vspВопросы современной педиатрииCurrent Pediatrics1682-55271682-5535Издательство «ПедиатрЪ»10.15690/vsp.v19i6.2145vsp-2504Research ArticleОБЗОР ЛИТЕРАТУРЫREVIEWБиологическая терапия среднетяжелых и тяжелых форм атопического дерматита в детском возрастеBiologic Therapy of Moderate and Severe Forms of Atopic Dermatitis in Childrenhttps://orcid.org/0000-0003-2252-8570МурашкинН. Н.MurashkinNikolay N.

Мурашкин Николай Николаевич, доктор медицинских наук, заведующий отделением дерматологии с группой лазерной хирургии, заведующий лабораторией патологии кожи у детей отдела научных исследований в педиатрии НМИЦ здоровья детей, профессор кафедры дерматовенерологии и косметологии ЦГМА, профессор кафедры педиатрии и детской ревматологии Первого МГМУ им. И.М. Сеченова

119296, Москва, Ломоносовский пр-т, д. 2, стр. 1

m_nn2001@mail.ruhttps://orcid.org/0000-0002-2209-7531Намазова-БарановаЛ. С.Namazova-BaranovaLeyla S.ОпрятинЛ. А.OpryatinLeonid A.https://orcid.org/0000-0002-4107-4642ЕпишевР. В.EpishevRoman V.https://orcid.org/0000-0002-6034-8231МатерикинА. И.MaterikinAlexander I.https://orcid.org/0000-0002-8232-8936АмбарчянЭ. Т.AmbarchianEduard T.https://orcid.org/0000-0002-0081-0981ИвановР. А.IvanovRoman A.https://orcid.org/0000-0001-9777-0156ФёдоровД. В.FedorovDmitriy V.https://orcid.org/0000-0002-8268-069XКуколеваД. С.KukolevaDaria S.Национальный медицинский исследовательский центр здоровья детей; Первый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский Университет); Центральная государственная медицинская академия Управления делами Президента РФ; НИИ педиатрии и охраны здоровья детей ЦКБ РАНРоссияNational Medical Research Center of Children’s Health; Sechenov First Moscow State Medical University (Sechenov University); Central State Medical Academy of Department of Presidential Affairs; Research Institute of Pediatrics and Children’s Health in “Central Clinical Hospital of the Russian Academy of Sciences”Russian FederationНИИ педиатрии и охраны здоровья детей ЦКБ РАН; Российский национальный исследовательский медицинский университет им. Н.И. ПироговаРоссияResearch Institute of Pediatrics and Children’s Health in “Central Clinical Hospital of the Russian Academy of Sciences”; Pirogov Russian National Research Medical UniversityRussian FederationНациональный медицинский исследовательский центр здоровья детейРоссияNational Medical Research Center of Children’s HealthRussian Federation202025122020196432443Copyright © Мурашкин Н.Н., Намазова-Баранова Л.С., Опрятин Л.А., Епишев Р.В., Материкин А.И., Амбарчян Э.Т., Иванов Р.А., Фёдоров Д.В., Куколева Д.С., 20202020Мурашкин Н.Н., Намазова-Баранова Л.С., Опрятин Л.А., Епишев Р.В., Материкин А.И., Амбарчян Э.Т., Иванов Р.А., Фёдоров Д.В., Куколева Д.С.Murashkin N.N., Namazova-Baranova L.S., Opryatin L.A., Epishev R.V., Materikin A.I., Ambarchian E.T., Ivanov R.A., Fedorov D.V., Kukoleva D.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vsp.spr-journal.ru/jour/article/view/2504

Атопический дерматит (АтД) — заболевание, характеризующееся хроническим воспалением, дисфункцией эпидермального барьера и микробным дисбиозом. АтД широко распространен, в том числе в детской популяции. В статье обсуждены патогенетические основы заболевания: неполноценность кожного барьера, иммунологические причины хронического воспаления, характеристика нормального кожного микробиома и его нарушения как на пораженной, так и на непораженной коже детей с АтД. Рассмотрены основные принципы системной терапии среднетяжелых и тяжелых форм заболевания. Обсуждены особенности таргетной терапии пациентов детского возраста со среднетяжелой и тяжелой формой АтД ингибитором IL 4/IL 13 — препаратом дупилумаб. Приводится обзор результатов исследований эффективности и безопасности дупилумаба.

Atopic dermatitis (AD) is the disease with chronic inflammation, epidermal barrier dysfunction and microbial dysbiosis. AD is widespread, including pediatric population. The article discusses the disease’s pathogenesis: skin barrier deficiency, immunological causes of chronic inflammation, characteristics of normal skin microbiome and its disorders on both affected and unaffected skin of children with AD. Main principles of systemic treatment for moderate and severe forms of disease are considered. Features of targeted therapy with dupilumab (IL 4/IL 13 inhibitor) in children with moderate and severe forms of AD are discussed. The overview of the research results on the dupilumab efficacy and safety is presented.

атопический дерматиткожный барьермикробиом кожидупилумабдетиatopic dermatitisskin barriercutaneous microbiomedupilumabchildrenНе указанNot specifiedReferencesEichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for the management of atopic dermatitis. J Am Acad Dermatol. 2014; 70(2):338–351. doi: 10.1016/j.jaad.2013.10.010.Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for the management of atopic dermatitis. J Am Acad Dermatol. 2014; 70(2):338–351. doi: 10.1016/j.jaad.2013.10.010.Odhiambo JA, Williams HC, Clayton TO, et al. Global variations in prevalence of eczema symptoms in children from ISAAC Phase Three. J Allergy Clin Immunol. 2009;124(6):1251–1258.e23. doi: 10.1016/j.jaci.2009.10.009.Odhiambo JA, Williams HC, Clayton TO, et al. Global variations in prevalence of eczema symptoms in children from ISAAC Phase Three. J Allergy Clin Immunol. 2009;124(6):1251–1258.e23. doi: 10.1016/j.jaci.2009.10.009.Ресурсы и деятельность медицинских организаций дер матовенерологического профиля. Заболеваемость инфекция ми, передаваемыми половым путем, заразными кожными болезнями и заболеваниями кожи за 2017–2018 годы. М.; 2019. С. 121–123.Resursy i deyatel’nost’ meditsinskikh organizatsii dermatovenerologicheskogo profilya. Zabolevaemost’ infektsiyami, peredavaemymi polovym putem, zaraznymi kozhnymi boleznyami i zabolevaniyami kozhi za 2017–2018 gody. Moscow; 2019. pp. 121–123. (In Russ).Намазова-Баранова Л .С., Баранов А.А., Кубанова А.А. и др. Атопический дерматит у детей: современные клинические рекомендации по диагностике и терапии // Вопросы современной педиатрии. — 2016. — Т. 15. — № 3. — С. 279–293. doi: 10.15690/vsp.v15i3.1566.Namazova-Baranova LS, Baranov AA, Kubanova AA., et al. Atopic Dermatitis in Children: Current Clinical Guidelines for Diagnosis and Therapy. Voprosy sovremennoi pediatrii — Current Pediatrics. 2016;15(3):279–294. (In Russ). doi: 10.15690/vsp.v15i3.1566.Pols DHJ, Wartna JB , Moed H, et al. Atopic dermatitis, asthma and allergic rhinitis in general practice and the open population: a systematic review. Scand J Prim Health Care. 2016;34(2): 143–150. doi: 10.3109/02813432.2016.1160629.Pols DHJ, Wartna JB , Moed H, et al. Atopic dermatitis, asthma and allergic rhinitis in general practice and the open population: a systematic review. Scand J Prim Health Care. 2016;34(2): 143–150. doi: 10.3109/02813432.2016.1160629.Hill DA, Spergel JM . The Atopic March: Critical Evidence and Clinical Relevance. Ann Allergy Asthma Immunol. 2018;120(2): 131–137. doi: 10.1016/j.anai.2017.10.037.Hill DA, Spergel JM . The Atopic March: Critical Evidence and Clinical Relevance. Ann Allergy Asthma Immunol. 2018;120(2): 131–137. doi: 10.1016/j.anai.2017.10.037.Bieber T. Atopic De rmatitis. N Eng J Med. 2008;358(14): 1483–1494. doi: 10.1056/NEJMra074081.Bieber T. Atopic De rmatitis. N Eng J Med. 2008;358(14): 1483–1494. doi: 10.1056/NEJMra074081.Leung DY, Guttman-Y assky E. Deciphering the complexities of atopic dermatitis: shifting paradigms in treatment approaches. J Allergy Clin Immunol. 2014;134(4):769–79. doi: 10.1016/j.jaci.2014.08.008.Leung DY, Guttman-Y assky E. Deciphering the complexities of atopic dermatitis: shifting paradigms in treatment approaches. J Allergy Clin Immunol. 2014;134(4):769–79. doi: 10.1016/j.jaci.2014.08.008.Schmid-Grendelmeier P, Fluckiger S, Disch R, et al. IgE-me diated and T cell-mediated autoimmunity against manganese superoxide dismutase in atopic dermatitis. J Allergy Clin Immunol. 2005;115(5): 1068–1075. doi: 10.1016/j.jaci.2005.01.065.Schmid-Grendelmeier P, Fluckiger S, Disch R, et al. IgE-me diated and T cell-mediated autoimmunity against manganese superoxide dismutase in atopic dermatitis. J Allergy Clin Immunol. 2005;115(5): 1068–1075. doi: 10.1016/j.jaci.2005.01.065.Мурашкин Н.Н., Епиш ев Р.В., Фёдоров Д.В. и др. Синдром чувствительной кожи при атопическом дерматите у детей: особенности патогенеза и терапевтической тактики // Вопросы современной педиатрии. — 2019. — Т. 18. — № 4. — С. 285–293. doi: 10.15690/vsp.v18i4.2046.Murashkin NN, Epishev RV, Fedorov DV, et al. Sensitive Skin Syndrome in Children with Atopic Dermatitis: Pathogenesis and Management Features. Voprosy sovremennoi pediatrii — Current Pediatrics. 2019;18(4):285–293. (In Russ). doi: 10.15690/vsp.v18i4.2046.Bunikowski R, Mielk e M, Skarabis H, et al. Prevalence and role of serum IgE antibodies to the Staphylococcus aureus-derived superantigens SEA and SEB in children with atopic dermatitis. J Allergy Clin Immunol. 1999;103(1 Pt 1):119–124. doi: 10.1016/s0091-6749(99)70535-x.Bunikowski R, Mielk e M, Skarabis H, et al. Prevalence and role of serum IgE antibodies to the Staphylococcus aureus-derived superantigens SEA and SEB in children with atopic dermatitis. J Allergy Clin Immunol. 1999;103(1 Pt 1):119–124. doi: 10.1016/s0091-6749(99)70535-x.Paus R, Schmelz M, Biro T, Steinhoff M. Frontiers in pruritus research: scratching the brain for more effective itch therapy. J Clin Invest. 2006;116(5):1174–1186. doi: 10.1172/JCI28553.Paus R, Schmelz M, Biro T, Steinhoff M. Frontiers in pruritus research: scratching the brain for more effective itch therapy. J Clin Invest. 2006;116(5):1174–1186. doi: 10.1172/JCI28553.Artis D, Spits H. T he biology of innate lymphoid cells. Nature. 2015;517(7534):293–301. doi: 10.1038/nature14189.Artis D, Spits H. T he biology of innate lymphoid cells. Nature. 2015;517(7534):293–301. doi: 10.1038/nature14189.Clark RA. Skin-Resi dent T Cells: The Ups and Downs of On Site Immunity. J Invest Dermatol. 2010;130(2):362–370. doi: 10.1038/jid.2009.247.Clark RA. Skin-Resi dent T Cells: The Ups and Downs of On Site Immunity. J Invest Dermatol. 2010;130(2):362–370. doi: 10.1038/jid.2009.247.Szabo PA, Miron M, Farber DL. Location, location, location: Tissue resident memory T cells in mice and humans. Sci Immunol. 2019;4(34):eaas9673. doi: 10.1126/sciimmunol.aas9673.Szabo PA, Miron M, Farber DL. Location, location, location: Tissue resident memory T cells in mice and humans. Sci Immunol. 2019;4(34):eaas9673. doi: 10.1126/sciimmunol.aas9673.Gollwitzer ES, Mars land BJ. Impact of Early-Life Exposures on Immune Maturation and Susceptibility to Disease. Trends Immunol. 2015;36(11):684–696. doi: 10.1016/j.it.2015.09.009.Gollwitzer ES, Mars land BJ. Impact of Early-Life Exposures on Immune Maturation and Susceptibility to Disease. Trends Immunol. 2015;36(11):684–696. doi: 10.1016/j.it.2015.09.009.Wynn TA. Type 2 cyt okines: mechanisms and therapeutic strategies. Nat Rev Immunol. 2015;15(5):271–282. doi: 10.1038/nri3831.Wynn TA. Type 2 cyt okines: mechanisms and therapeutic strategies. Nat Rev Immunol. 2015;15(5):271–282. doi: 10.1038/nri3831.Gandhi NA, Pirozzi G, Graham NMH. Commonality of the IL-4/IL-13 pathway in atopic diseases. Expert Rev Clin Immunol. 2017;13(5):425–437. doi: 10.1080/1744666X.2017.1298443.Gandhi NA, Pirozzi G, Graham NMH. Commonality of the IL-4/IL-13 pathway in atopic diseases. Expert Rev Clin Immunol. 2017;13(5):425–437. doi: 10.1080/1744666X.2017.1298443.LaPorte SL, Juo ZS, Vaclavikova J, et al. Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system. Cell. 2008;132(2):259–272. doi: 10.1016/j.cell.2007.12.030.LaPorte SL, Juo ZS, Vaclavikova J, et al. Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system. Cell. 2008;132(2):259–272. doi: 10.1016/j.cell.2007.12.030.Paul WE, Zhu J. How are T(H)2-type immune responses initiated and amplified? Nat Rev Immunol. 2010;10(4):225–235. doi: 10.1038/nri2735.Paul WE, Zhu J. How are T(H)2-type immune responses initiated and amplified? Nat Rev Immunol. 2010;10(4):225–235. doi: 10.1038/nri2735.Licari A, Castagnol i R, Marseglia A, et al. Dupilumab to Treat Type 2 Inflammatory Diseases in Children and Adolescents. Paediatric Drugs. 2020;22(3):295–310. doi: 10.1007/s40272-020-00387-2.Licari A, Castagnol i R, Marseglia A, et al. Dupilumab to Treat Type 2 Inflammatory Diseases in Children and Adolescents. Paediatric Drugs. 2020;22(3):295–310. doi: 10.1007/s40272-020-00387-2.Nelms K, Keegan AD, Zamorano J, et al. The IL-4 receptor: signaling mechanisms and biologic functions. Annu Rev Immunol. 1999;17:701–738. doi: 10.1146/annurev.immunol.17.1.701.Nelms K, Keegan AD, Zamorano J, et al. The IL-4 receptor: signaling mechanisms and biologic functions. Annu Rev Immunol. 1999;17:701–738. doi: 10.1146/annurev.immunol.17.1.701.Chiaramonte MG, Men tink-Kane M, Jacobson BA, et al. Regulation and function of the interleukin 13 receptor alpha 2 during a T helper cell type 2-dominant immune response. J Exp Med. 2003;197(6):687–701. doi: 10.1084/jem.20020903.Chiaramonte MG, Men tink-Kane M, Jacobson BA, et al. Regulation and function of the interleukin 13 receptor alpha 2 during a T helper cell type 2-dominant immune response. J Exp Med. 2003;197(6):687–701. doi: 10.1084/jem.20020903.Wood N, Whitters MJ , Jacobson BA, et al. Enhanced interleukin (IL)-13 responses in mice lacking IL-13 receptor alpha 2. J Exp Med. 2003;197(6):703–709. doi: 10.1084/jem.20020906.Wood N, Whitters MJ , Jacobson BA, et al. Enhanced interleukin (IL)-13 responses in mice lacking IL-13 receptor alpha 2. J Exp Med. 2003;197(6):703–709. doi: 10.1084/jem.20020906.Круглова Л.С., Генслер Е.М. Атопический дерматит: новые горизонты терапии // Медицинский Алфавит. Дерматология. — 2019. — Т. 1. — № 7(382). — С. 29–32. doi: 10.33667/2078-5631-2019-1-7(382)-29-32.Kruglova LS, Gensler EM. Atopic dermatitis: new horizons of therapy. Medical Alphabet. Dermatology. 2019;1(7):29–32. (In Russ). doi: 10.33667/2078-5631-2019-1-7(382)-29-32.Tanaka Y, Hamano S, Gotoh K, et al. T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor-alpha subunit controlled by the Rac activator Dock2. Nat Immunol. 2007;8(10):1067–1075. doi: 10.1038/ni1506.Tanaka Y, Hamano S, Gotoh K, et al. T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor-alpha subunit controlled by the Rac activator Dock2. Nat Immunol. 2007;8(10):1067–1075. doi: 10.1038/ni1506.Noval Rivas M, Burt on OT, Wise P, et al. Regulatory T cell reprogramming toward a Th2-cell-like lineage impairs oral tolerance and promotes food allergy. Immunity. 2015;42(3):512–523. doi: 10.1016/j.immuni.2015.02.004.Noval Rivas M, Burt on OT, Wise P, et al. Regulatory T cell reprogramming toward a Th2-cell-like lineage impairs oral tolerance and promotes food allergy. Immunity. 2015;42(3):512–523. doi: 10.1016/j.immuni.2015.02.004.Hershey GK, Friedri ch MF, Esswein LA, et al. The association of atopy with a gain-of-function mutation in the alpha subunit of the interleukin-4 receptor. N Engl J Med. 1997;337(24):1720–1725. doi: 10.1056/NEJM199712113372403.Hershey GK, Friedri ch MF, Esswein LA, et al. The association of atopy with a gain-of-function mutation in the alpha subunit of the interleukin-4 receptor. N Engl J Med. 1997;337(24):1720–1725. doi: 10.1056/NEJM199712113372403.Gittler JK, Shemer A, Suarez-Farinas M, et al. Progressive activation of TH2/TH22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J Allergy Clin Immunol. 2012;130(6):1344–1354. doi: 10.1016/j.jaci.2012.07.012.Gittler JK, Shemer A, Suarez-Farinas M, et al. Progressive activation of TH2/TH22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J Allergy Clin Immunol. 2012;130(6):1344–1354. doi: 10.1016/j.jaci.2012.07.012.Honzke S, Wallmeyer L, Ostrowski A, et al. Influence of Th2 Cytokines on the Cornified Envelope, Tight Junction Proteins, and -Defensins in Filaggrin-Deficient Skin Equivalents. J Invest Dermatol. 2016;136(3):631–639. doi: 10.1016/j.jid.2015.11.007.Honzke S, Wallmeyer L, Ostrowski A, et al. Influence of Th2 Cytokines on the Cornified Envelope, Tight Junction Proteins, and -Defensins in Filaggrin-Deficient Skin Equivalents. J Invest Dermatol. 2016;136(3):631–639. doi: 10.1016/j.jid.2015.11.007.Huang YJ, Marsland BJ, Bunyavanich S. et al. The microbiome in allergic disease: Current understanding and future opportunities-2017 PRACTALL document of the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy and Clinical Immunology. J Allergy Clin Immunol. 2017; 139(4):1099–1110. doi: 10.1016/j.jaci.2017.02.007.Huang YJ, Marsland BJ, Bunyavanich S. et al. The microbiome in allergic disease: Current understanding and future opportunities-2017 PRACTALL document of the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy and Clinical Immunology. J Allergy Clin Immunol. 2017; 139(4):1099–1110. doi: 10.1016/j.jaci.2017.02.007.Мурашкин Н.Н., Материкин А.И., Опрятин Л.А. и др. Особенности микробиома кожи у детей с атопическим дерматитом и новые возможности для патогенетической терапии // Педиатрическая фармакология. — 2019. — Т. 16. — № 5. — С. 304–309. doi: 10.15690/pf.v16i5.2060.Murashkin NN, Materikin AI, Opryatin LA, et al. Features of Cutaneous Microbiome in Children With Atopic Dermatitis and New Pathogenetic Therapy Options. Pediatricheskaya farmakologiya — Pediatric pharmacology. 2019;16(5):304–309. (In Russ). doi: 10.15690/pf.v16i5.2060.Yosipovitch G, Papo iu ADP. What causes itch in atopic dermatitis? Curr Allergy Asthma Reps. 2008;8(4):306–311. doi: 10.1007/s11882-008-0049-z.Yosipovitch G, Papo iu ADP. What causes itch in atopic dermatitis? Curr Allergy Asthma Reps. 2008;8(4):306–311. doi: 10.1007/s11882-008-0049-z.Oetjen LK, Mack MR, Feng J, et al. Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch. Cell. 2017;171(1):217–228.e13. doi: 10.1016/j.cell.2017.08.006.Oetjen LK, Mack MR, Feng J, et al. Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch. Cell. 2017;171(1):217–228.e13. doi: 10.1016/j.cell.2017.08.006.Czarnowicki T, He H , Krueger JG, Guttman-Yassky E. Atopic derma titis endotypes and implications for targeted therapeutics. J Allergy Clin Immunol. 2019;143(1):1–11. doi: 10.1016/j.jaci.2018.10.032.Czarnowicki T, He H , Krueger JG, Guttman-Yassky E. Atopic derma titis endotypes and implications for targeted therapeutics. J Allergy Clin Immunol. 2019;143(1):1–11. doi: 10.1016/j.jaci.2018.10.032.Lowe AJ, Leung DY M, Tang MLK, et al. The skin as a target for prevention of the atopic march. Ann Allergy Asthma Immunol. 2018;120(2):145–151. doi: 10.1016/j.anai.2017.11.023.Lowe AJ, Leung DY M, Tang MLK, et al. The skin as a target for prevention of the atopic march. Ann Allergy Asthma Immunol. 2018;120(2):145–151. doi: 10.1016/j.anai.2017.11.023.Brunner PM, Suarez- Farinas M, He H, et al. The atopic dermatitis blood signature is characterized by increases in inflammatory and cardiovascular risk proteins. Sci Rep. 2017;7(1):8701. doi: 10.1038/s41598-017-09207-z.Brunner PM, Suarez- Farinas M, He H, et al. The atopic dermatitis blood signature is characterized by increases in inflammatory and cardiovascular risk proteins. Sci Rep. 2017;7(1):8701. doi: 10.1038/s41598-017-09207-z.Ungar B, Garcet S, Gonzalez J, et al. An Integrated Model of Atopic Dermatitis Biomarkers Highlights the Systemic Nature of the Disease. J Investe Dermatol. 2017;137(3):603–613. doi: 10.1016/j.jid.2016.09.037.Ungar B, Garcet S, Gonzalez J, et al. An Integrated Model of Atopic Dermatitis Biomarkers Highlights the Systemic Nature of the Disease. J Investe Dermatol. 2017;137(3):603–613. doi: 10.1016/j.jid.2016.09.037.Thibodeaux Q, Smith MP, Ly K, et al. A review of dupilumab in the treatment of atopic diseases. Hum Vaccin Immunother. 2019;15(9):2129–2139. doi: 10.1080/21645515.2019.1582403.Thibodeaux Q, Smith MP, Ly K, et al. A review of dupilumab in the treatment of atopic diseases. Hum Vaccin Immunother. 2019;15(9):2129–2139. doi: 10.1080/21645515.2019.1582403.Del Rosso JQ. Monoc lonal antibody therapies for atopic dermatitis: where are we now in the spectrum of disease mana gement? J Clin Aesthet Dermatol. 2019;12(2):39–41.Del Rosso JQ. Monoc lonal antibody therapies for atopic dermatitis: where are we now in the spectrum of disease mana gement? J Clin Aesthet Dermatol. 2019;12(2):39–41.Wang L-H, Xue Y, Mu rphy A, Stevens S. Humanized IL-4 and IL-4R alpha animals. Patent. Publication Number WO/2015/171861. Publication Date 12.11.2015. International Application No. PCT/ US2015/029638. International Filing Date 07.05.2015. US.Wang L-H, Xue Y, Mu rphy A, Stevens S. Humanized IL-4 and IL-4R alpha animals. Patent. Publication Number WO/2015/171861. Publication Date 12.11.2015. International Application No. PCT/ US2015/029638. International Filing Date 07.05.2015. US.Kostic A, Kelly L, Liu X, Classon BJ. Methods for treating eosinophilic esophagitis by administering an IL-4r inhibitor. Patent. Publication Number WO/2015/006571. Publication Date 15.01.2015. International Application No. PCT/US2014/046170. International Filing Date 10.07.2014. US.Kostic A, Kelly L, Liu X, Classon BJ. Methods for treating eosinophilic esophagitis by administering an IL-4r inhibitor. Patent. Publication Number WO/2015/006571. Publication Date 15.01.2015. International Application No. PCT/US2014/046170. International Filing Date 10.07.2014. US.Simpson EL, Paller AS, Siegfried EC, et al Efficacy and Safety of Dupilumab in Adolescents With Uncontrolled Moderate to Severe Atopic Dermatitis: A Phase 3 Randomized Clinical Trial. JAMA Dermatol. 2020;156(1):44–56. doi: 10.1001/jamadermatol.2019.3336.Simpson EL, Paller AS, Siegfried EC, et al Efficacy and Safety of Dupilumab in Adolescents With Uncontrolled Moderate to Severe Atopic Dermatitis: A Phase 3 Randomized Clinical Trial. JAMA Dermatol. 2020;156(1):44–56. doi: 10.1001/jamadermatol.2019.3336.de Bruin-Weller M, Thaci D, Smith CH, et al. Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebocontrolled, randomized phase III clinical trial (LIBERTY AD CAFE). Br J Dermatol. 2018;178(5):1083–1101. doi: 10.1111/bjd.16156.de Bruin-Weller M, Thaci D, Smith CH, et al. Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebocontrolled, randomized phase III clinical trial (LIBERTY AD CAFE). Br J Dermatol. 2018;178(5):1083–1101. doi: 10.1111/bjd.16156.Regeneron Pharmaceuticals. Study to Investigate the Efficacy and Safety of Dupilumab Administered With Topical Corticosteroids (TCS) in Participants 6 to < 12 Years With Severe Atopic Dermatitis (AD). ClinicalTrials. gov. August 13, 2020. Available online: https://clinicaltrials.gov/ct2/show/study/NCT03345914. Accessed on September 12, 2020.Regeneron Pharmaceuticals. Study to Investigate the Efficacy and Safety of Dupilumab Administered With Topical Corticosteroids (TCS) in Participants 6 to < 12 Years With Severe Atopic Dermatitis (AD). ClinicalTrials. gov. August 13, 2020. Available online: https://clinicaltrials.gov/ct2/show/study/NCT03345914. Accessed on September 12, 2020.Callewaert C, Nakat suji T, Knight R, et al. IL-4R Blockade by Dupilumab Decreases Staphylococcus aureus Colonization and Increases Microbial Diversity in Atopic Dermatitis. J Invest Dermatol. 2020;140(1):191–202.e7. doi: 10.1016/j.jid.2019.05.024.Callewaert C, Nakat suji T, Knight R, et al. IL-4R Blockade by Dupilumab Decreases Staphylococcus aureus Colonization and Increases Microbial Diversity in Atopic Dermatitis. J Invest Dermatol. 2020;140(1):191–202.e7. doi: 10.1016/j.jid.2019.05.024.Severity scoring of atopic dermatitis: The SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology. 1993;186(1):23–31. doi: 10.1159/000247298.Severity scoring of atopic dermatitis: The SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology. 1993;186(1):23–31. doi: 10.1159/000247298.Barbier N, Paul C, Luger T, et al. Validation of the Eczema Area and Severity Index for atopic dermatitis in a cohort of 1550 patients from the pimecrolimus cream 1% randomized controlled clinical trials programme. Br J Dermatol. 2004;150(1):96–102. doi: 10.1111/j.1365-2133.2004.05696.x.Barbier N, Paul C, Luger T, et al. Validation of the Eczema Area and Severity Index for atopic dermatitis in a cohort of 1550 patients from the pimecrolimus cream 1% randomized controlled clinical trials programme. Br J Dermatol. 2004;150(1):96–102. doi: 10.1111/j.1365-2133.2004.05696.x.Waters A, Sandhu D, Beattie P, et al. Severity stratification of Children’s Dermatology Life Quality Index (CDLQI) scores. Br J Dermatol. 2010;163(Suppl 1):121.Waters A, Sandhu D, Beattie P, et al. Severity stratification of Children’s Dermatology Life Quality Index (CDLQI) scores. Br J Dermatol. 2010;163(Suppl 1):121.Lewis-Jones MS, Fin lay AY, Dykes PJ. The Infants’ Dermatitis Quality of Life Index. Br J Dermatol. 2001;144(1):104–110. doi: 10.1046/j.1365-2133.2001.03960.x.Lewis-Jones MS, Fin lay AY, Dykes PJ. The Infants’ Dermatitis Quality of Life Index. Br J Dermatol. 2001;144(1):104–110. doi: 10.1046/j.1365-2133.2001.03960.x.Basra MKA, Sue-Ho R , Finlay AY. The Family Dermatology Life Quality Index: measuring the secondary impact of skin disease. Br J Dermatol. 2007;156(3):528–538. doi: 10.1111/j.1365-2133.2006.07617.x.Basra MKA, Sue-Ho R , Finlay AY. The Family Dermatology Life Quality Index: measuring the secondary impact of skin disease. Br J Dermatol. 2007;156(3):528–538. doi: 10.1111/j.1365-2133.2006.07617.x.Lee JY, Kim M, Yang H-K, et al. Reliability and validity of the Atopic Dermatitis Symptom Score (ADSS). Pediatr Allergy Immunol. 2018;29(3):290–295. doi: 10.1111/pai.12865.Lee JY, Kim M, Yang H-K, et al. Reliability and validity of the Atopic Dermatitis Symptom Score (ADSS). Pediatr Allergy Immunol. 2018;29(3):290–295. doi: 10.1111/pai.12865.Cella D, Yount S, R othrock N, et al. The Patient-Reported Outcomes Measurement Information System (PROMIS). Med Care. 2007;45(Suppl 1):S3–S11. doi: 10.1097/01.mlr.0000258615.Cella D, Yount S, R othrock N, et al. The Patient-Reported Outcomes Measurement Information System (PROMIS). Med Care. 2007;45(Suppl 1):S3–S11. doi: 10.1097/01.mlr.0000258615.Posner K, Brown GK, Stanley B, et al. The Columbia–Suicide Severity Rating Scale: Initial Validity and Internal Consistency Findings From Three Multisite Studies With Adolescents and Adults. Am J Psychiatry. 2011;168(12):1266–1277. doi: 10.1176/appi.ajp.2011.10111.Posner K, Brown GK, Stanley B, et al. The Columbia–Suicide Severity Rating Scale: Initial Validity and Internal Consistency Findings From Three Multisite Studies With Adolescents and Adults. Am J Psychiatry. 2011;168(12):1266–1277. doi: 10.1176/appi.ajp.2011.10111.Matsunaga K, Katoh N, Fujieda S, et al. Dupilumab: Basic aspects and applications to allergic diseases. Allergol Int. 2020;69(2): 187–196. doi: 10.1016/j.alit.2020.01.002.Matsunaga K, Katoh N, Fujieda S, et al. Dupilumab: Basic aspects and applications to allergic diseases. Allergol Int. 2020;69(2): 187–196. doi: 10.1016/j.alit.2020.01.002.Мурашкин Н.Н., Материкин А.И., Амбарчян Э.Т., Епишев Р.В. Современные представления о патогенезе и принципах наружной терапии атопического дерматита у детей // Вопросы современной педиатрии. — 2016. — Т. 15. — № 6. — С. 584–589. doi: 1010.15690/vsp.v15i6.1655.Murashkin NN, Materikin AI, Ambarchyan ET, Epishev RV. Current Views on the Pathogenesis and Principles of External Treatment of Atopic Dermatitis in Children. Voprosy sovremennoi pediatrii — Current Pediatrics. 2016;15(6):584–589. (In Russ). doi: 1010.15690/vsp.v15i6.1655.Coondoo A, Phiske M , Verma S, Lahiri K. Side-effects of topical steroids: A long overdue revisit. Indian Dermatol Online J. 2014;5(4): 416–425. doi: 10.4103/2229-5178.142483.Coondoo A, Phiske M , Verma S, Lahiri K. Side-effects of topical steroids: A long overdue revisit. Indian Dermatol Online J. 2014;5(4): 416–425. doi: 10.4103/2229-5178.142483.Megna M, Napolitano M, Patruno C, et al. Systemic Treatment of Adult Atopic Dermatitis: A Review. Dermatol Ther. 2016;7(1):1–23. doi: 10.1007/s13555-016-0170-1.Megna M, Napolitano M, Patruno C, et al. Systemic Treatment of Adult Atopic Dermatitis: A Review. Dermatol Ther. 2016;7(1):1–23. doi: 10.1007/s13555-016-0170-1.Patrizi A, Raone B, Ravaioli GM. Management of atopic derma titis: safety and efficacy of phototherapy. Clin Cosmet Investig Dermatol. 2015;8:511–520. doi: 10.2147/ccid.s87987.Patrizi A, Raone B, Ravaioli GM. Management of atopic derma titis: safety and efficacy of phototherapy. Clin Cosmet Investig Dermatol. 2015;8:511–520. doi: 10.2147/ccid.s87987.Ivert LU, Wahlgren CF, Ivert L, et al. Eye complications during dupilumab treatment for severe atopic dermatitis. Acta Derm Venereol. 2019;99(4):375–378. doi: 10.2340/00015555-3121.Ivert LU, Wahlgren CF, Ivert L, et al. Eye complications during dupilumab treatment for severe atopic dermatitis. Acta Derm Venereol. 2019;99(4):375–378. doi: 10.2340/00015555-3121.Wenzel S, Ford L, P earlman D, et al., Dupilumab in per sistent asthma with elevated eosinophil levels. N Engl J Med. 2013; 368(26):2455–2466. doi: 10.1056/NEJMoa1304048.Wenzel S, Ford L, P earlman D, et al., Dupilumab in per sistent asthma with elevated eosinophil levels. N Engl J Med. 2013; 368(26):2455–2466. doi: 10.1056/NEJMoa1304048.Bachert C, Mannent L, Naclerio RM, et al. Effect of subcutaneous Dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis: a randomized clinical trial. JAMA. 2016; 315(5):469–479. doi: 10.1001/jama.2015.19330.Bachert C, Mannent L, Naclerio RM, et al. Effect of subcutaneous Dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis: a randomized clinical trial. JAMA. 2016; 315(5):469–479. doi: 10.1001/jama.2015.19330.Ou Z, Chen C, Chen A, et al. Adverse events of dupilumab in adults with moderate-to-severe atopic dermatitis: a metaanalysis. Int Immunopharmacol. 2018;54:303–310. doi: 10.1016/j.intimp.2017.11.031.Ou Z, Chen C, Chen A, et al. Adverse events of dupilumab in adults with moderate-to-severe atopic dermatitis: a metaanalysis. Int Immunopharmacol. 2018;54:303–310. doi: 10.1016/j.intimp.2017.11.031.Thomson J, Wernham A, Williams HC. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a critical appraisal. Br J Dermatol. 2018;178(4):897–902. doi: 10.1111/bjd.16317.Thomson J, Wernham A, Williams HC. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a critical appraisal. Br J Dermatol. 2018;178(4):897–902. doi: 10.1111/bjd.16317.

The authors declare that there are no conflicts of interest present.