Russian Journal of AllergyRussian Journal of AllergyРоссийский Аллергологический Журнал1810-88302686-682XPublishing House ABV Press29210.36691/RJA292ArticlesСтатьиReview ArticleCURRENT CONCEPTS OF ATOPIC DERMATITIS IN CHILDREN: PROBLEMS AND PROSPECTSАКТУАЛЬНЫЙ АТОПИЧЕСКИЙ ДЕРМАТИТ: ПРОБЛЕМЫ И ПЕРСПЕКТИВЫSmirnovaG IСмирноваГалина Ивановна

профессор кафедры педиатрии педиатрического факультета, доктор медицинских наук, Заслуженный врач Российской Федерации.

gismimova@yandex.ruI.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian FederationФГАОУ ВО «Первыт Московский государственныт медицинский университет им. И.М Сеченова» Минздрава России (Сеченовский университет)15102017144-5VOL 14, NO4-5 (2017)ТОМ 14, №4-5 (2017)303910032020Copyright ©; 2017, Pharmarus Print MediaCopyright ©; 2017, Фармарус Принт Медиа2017Pharmarus Print MediaФармарус Принт Медиаhttps://rusalljournal.ru/raj/article/view/292

Modern data describing the current understanding of the pathogenesis of atopic dermatitis (AD): a genetic predisposition to atopy, disturbances of the intestinal microbiome, disruptions of epidermal barrier integrity and a cascade of immune responses, contributing allergic inflammation in the skin are presented. There are both described several mechanisms of acute and chronic phases of AD, the main directions of pathogenetically substantiated treatment of AD in children and indicated the prospects of new preparations specific blockers of proinflammatory cytokines involved in the development of AD - crisaborole, dupilumab, apremilast et al. External therapy of atopic skin lesions in AD children with modern dermatological cosmetics is presented.

Представлена современная концепция формирования атопического дерматита (АтД), которая рассматривается как комплекс факторов, включающих генетическую предрасположенность к атопии, нарушения кишечного микробиома, изменения целостности эпидермального барьера и каскад клеточных и иммунных реакций, реализующих аллергическое воспаление в коже. Описаны механизмы формирования АтД, основные направления патогенетически обоснованного лечения АтД и указаны перспективы использования новых биологических препаратов - специфических блокаторов провоспалительных цитокинов, вовлеченных в патогенез болезни, таких как кризаборол, дупилумаб, апремиласт и др. Детально представлен собственный опыт наружного лечения атопических повреждений кожи с использованием средств современной дерматологической косметики.

reviewpathogenesis of atopic dermatitis in childrenthe skins barrier function, phases of ADfeatures of topical treatment of atopic dermatitispharmacotherapy of ADspecific blockers of proinflammatory cytokinesmodern means of dermatological cosmeticsобзорпатогенез атопического дерматитадиагностика атопического дерматитафазы течениянаружная тераоия атопического дерматитафармакотерапияспецифические блокаторы цитокиновсовременные средства дерматологической косметикиAbuabara K, Margolis DJ, Langan SM. The Long-Term Course of Atopic Dermatitis. Dermatol Clin. 2017;35:291-297. DOI: 10.1016/j.det.2017.02.003.Drucker AM, Wang AR, Li WQ, Sevetson E, Block JK, Qureshi AA. The Burden of Atopic Dermatitis: Summary of a Report for the National Eczema Association. J Invest Dermatol. 2017;137:26-30. DOI: 10.1016/j.jid.2016.07.012.Silverberg JI. Public Health Burden and Epidemiology of Atopic Dermatitis. Dermatol Clin. 2017;35:283-289. DOI: 10.1016/j. det.2017.02.002.Narla S, Hsu DY, Thyssen JP, Silverberg JI. Inpatient financial burden of atopic dermatitis in the United States. J Invest Dermatol. 2017;(17):22-202. DOI: 10.1016/j.jid.2017.02.975.Sach TH, McManus E, Mcmonagle C, Levell N. Economic evidence for the prevention and treatment of atopic eczema: a protocol for a systematic review. Syst Rev. 2016;5:90. DOI: 10.1186/s13643-016-0262-0.Filanovsky MG, Pootongkam S, Tamburro JE, Smith MC, Ganocy SJ, Nedorost ST. The Financial and Emotional Impact of Atopic Dermatitis on Children and Their Families. J Pediatr. 2016;169:284-90.e5. DOI: 10.1016/j.jpeds.2015.10.077.Qiao M, Xiao D, Qian L, Qiao J. The Natural Course of Atopic Dermatitis and the Association with Asthma. Inflammation. 2017;40:546-554. DOI: 10.1007/s10753-016-0501-5.Bieber T. How to Define Atopic Dermatitis? Dermatol Clin. 2017;35:275-281. DOI: 10.1016/j.det.2017.02.001.Sidbury R, Khorsand K. Evolving Concepts in Atopic Dermatitis. Curr Allergy Asthma Rep. 2017;17:42. DOI: 10.1007/s11882-017-0710-5.Kim JE, Kim JS, Cho DH, Park HJ. Molecular Mechanisms of Cutaneous Inflammatory Disorder: Atopic Dermatitis. Int J Mol Sci. 2016;17. pii: E1234. DOI: 10.3390/ijms17081234.Смирнова Г.И. Управление течением болезни: атопический дерматит у детей. Российский педиатрический журнал. 2014;(17):45-53Malik K, Heitmiller KD, Czarnowicki T. An Update on the Pathophysiology ofAtopic Dermatitis. Dermatol Clin. 2017;35:317-326. DOI: 10.1016/j.det.2017.02.006.Kabashima K. New concept of the pathogenesis of atopic dermatitis: Interplay among the barrier, allergy, and pruritus as a trinity. J Dermatol Sci. 2013;13:923-1811.Anbunathan H, Bowcock AM. The Molecular Revolution in Cutaneous Biology: The Era of Genome-Wide Association Studies and Statistical, Big Data, and Computational Topics. J Invest Dermatol. 2017; 137:113-118. DOI: 10.1016/j.jid.2016.03.047.Brown SJ. Molecular mechanisms in atopic eczema: insights gained from genetic studies. J Pathol. 2017;241:140-145. DOI: 10.1002/path.4810.Totsuka A, Omori-Miyake M, Kawashima M, Yagi J, Tsunemi Y. Expression of keratin 1, keratin 10, desmoglein 1 and desmocollin 1 in the epidermis: possible downregulation by interleukin-4 and interleukin-13 in atopic dermatitis. Eur J Dermatol. 2017. DOI: 10.1684/ejd.2017.2985.Mu Z, Zhao Y, Liu X, Chang C, Zhang J. Molecular biology of atopic dermatitis. Clin Rev Allergy Immunol. 2014;47:193-218. DOI: 10.1007/s12016-014-8415-1.Letourneau NL, Kozyrskyj AL, Cosic N, Ntanda HN, Anis L, Hart MJ, Campbell TS, Giesbrecht GF. Maternal sensitivity and social support protect against childhood atopic dermatitis. Allergy Asthma Clin Immunol. 2017;13:26. DOI: 10.1186/s13223-017-0199-4.Vaughn AR, Tannhauser P, Sivamani RK, Shi VY. Mother Nature in Eczema: Maternal Factors Influencing Atopic Dermatitis. Pediatr Dermatol. 2017;34:240-246. DOI: 10.1111/pde.13149.Смирнова Г.И., Манкуте Г.Р Микробиота кишечника и атопический дерматит у детей. Российский педиатрический журнал. 2015;(18):4653Wollina U. Microbiome in atopic dermatitis. Clin Cosmet Investig Dermatol. 2017;10:51-56. DOI: 10.2147/CCID.S130013.Clausen ML, Edslev SM, Andersen PS, Clemmensen K, Krogfelt KA, Agner T. Staphylococcus aureus colonization in atopic eczema and its association with filaggrin gene mutations. Br J Dermatol. 2017. DOI: 10.1111/bjd.15470.Hon KL, Tsang KY, Kung JS, Leung TF, Lam CW, Wong CK. Clinical Signs, Staphylococcus and Atopic Eczema-Related Seromarkers. Molecules. 2017;22:291. DOI: 10.3390/molecules22020291.Heimall J, Spergel JM. Filaggrin mutations and atopy: consequences for future therapeutics. Expert Rev Clin Immunol. 2012;8:189-197. DOI: 10.1586/eci.11.100.McAleer MA, Irvine AD. The multifunctional role of filaggrin in allergic skin disease. J Allergy Clin Immunol. 2013;131:280-291. DOI: 10.1016/j.jaci.2012.12.668.Wang XW, Wang JJ, Gutowska-Owsiak D, Salimi M, Selvakumar TA, Gwela A, Chen LY, Wang YJ, Giannoulatou E, Ogg G. Deficiency of filaggrin regulates endogenous cysteine protease activity, leading to impaired skin barrier function. Clin Exp Dermatol. 2017. DOI: 10.1111/ced.13113.Takahashi T, Gallo RL. The Critical and Multifunctional Roles of Antimicrobial Peptides in Dermatology. Dermatol Clin. 2017;35:39-50. DOI: 10.1016/j.det.2016.07.006.Sun D, Ong PY. Infectious Complications in Atopic Dermatitis. Immunol Allergy Clin North Am. 2017;37:75-93. DOI: 10.1016/j. iac.2016.08.015.Смирнова Г.И. Атопический дерматит и инфекции кожи у детей. Российский педиатрический журнал. 2014;(17):49-56Lipinska-Opalka A, Wawrzyniak A, Lewicki S, Zdanowski R, Kalicki B. Evaluation of Immune Indices and Serum Vitamin D Content in Children with Atopic Dermatitis. Adv Exp Med Biol. 2017. DOI: 10.1007/5584_2017_20.Wang SS, Hon KL, Kong AP, Pong HN, Wong GW, Leung TF. Vitamin D deficiency is associated with diagnosis and severity of childhood atopic dermatitis. Pediatr Allergy Immunol. 2014;25:30-5. DOI: 10.1111/pai.12167.Kasraie S, Werfel T. Role of macrophages in the pathogenesis of atopic dermatitis. Mediators Inflamm. 2013;942375. DOI: 10.1155/2013/942375.Wallmeyer L, Dietert K, Sochorová M, Gruber AD, Kleuser B, Vâvrovâ K, Hedtrich S. TSLP is a direct trigger for T-cell migration in filaggrin-deficient skin equivalents. Sci Rep. 2017;7:774. DOI: 10.1038/s41598-017-00670-2.Смирнова Г.И. Современные принципы диагностики и лечения осложненных форм атопического дерматита у детей. Российский педиатрический журнал. 2010;5:3743Furue M, Chiba T, Tsuji G, Ulzii D, Kido-Nakahara M, Nakahara T, Kadono T. Atopic dermatitis: immune deviation, barrier dysfunction, IgE autoreactivity and new therapies. Allergol Int. 2017;16:1323-8930. DOI: 10.1016/j.alit.2016.12.002.Berker M, Frank LJ, Geßner AL, Grassl N, Holtermann AV, Höppner S et al. Allergies - A T-cells perspective in the era beyond the TH1/TH2 paradigm. Clin Immunol. 2017;174:73-83. DOI: 10.1016/j.clim.2016.11.001.Silverberg JI, Kantor R. The Role of Interleukins 4 and/or 13 in the Pathophysiology and Treatment of Atopic Dermatitis. Dermatol Clin. 2017;35:327-334. DOI: 10.1016/j.det.2017.02.005.Gandhi NA, Pirozzi G, Graham NMH. Commonality of the IL-4/IL-13 pathway in atopic diseases. Expert Rev Clin Immunol. 2017;13:425-437. DOI: 10.1080/1744666X.2017.1298443.Eyerich K, Novak N. Immunology of atopic eczema: overcoming the Th1/Th2 paradigm. Allergy. 2013;68:974-82. DOI: 10.1111/ all.12184.Jiang Y, Ma W. Assessment of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Atopic Dermatitis Patients. Med Sci Monit. 2017;23:1340-1346.Lou H, Lu J, Choi EB, Oh MH, Jeong M, Barmettler S et al. Expression of IL-22 in the Skin Causes Th2-Biased Immunity, Epidermal Barrier Dysfunction, and Pruritus via Stimulating Epithelial Th2 Cytokines and the GRP Pathway. J Immunol. 2017;198:2543-2555. DOI: 10.4049/jimmunol.1600126.Nadif R, Zerimech F, Bouzigon E, Matran R. The role of eosinophils and basophils in allergic diseases considering genetic findings. Curr Opin Allergy Clin Immunol. 2013;13:507-513. DOI: 10.1097/ACI.0b013e328364e9c0.Orfali RL, Zaniboni MC, Aoki V. Profile of skin barrier proteins and cytokines in adults with atopic dermatitis. G Ital Dermatol Venereol. 2017;152:140-147. DOI: 10.23736/S0392-0488.16.05533-4.Shiraishi H, Masuoka M, Ohta S, Suzuki S, Arima K, Taniguchi K, Aoki S, Toda S, Yoshimoto T, Inagaki N, Conway SJ, Narisawa Y, Izuhara K. Periostin contributes to the pathogenesis of atopic dermatitis by inducing TSLP production from keratinocytes. Allergol Int. 2012;61:563-72. DOI: 10.2332/allergolint.10-OA-0297.Heo WI, Park KY, Jin T, Lee MK, Kim M, Choi EH, Kim HS, Bae JM, Moon NJ, Seo SJ. Identification of novel candidate variants including COL6A6 polymorphisms in early-onset atopic dermatitis using whole-exome sequencing. BMC Med Genet. 2017;18:8. DOI: 10.1186/s12881-017-0368-9.Elias MS, Long HA, Newman CF, Wilson PA, West A, McGill PJ, Wu KC, Donaldson MJ, Reynolds NJ. Proteomic analysis of filaggrin deficiency identifies molecular signatures characteristic of atopic eczema. J Allergy Clin Immunol. 2017;17:91-6749. DOI: 10.1016/j.jaci.2017.01.039.Eto H, Tsuji G, Chiba T, Furue M, Hyodo F. Non-invasive evaluation of atopic dermatitis based on redox status using in vivo dynamic nuclear polarization magnetic resonance imaging. Free Radic Biol Med. 2017;103:209-215. DOI: 10.1016/j.freerad-biomed.2016.12.043.Frings VG, Böer-Auer A, Breuer K. Histomorphology and Immunophenotype of Eczematous Skin Lesions Revisited-Skin Biopsies Are Not Reliable in Differentiating Allergic Contact Dermatitis, Irritant Contact Dermatitis, and Atopic Dermatitis. Am J Dermatopathol. 2017. DOI: 10.1097/DAD.0000000000000842.Silverberg NB, Durán-McKinster C. Special Considerations for Therapy of Pediatric Atopic Dermatitis. Dermatol Clin. 2017;35:351-363. DOI: 10.1016/j.det.2017.02.008.Roduit C, Frei R, Depner M, Karvonen AM, Renz H, Braun-Fahrländer C et al. Phenotypes of Atopic Dermatitis Depending on the Timing of Onset and Progression in Childhood. JAMA Pediatr. 2017. DOI: 10.1001/jamapediatrics.2017.0556.Cabanillas B, Brehler AC, Novak N. Atopic dermatitis phenotypes and the need for personalized medicine. Curr Opin Allergy Clin Immunol. 2017. DOI: 10.1097/ACI.0000000000000376.Ginsberg DN, Eichenfield LF. Debates in allergy medicine: Specific immunotherapy in children with atopic dermatitis, the «con» view. World Allergy Organ J. 2016;9:16. DOI: 10.1186/ s40413-016-0107-2.Смирнова Г.И. Эффективное лечение атопического дерматита у детей. Российский педиатрический журнал. 2012;(5):2330 [Smirnova GI. effectivnoue lechenie atopicheskogo dermatita u detei. Rossiyskiy pediatricheskiy zhurnal. 2012;(5):2330 (in Russ.)].LeBovidge JS, Elverson W, Timmons KG, Hawryluk EB, Rea C, Lee M et al. Multidisciplinary interventions in the management of atopic dermatitis. J Allergy Clin Immunol. 2016;138:325-34. DOI: 10.1016/j.jaci.2016.04.003.Damm JA, Smith B, Greisen G, Krogfelt KA, Clausen ML, Agner T. The influence of probiotics for preterm neonates on the incidence of atopic dermatitis-results from a historically controlled cohort study. Arch Dermatol Res. 2017;309:259-264. DOI: 10.1007/s00403-017-1725-4.Ouwehand AC. A review of dose-responses of probiotics in human studies. Benef Microbes. 2017;8:143-151. DOI: 10.3920/ BM2016.0140.Siegfried EC, Jaworski JC, Kaiser JD, Hebert AA. Systematic review of published trials: long-term safety of topical corticosteroids and topical calcineurin inhibitors in pediatric patients with atopic dermatitis. BMC Pediatr. 2016;16:75. DOI: 10.1186/s12887-016-0607-9.Смирнова Г.И. Наружная терапия атопического дерматита у детей - дифференцированный подход. Российский Аллергологический Журнал. 2012;(5):4654Lauffer F, Ring J. Target-oriented therapy: Emerging drugs for atopic dermatitis. Expert Opin Emerg Drugs. 2016;21:81-9. DOI: 10.1517/14728214.2016.1146681.Tom WL, Van Syoc M, Chanda S, Zane LT. Pharmacokinetic Profile, Safety, and Tolerability of Crisaborole Topical Ointment, 2% in Adolescents with Atopic Dermatitis: An Open-Label Phase 2a Study. Pediatr Dermatol. 2016;33:150-9. DOI: 10.1111/ pde.12780.Kraft M, Worm M. Dupilumab in the treatment of moderate-to-severe atopic dermatitis. Expert Rev Clin Immunol. 2017;13:301-310. DOI: 10.1080/1744666X.2017.1292134.Saporito RC, Cohen DJ. Apremilast Use for Moderate-to-Severe Atopic Dermatitis in Pediatric Patients. Case Rep Dermatol. 2016;8:179-184. DOI: 10.1159/000446836.Van Zuuren Ej, Fedorowicz Z, Christensen R, Lavrijsen A, Arents BWM. Emollients and moisturisers for eczema. Cochrane Database Syst Rev. 2017;2:CD012119. DOI: 10.1002/14651858. CD012119.pub2.Bodemer C, Guillet G, Cambazard F, Boralevi F, Ballarini S, Milliet C et al. Adjuvant treatment with the bacterial lysate (OM-85) improves management of atopic dermatitis: A randomized study. PLoS One. 2017;12:e0161555. DOI: 10.1371/journal. pone.0161555.Blome C, Radtke MA, Eissing L, Augustin M. Quality of Life in Patients with Atopic Dermatitis: Disease Burden, Measurement, and Treatment Benefit. Am J Clin Dermatol. 2016;17:163-9. DOI: 10.1007/s40257-015-0171-3.Christodoulides P, Hirata Y, Domínguez-Hüttinger E, Danby SG, Cork MJ, Williams HC et al. Computational design of treatment strategies for proactive therapy on atopic dermatitis using optimal control theory. Philos Trans A Math Phys Eng Sci. 2017;375pii: 20160285. DOI: 10.1098/rsta.2016.0285.