата почки. Российский иммунологический журнал. 2019;13(22):590-2 [Fedorenko TV, Kolesnikova NV, Pashkova IA. Early cytokine predictors of acute kidney transplant rejection. Russian Journal of Immunology. 2019;13(22):590-2 (in Russian)]. DOI:10.31857/S102872210006984-7
24. Konrad RJ, Higgs RE, Rodgers GH, et al. Assessment and Clinical Relevance of Serum IL-19 Levels in Psoriasis and Atopic Dermatitis Using a Sensitive and Specific Novel Immunoassay. Sci Rep. 2019;9(1):5211. DOI:10.1038/s41598-019-41609-z
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27. Порсохонова Д.Ф., Рахматуллаева С.Н., Якубович А.И., Алимухамедова Ю.А. Некоторые особенности цитокинового статуса у пациенток со склероатрофическим лихеном вульвы. Актуальные вопросы дерматовенерологии, косметологии и репродуктивного здоровья. 2020:235-40 [Porsokhonova DF, Rakhmatullaeva SN, Iakubovich AI, Alimukhamedova IuA. Nekotorye osobennosti tsitokinovogo statusa u patsientok so skleroatroficheskim likhenom vul'vy. Aktual'nye voprosy dermatovenerologii, kosmetologii i reproduktivnogo zdorov'ia. 2020:235-40 (in Russian)].
28. Zemskov AM, Zemskov VM, Zemskova VA. Immunology of infections at the present stage, immunology of menopause and aging. International Journal of Recent Scientific Research. 2018;9:23416-9. DOI:10.24327/ijrsr.2018.0901.1464
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1. Kirtschig G, Becker K, Gunthert A, et al. Evidence-based (S3) Guideline on (anogenital) Lichen sclerosus. J Eur Acad Dermatol Venereol. 2015;29:1-43. DOI:10.1111/jdv.13136
2. Bleeker MC, Visser PJ, Overbeek LI, et al. Lichen Sclerosus: Incidence and Risk of Vulvar Squamous Cell Carcinoma. Cancer Epidemiol Biomarkers Prev. 2016;25(8):1224-30. DOI:10.1158/1055-9965
3. Fistarol SK, Itin PH. Diagnosis and treatment of lichen sclerosus: an update. Am J Clin Dermatol. 2013;14(1):27-47. DOI:10.1007/s40257-012-0006-4
4. Nelson DM, Peterson AC. Lichen sclerosus: epidemiological distribution in an equal access health care system. J Urol. 2011;185(2):522-5. DOI:10.1016/j.juro.2010.09.107
5. Solopova AG, Achkasov EE, Makatsariya AD, et al. Psycho-emotional profile of patients with vulvar lichen sclerosus. Obstetrics, Gynecology and Reproduction. 2020;14(2):203-10 (in Russian). DOI:10.17749/2313-7347/ob.gyn.rep.2020.106
6. Leis M, Singh A, Li C, et al. Risk of Vulvar Squamous Cell Carcinoma in Lichen Sclerosus and Lichen Planus: A Systematic Review. J Obstet Gynaecol Can. 2022;44(2):182-92. DOI: 10.1016/j.jogc.2021.09.023
7. Marfatia Y, Surani A, Baxi R. Genital lichen sclerosus et atrophicus in females: An update. Indian J Sex Transm Dis AIDS. 2019;40(1):6-12. DOI:10.4103/ijstd.IJSTD_23_19
8. Guarneri F, Giuffrida R, Di Bari F, et al. Thyroid Autoimmunity and Lichen. Front Endocrinol (Lausanne). 2017;27(8):146. DOI:10.3389/fendo.2017.00146
9. Hoang MP, Reutter J, Papalas JA, et al. Vulvar inflammatory dermatoses: an update and review. Am J Dermatopathol. 2014;36(9):689-704. DOI:10.1097/DAD.0000000000000149
10. Tran DA, Tan X, Macri CJ, et al. Lichen sclerosus: an autoimmunopathogenic and genomic enigma with emerging genetic and immune targets. Int J Biol Sci. 2019;15(7):1429-39. DOI:10.7150/ijbs.34613
11. Campanati A, Martina E, Offidani A. The Challenge Arising fr om New Knowledge about Immune and Inflammatory Skin Diseases: Wh ere We Are Today and Where We Are Going. Biomedicines. 2022;10(5):950. DOI:10.3390/biomedicines10050950
12. Filyushkina AYu, Kraposhina TP, Atanyan MА. Specific features of immune homeostasis in patients with vulvar lichen sclerosus. Russian Bulletin of Obstetrician-Gynecologist. 2015;15(1):13-7 (in Russian). DOI:10.17116/rosakush201515113-17
13. Krapf JM, Mitchell L, Holton MA, Goldstein AT. Vulvar Lichen Sclerosus: Current Perspectives. Int J Womens Health. 2020;15(12):11-20. DOI:10.2147/IJWH.S191200
14. Колесникова Е.В., Пенжоян Г.А., Жаров А.В. Клинико-морфологические и иммунологические аспекты фоновых заболеваний вульвы. Акушерство и гинекология: новости, мнения, обучение. 2019;7(2):38-41 [Kolesnikova EV, Penzhoyan GA, Zharov AV. Clinico-morphological and immunological aspects underlying diseases of the vulva. Akusherstvo i ginekologiya: novosti, mneniya, obuchenie. 2019;7(2):38-41 (in Russian)]. DOI:10.24411/ 2303-9698-2019-12004
15. Kolesnikova EV, Zharov AV, Kharitonova IA, et al. Сytokine markers for different variants of sclerotic lichen in women. Medical Immunology. 2020;22(3):551-6 (in Russian). DOI:10.15789/1563-0625-CMF-1864
16. Rutz S, Wang X, Ouyang W. The IL-20 subfamily of cytokines – from host defence to tissue homeostasis. Nat Rev Immunol. 2014;14:783-95. DOI:10.1038/nri3766
17. Simbirtsev AS. Cytokines in the pathogenesis of infectious and non-infectious human diseases. Meditsinskiy akademicheskiy zhurnal. 2013;1(3):18-41 (in Russian).
18. Blumberg X, Conklin D, Xu VF, et al. Interleukin 20: discovery, receptor identification, and role in epidermal function. Cell. 2001;104:9-19. DOI:10.1016/s0092-8674(01)00187-8
19. Yoon J, Leyva-Castillo MG, Wang G, et al. IL-23 induced in keratinocytes by endogenous TLR4 ligands polarizes dendritic cells to drive IL-22 responses to skin immunization. J Exp Med. 2016;213(10):2147-66. DOI:10.1084/jem.20150376
20. Clay FE, Cork MJ, Tarlow JK, et al. Interleukin 1 receptor antagonist gene polymorphism association with lichen sclerosus. Hum Genet. 1994;94(4):407-10. DOI:10.1007/BF00201602
21. Christodoulou C, Choy EH. Joint inflammation and cytokine inhibition in rheumatoid arthritis. Clin Exp Med. 2006;6:13-9. DOI:10.1007/s10238-006-0088-5
22. Fröhlich E, Wahl R. Thyroid autoimmunity: role of anti-thyroid antibodies in thyroid and extra-thyroidal diseases. Front Immunol. 2017;8:521. DOI:10.3389/fimmu.2017.00521
23. Fedorenko TV, Kolesnikova NV, Pashkova IA. Early cytokine predictors of acute kidney transplant rejection. Russian Journal of Immunology. 2019;13(22):590-2 (in Russian). DOI:10.31857/S102872210006984-7
24. Konrad RJ, Higgs RE, Rodgers GH, et al. Assessment and Clinical Relevance of Serum IL-19 Levels in Psoriasis and Atopic Dermatitis Using a Sensitive and Specific Novel Immunoassay. Sci Rep. 2019;9(1):5211. DOI:10.1038/s41598-019-41609-z
25. Patrushev AV, Samtsov AV, Soukharev A. Features of the cytokine profile and the effectiveness of radical treatment of focal infection in patients with psoriasis. Vestnik dermatologii i venerologii. 2021;97(2):32-40 (in Russian). DOI:10.25208/vdv1200
26. Romanova NV, Shilkina NP, Kaprel'iants EIu, Romanov VA. Immunopatologicheskie narusheniia i tsitokinovyi profil' pri sistemnoi i ogranichennoi sklerodermii. Terapevticheskii Arkhiv (Ter. Arkh.). 2012;84(5):28-31 (in Russian).
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