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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Vestnik dermatologii i venerologii</journal-id><journal-title-group><journal-title xml:lang="en">Vestnik dermatologii i venerologii</journal-title><trans-title-group xml:lang="ru"><trans-title>Вестник дерматологии и венерологии</trans-title></trans-title-group></journal-title-group><issn publication-format="print">0042-4609</issn><issn publication-format="electronic">2313-6294</issn><publisher><publisher-name xml:lang="en">Rossijskoe Obschestvo Dermatovenerologov i Kosmetologov</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">1310</article-id><article-id pub-id-type="doi">10.25208/vdv1310</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>GUIDELINES FOR PRACTITIONERS</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>В ПОМОЩЬ ПРАКТИЧЕСКОМУ ВРАЧУ</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Mechanisms of rosacea pathogenesis. A phenotypic approach to therapeutic tactics</article-title><trans-title-group xml:lang="ru"><trans-title>Механизмы патогенеза розацеа. Фенотипический подход к терапевтической тактике</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7689-8350</contrib-id><contrib-id contrib-id-type="spin">6938-4768</contrib-id><name-alternatives><name xml:lang="en"><surname>Drozhdina</surname><given-names>Marianna B.</given-names></name><name xml:lang="ru"><surname>Дрождина</surname><given-names>Марианна Борисовна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Cand. Sci. (Med.), Associate Professor</p></bio><bio xml:lang="ru"><p>к.м.н., доцент</p></bio><email>drozhdina@yandex.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2306-1423</contrib-id><contrib-id contrib-id-type="spin">2534-4480</contrib-id><name-alternatives><name xml:lang="en"><surname>Bobro</surname><given-names>Varvara A.</given-names></name><name xml:lang="ru"><surname>Бобро</surname><given-names>Варвара Андреевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Aspirant</p></bio><bio xml:lang="ru"><p>аспирант</p></bio><email>bobro.va@inbox.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Kirov State Medical University</institution></aff><aff><institution xml:lang="ru">Кировский государственный медицинский университет</institution></aff></aff-alternatives><pub-date date-type="preprint" iso-8601-date="2022-11-01" publication-format="electronic"><day>01</day><month>11</month><year>2022</year></pub-date><pub-date date-type="pub" iso-8601-date="2022-11-23" publication-format="electronic"><day>23</day><month>11</month><year>2022</year></pub-date><volume>98</volume><issue>5</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>90</fpage><lpage>97</lpage><history><date date-type="received" iso-8601-date="2022-02-23"><day>23</day><month>02</month><year>2022</year></date><date date-type="accepted" iso-8601-date="2022-10-04"><day>04</day><month>10</month><year>2022</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2022, Drozhdina M.B., Bobro V.A.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2022, Дрождина М.Б., Бобро В.А.</copyright-statement><copyright-year>2022</copyright-year><copyright-holder xml:lang="en">Drozhdina M.B., Bobro V.A.</copyright-holder><copyright-holder xml:lang="ru">Дрождина М.Б., Бобро В.А.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://vestnikdv.ru/jour/article/view/1310">https://vestnikdv.ru/jour/article/view/1310</self-uri><abstract xml:lang="en"><p>Rosacea is a widespread disease worldwide, affecting 5.5% of the human population and accompanied by a significant deterioration in the patient's quality of life. Currently, there are two classifications of rosacea, the first of which is based on a subtype approach (erythematous-telangiectatic, papulo-pustular, phimatous and ophthalmological subtypes), or on an individual analysis of the presented phenotype of rosacea. New data on the pathophysiology of rosacea have emerged, which show that genetic factors and environmental components can cause the initiation and exacerbation of rosacea due to a violation of the regulation of the innate and adaptive immune system. In addition, trigger factors can directly interact with the cutaneous nervous system and, with the help of neurovascular and neuroimmune active neuropeptides, lead to the manifestation of rosacea foci. The main mechanisms of rosacea pathogenesis are currently: activation of the immune system, disorders of neuro-immune regulation, genetic predisposition. New pathogenetic mechanisms of rosacea make it possible to continue the diagnostic search and therapeutic approaches with the personalization of management tactics for each patient, depending on the prevalence of clinical features of the course of the disease. It is necessary to evaluate the advantages and disadvantages of subtypical and phenotypic approaches to rosacea classification and choose the most optimal one. The article presents arguments on this issue, and also suggests assessing the need to switch to a new classification in order to improve the effectiveness of therapy and improve the quality of life of patients.</p></abstract><trans-abstract xml:lang="ru"><p>Розацеа — широко распространенное по всему миру заболевание, затрагивающее 5,5% человеческой популяции и сопровождающееся значительным ухудшением качества жизни пациента. В настоящее время существуют две классификации розацеа, первая из которых основана на подходе, выделяющем эритематозно-телеангиэктатический, папуло-пустулезный, фиматозный и офтальмологический подтипы, либо на индивидуальном анализе представленного фенотипа розацеа. Появились новые данные по патофизиологии розацеа, которые показывают, что генетические факторы и компоненты окружающей среды могут вызывать инициирование и обострение розацеа из-за нарушения регуляции врожденной и адаптивной иммунной системы. Помимо этого, триггерные факторы могут напрямую взаимодействовать с кожной нервной системой и с помощью нейроваскулярных и нейроиммунных активных нейропептидов приводить к проявлению розацеа. Основными механизмами патогенеза розацеа в настоящее время являются: активация иммунной системы, нарушения нейро-иммунной регуляции, генетическая предрасположенность. Выявленные новые патогенетические механизмы розацеа дают возможность продолжения диагностического поиска и терапевтических подходов с персонализацией тактики ведения применительно к каждому пациенту в зависимости от превалирования клинических особенностей течения заболевания. Необходимо оценить достоинства и недостатки подходов к классификации розацеа, основанных на выделении подтипов и фенотипов, и выбрать оптимальный из них. В статье приводятся доводы и аргументы по данной проблематике, а также предлагается оценить необходимость перехода к новой классификации с целью улучшения результативности терапии и повышения качества жизни пациентов с учетом многообразия механизмов патогенеза и клинических проявлений данного заболевания.</p></trans-abstract><kwd-group xml:lang="en"><kwd>subtypes and phenotypes of rosacea</kwd><kwd>mechanisms of pathogenesis</kwd><kwd>isotretinoin</kwd><kwd>metronidazole</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>подтипы и фенотипы розацеа</kwd><kwd>механизмы патогенеза</kwd><kwd>изотретиноин</kwd><kwd>метронидазол</kwd></kwd-group><funding-group><funding-statement xml:lang="en">The work is supported by the Pharmaceutical company LLC “JADRAN”.</funding-statement><funding-statement xml:lang="ru">Работа поддержана Фармацевтической компанией ООО «ЯДРАН».</funding-statement></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Tan J, Berg M. Rosacea: current state of epidemiology. J Am Acad Dermatol. 2013;69(6 Suppl 1):27–35. doi: 10.1016/j.jaad.2013.04.043</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Hampton PJ, Berth-Jones J, Duarte Williamson CE, Hay R, Leslie TA, Porter I, et al. British Association of Dermatologists guidelines for the management of people with rosacea 2021. Br J Dermatol. 2021;185(4):725–735. doi: 10.1111/bjd.20485</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Zhang J, Jiang P, Sheng L, Liu Y, Liu Y, Li M, et al. A Novel Mechanism of Carvedilol Efficacy for Rosacea Treatment: Toll-Like Receptor 2 Inhibition in Macrophages. Front Immunol. 2021;12:609615. doi: 10.3389/fimmu.2021.609615</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Tüzün Y, Wolf R, Kutlubay Z, Karakuş O, Engin B. Rosacea and rhinophyma. Clin Dermatol. 2014;32(1):35–46. doi: 10.1016/j.clindermatol.2013.05.024</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Walter S, Krueger S, Ho J, Reddy KK. Unilateral rhinophyma: report of a case and review. Plast Aesthet Res. 2017;4:49–53. doi:10.20517/2347-9264.2017.08</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Little SC, Stucker FJ, Compton A, Park SS. Nuances in the management of rhinophyma. Facial Plast Surg. 2012;28(2):231–237. doi: 10.1055/s-0032-1309304</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>McMahon F, Banville N, Bergin DA, Smedman C, Paulie S, Reeves E, et al. Activation of neutrophils via IP3 pathway following exposure to Demodex-associated bacterial proteins. Inflammation. 2016;39(1):425–433. doi: 10.1007/s10753-015-0264-4</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Jarmuda S, McMahon F, Żaba R, O'Reilly N, Jakubowicz O, Holland A, et al. Correlation between serum reactivity to Demodex-associated Bacillus oleronius proteins, and altered sebum levels and Demodex populations in erythematotelangiectatic rosacea patients. J Med Microbiol. 2014;63(Pt 2):258–262. doi: 10.1099/jmm.0.065136-0</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>O’Reilly N, Bergin D, Reeves EP, McElvaney NG, Kavanagh K. Demodex-associated bacterial proteins induce neutrophil activation. Br J Dermatol. 2011;166(4):753–760. doi: 10.1111/j.1365-2133.2011.10746.x</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Gomaa AHA, Yaar M, Eyada MMK, Bhawan J. Lymphangiogenesis and angiogenesis in non-phymatous rosacea. J of Cutan Pathol. 2007;34(10):748–753. doi: 10.1111/j.1600-0560.2006.00695.x</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Smith JR, Lanier VB, Braziel RM, Falkenhagen KM, White C, Rosenbaum JT. Expression of vascular endothelial growth factor and its receptors in rosacea. Br J Ophthalmol. 2007;91(2):226–229. doi: 10.1136/bjo.2006.101121</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Sener S, Akbas A, Kilinc F, Baran P, Aktas A. Thiol/disulfide homeostasis as a market of oxidative stress in rosacea: a controlled spectrophotometric study. Cutans Ocul Toxicol. 2019;38(1):55–58. doi: 10.1080/15569527.2018.1517124</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Gur TF, Erdemir AV, Gurel MS, Kocyigit A, Guler EM, Erdil D. The investigation of the relationships of Demodex density with inflammatory response and oxidative stress in rosacea. Arch Dermatol Res. 2018;310(9):759–767. doi: 10.1007/s00403-018-1857-1</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Sulk M, Seeliger S, Aubert J, Schwab VD, Cevikbas F, Rivier M, et al. Distribution and expression of non-neuronal transient receptor potential (TRPV) ion channels in rosacea. J Invest Dermatol. 2012;132(4):1253–1262. doi: 10.1038/jid.2011.424</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Buddenkotte J, Steinhoff M. Recent advances in understanding and managing rosacea. F1000Res. 2018;7:F1000 Faculty Rev-1885. doi: 10.12688/f1000research.16537.1</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Рябова В.В., Кошкин С.В., Зайцева Г.А., Евсеева А.Л. Характер распределения антигенов HLA I класса у пациентов со среднетяжелыми и тяжелыми формами акне. Иммунопатология, аллергология, инфектология. 2017;3:75–78. [Ryabova VV, Koshkin SV, Zaitseva GA, Evseeva AL. Characteristics of the distribution of class I HLA antigens in patients with moderate and severe forms of acne. Immunopathology, allergology, infectology. 2017;3:75–78. (In Russ.)]. doi: 10.14427/jipai.2017.3.75</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Chang ALS, Raber I, Xu J, Li R, Spitale R, Chen J, et al. Assessment of the genetic basis of rosacea by genome-wide association study. J Invest Dermatol. 2015;135(6):1548–1555. doi: 10.1038/jid.2015.53</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Aponte JL, Chiano MN, Yerges-Armstrong LM, Hinds DA, Tian C, Gupta A, et al. Assessment of rosacea symptom severity by genome-wide association study and expression analysis highlights immuno-inflammatory and skin pigmentation genes. Hum Mol Genet. 2018;27(15):2762–2772. doi: 10.1093/hmg/ddy184</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Woo YR, Lim JH, Cho DH, Park HJ. Rosacea: Molecular Mechanisms and Management of a Chronic Cutaneous Inflammatory Condition. Int J Mol Sci. 2016;17(9):1562. doi: 10.3390/ijms17091562</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Steensel MA van, Badeloe S, Winnepenninckx V, Vreeburg M, Steijlen PM, Geel M van. Granulomatous rosacea and Crohn's disease in a patient homozygous for the Crohn-associated NOD2/CARD15 polymorphism R702W. Exp Dermatol. 2008;17(12):1057–1058. doi: 10.1111/j.1600-0625.2008.00753.x</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Egeberg A, Hansen PR, Gislason GH, Thyssen JP. Clustering of autoimmune diseases in patients with rosacea. J Am Acad Dermatol. 2016;74(4):667–672. doi: 10.1016/j.jaad.2015.11.004</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Wilkin J, Dahl M, Detmar M, Drake L, Feinstein A, Odom R, et al. Standard classification of rosacea: Report of the National Rosacea Society Expert Committee on the Classification and Staging of Rosacea. J Am Acad Dermatol. 2002;46(4):584–587. doi: 10.1067/mjd.2002.120625</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Tan J, Almeida LMC, Bewley A, Cribier B, Dlova NC, Gallo R, et al. Updating the diagnosis, classification and assessment of rosacea: recommendations from the global ROSacea COnsensus (ROSCO) panel. Br J Dermatol. 2017;176(2):431–438. doi: 10.1111/bjd.15122</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Cribier B. Rosacea under the microscope: characteristic histological findings. J Eur Acad Dermatol Venereol. 2013;27(11):1336–1343. doi: 10.1111/jdv.1212</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Дрождина М.Б., Бобро В.А. Ринофима: тактика ведения пациента. Краткий обзор литературы и описание клинического случая. Вестник дерматологии и венерологии. 2022;98(1):64–71. [Drozhdina MB, Bobro VA. Rhinophyma: patient management. A brief review of the literature and a description of the clinical case. Vestnik dermatologii i venerologii. 2022;98(1):64–71. (In Russ.)]. doi: 10.25208/vdv1226</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Challer M, Almeida LMC, Bewley A, Cribier B, Del Rosso J, Dlova NC, et al. Recommendations for rosacea diagnosis, classification and management: update from the global ROSacea COnsensus 2019 panel. Br J Dermatol. 2020;182(5):1269–1276. doi: 10.1111/bjd.18420</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Дрождина М.Б. Фульминантные акне. Современное решение проблемы. Вестник дерматологии и венерологии. 2019;95(4):79–86. [Drozhdina MB. Fulminant acne. Modern solution to the problem. Vestnik dermatologii i venerologii. 2019;95(4):79–86. (In Russ.)]. doi: 10.25208/0042-4609-2019-95-4-79-86</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Дрождина М.Б., Бобро В.А. Подрывающий фолликулит Гоффмана — состояние проблемы, подходы к терапии, демонстрация клинических случаев. Вестник дерматологии и венерологии. 2020;96(2):35–43. [Drozhdina MB, Bobro VA. Hoffman's recalcitrant dissecting folliculitis — state of the problem, approach to therapy, demonstration of clinical cases. Vestnik dermatologii i venerologii. 2020;96(2):35–43. (In Russ.)]. doi:10.25208/vdv1139</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Дрождина М.Б. Применение Акнекутана для лечения фульминантных акне. Консилиум. Дерматовенерология. 2019;2(171):25. [Drozdina MB. The usage of Aknekutan for the treatment of fulminant acne. Consultation. Dermatovenerology. 2019;2(171):25. (In Russ.)].</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Del Rosso JQ, Tanghetti E, Webster G, Stein Gold L, Thiboutot D, Gallo RL. Update on the Management of Rosacea from the American Acne &amp; Rosacea Society (AARS). J Clin Aesthet Dermatol. 2019;12(6):17–24.</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Дрождина М.Б. Болезнь Морбигана. Современный обзор литературы. Описание редкого клинического случая. Медицинский вестник Северного Кавказа. 2020;15(1):15–21. [Drozhdina MB. Morbihan disease. A modern review of the literature. Description of a rare clinical case. Medical news of North Caucasus. 2020;15(1):129–133. (In Russ.)]. doi: 10.14300/mnnc.2020.15033</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Самцов А.В., Аравийская Е.Р. Акне и розацеа. Монография. М.: Фармтек; 2021. C. 400. [Samtsov AV, Araviiskaya EA. Akne i rozacea. Monografiya (Acne and rosacea. Мonography). Moscow: Farmtec; 2021. P. 400. (In Russ.)]</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Троянова С.Ю., Корсунская И.М., Соркина И.Л., Соболев В.В. Обоснование эффективности метронидазола в терапии розацеа. Клиническая дерматология и венерология. 2017;16(5):45–48. [Troyanova SYu, Korsunskaia IM, Sorkina IL, Sobolev VV. Justification of the efficacy of metronidazole in the treatment of rosacea. Klinicheskaya dermatologiya i venerologiya. 2017;16(5):45–48. (In Russ.)]. doi: 10.17116/klinderma201716545-4834</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Navarro-Triviño FJ, Pérez-López I, Ruíz-Villaverde R. Doxycycline, an antibiotic or an anti-inflammatory agent? The most common uses in dermatology. Actas Dermosifiliogr (Engl Ed). 2020;11(7):561–566. doi: 10.1016/j.ad.2019.12.006</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Евсеева А.Л., Рябова В.В., Кошкин С.В. Клинический случай папуло-пустулезной розацеа. Вестник дерматологии и венерологии. 2021;97(3):73–79. [Evseeva AL, Ryabova VV, Koshkin SV. A clinical case of papulo-pustular rosacea. Vestnik dermatologii i venerologii. 2021;97(3):73–79. (In Russ.)]. doi: 10.25208/vdv1228</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>Самцов А.В., Горбунов Ю.Г. Изотретиноин в лечении розацеа. Вестник дерматологии и венерологии. 2012;88(4):102–104. [Samtsov AV, Gorbunov YuV. Isotretinoin in the treatment rosacea. Vestnik dermatologii i venerologii. 2012;8(4):102–104. (In Russ.)]. doi:10.25208/vdv715</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Дрождина М.Б., Колеватых Е.П., Трубникова М.А., Кряжева П.А. Возрастные корреляции вульгарных акне. Сравнительное исследование микробиома и экспосома акне у студентов Кировского ГМУ. Анализ результатов терапии применительно к показателям качества жизни. Вестник дерматологии и венерологии. 2020;96(4):32–42. [Drozhdina MB, Kolevatykh EP, Trubnikova MA, Kryazheva PA. Age correlations of acne vulgaris. Comparative study of microbiome and acne exposom at students of Kirov state medical university. Analysis of the results of therapy applicable to indicators of quality of life. Vestnik dermatologii i venerologii. 2020;96(4):32–42. (In Russ.)]. doi: 10.25208/vdv1143-2020-96-4-32-4240</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Canavan TN, Chen E, Elewski BE. Optimizing Non-Antibiotic Treatments for Patients with Acne: A Review. Dermatol Ther (Heidelb). 2016;6(4):555–578. doi: 10.1007/s13555-016-0138-1</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Tan J, Berg M, Gallo RL, Del Rosso JQ. Applying the phenotype approach for rosacea to practice and research. Br J Dermatol. 2018;179(3):741–746. doi:10.1111/bjd.16815</mixed-citation></ref></ref-list></back></article>
