vspВопросы современной педиатрииCurrent Pediatrics1682-55271682-5535Издательство «ПедиатрЪ»10.15690/vsp.v24i4.2931vsp-3816Research ArticleКЛИНИЧЕСКОЕ НАБЛЮДЕНИЕCLINICAL OBSERVATIONSПрименение дупилумаба у пациента с тяжелым эозинофильным эзофагитом, сочетанным с Т2-ассоциированными заболеваниями: клинический случайDupilumab Administration in the Patient with Severe Eosinophilic Esophagitis Combined with T2-Associated Diseases: Case Studyhttps://orcid.org/0000-0002-6945-1104ВязанкинаС. С.VyazankinaSvetlana S.

Вязанкина Светлана Святославовна, младший научный сотрудник лаборатории клинической иммунологии и нутрициологии, врач аллергологиммунолог отделения дерматологии и аллергологии НИИ детской дерматологии

119991, Москва, Ломоносовский пр-т, д. 2/62, стр. 1

Moscow

svsvpav@mail.ruhttps://orcid.org/0000-0003-2252-8570МурашкинН. Н.MurashkinNikolay N.

Москва

Moscow

https://orcid.org/0000-0002-3056-403XМакароваС. Г.MakarovaSvetlana G.

Москва

Moscow

https://orcid.org/0000-0002-8305-7592ЛохматовМ. М.LokhmatovMaksim M.

Москва

Moscow

https://orcid.org/0000-0002-7379-7298БудкинаТ. Н.BudkinaTatyana N.

Москва

Moscow

https://orcid.org/0000-0001-5739-0941ЛеоноваМ. А.LeonovaMariya A.

Москва

Moscow

https://orcid.org/0000-0002-6034-8231МатерикинА. И.MaterikinAleksandr I.

Москва

Moscow

https://orcid.org/0000-0002-1650-652XЕрешкоО. А.EreshkoOksana A.

Москва

Moscow

https://orcid.org/0000-0002-1107-8693КуликовК. А.KulikovKirill A.

Москва

Moscow

Национальный медицинский исследовательский центр здоровья детейРоссияNational Medical Research Center of Children’s HealthRussian FederationНациональный медицинский исследовательский центр здоровья детей; Первый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский Университет); Центральная государственная медицинская академияРоссияNational Medical Research Center of Children’s Health; Sechenov First Moscow State Medical University; Central State Medical Academy of Department of Presidential AffairsRussian FederationНациональный медицинский исследовательский центр здоровья детей; Первый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский Университет)РоссияNational Medical Research Center of Children’s Health; Sechenov First Moscow State Medical UniversityRussian Federation202518092025244299304Copyright © Вязанкина С.С., Мурашкин Н.Н., Макарова С.Г., Лохматов М.М., Будкина Т.Н., Леонова М.А., Материкин А.И., Ерешко О.А., Куликов К.А., 20252025Вязанкина С.С., Мурашкин Н.Н., Макарова С.Г., Лохматов М.М., Будкина Т.Н., Леонова М.А., Материкин А.И., Ерешко О.А., Куликов К.А.Vyazankina S.S., Murashkin N.N., Makarova S.G., Lokhmatov M.M., Budkina T.N., Leonova M.A., Materikin A.I., Ereshko O.A., Kulikov K.A.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/3816

Обоснование. Т2-ассоциированные заболевания, включая эозинофильный эзофагит (ЭоЭ), атопический дерматит и бронхиальную астму, объединены общим патогенетическим механизмом — гиперпродукцией интерлейкинов (IL) 4, 5 и 13. Стандартная терапия при тяжелых формах ЭоЭ, а также при коморбидных Т2-патологиях может быть неэффективной. Дупилумаб, моноклональное антитело к рецептору IL-4R, селективно блокирует сигнальные пути IL-4/IL-13. В этой связи препарат может быть рассмотрен в качестве перспективного варианта терапии ЭоЭ с рефрактерным течением и множественными атопическими состояниями. Описание клинического случая. Ребенку с ЭоЭ, осложненным стенозом пищевода на фоне неэффективной стандартной терапии (ингибиторы протонной помпы в сочетании с топическими кортикостероидами и элиминационной диетой), коморбидным с атопическим дерматитом и аллергическим ринитом, назначен дупилумаб по схеме 300 мг каждые 2 нед (при массе тела ребенка 34 кг суммарная дозировка составила 800 г). Через 3 мес после инициации биологической терапии отмечено купирование симптомов дисфагии и болей в животе. Пациент начал есть твердую пищу, улучшился аппетит. Отмечена нормализация показателей физического развития (HAZ, BAZ). На фоне проводимой терапии удалось достичь ремиссии атопического дерматита и избежать инвазивной эндоскопической дилатации пищевода. Побочные эффекты при применении дупилумаба не зарегистрированы. Заключение. Дупилумаб значимо уменьшает эозинофильную инфильтрацию слизистой оболочки пищевода и выраженность симптомов у пациента с тяжелым ЭоЭ, коморбидным с Т2-ассоциированными заболеваниями. Оказывая модулирующее действие на генетически обусловленное Т2-воспаление, препарат открывает новые возможности персонализированной терапии пациентов с ЭоЭ.

Background. T2-associated diseases such as eosinophilic esophagitis (EoE), atopic dermatitis, and bronchial asthma have common pathogenetic mechanism — hyperproduction of interleukins (IL) 4, 5 and 13. Standard therapy for severe forms of EoE and comorbid T2 pathologies may be ineffective. Dupilumab (monoclonal antibody to the IL-4R receptor) selectively blocks IL-4/IL-13 signaling pathways. Thus, this medication can be considered as the promising treatment option for EoE with refractory course and multiple atopic conditions. Case description. Child with EoE complicated by esophageal stenosis, comorbid atopic dermatitis, and allergic rhinitis, with ineffective standard therapy (proton pump inhibitors, topical corticosteroids, and elimination diet), was prescribed dupilumab, 300 mg every 2 weeks (child’s weight of 34 kg, total dosage was 800 g). Dysphagia and abdominal pains resolved 3 months after biological therapy onset. The patient has started eating solid food, his appetite has improved. Normalization of physical development indicators (HAZ, BAZ) was noted. Remission of atopic dermatitis was achieved during the therapy, and endoscopic esophageal dilation was avoided. No side effects were reported due to dupilumab therapy. Conclusion. Dupilumab significantly reduces eosinophilic infiltration of esophageal mucosa and symptoms severity in the patient with severe EoE combined with T2-associated diseases. This medication opens new possibilities for personalized therapy of patients with EoE via modulating effect on genetically determined T2-inflammation.

эозинофильный эзофагитдетистеноз пищеводадупилумабТ2-воспалениеeosinophilic esophagitischildrenesophageal stenosisdupilumabТ2-inflammationОтсутствует.Not specified.ReferencesAmil-Dias J, Oliva S, Papadopoulou A, et al. Diagnosis and management of eosinophilic esophagitis in children: An update from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr. 2024;79(2):394–437. doi: https://doi.org/10.1002/jpn3.12188Amil-Dias J, Oliva S, Papadopoulou A, et al. Diagnosis and management of eosinophilic esophagitis in children: An update from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr. 2024;79(2):394–437. doi: https://doi.org/10.1002/jpn3.12188Эозинофильный эзофагит: клинические рекомендации. — 2024. Доступно по: https://www.pediatr-russia.ru/information/klinrek/proekty-klinicheskikh-rekomendatsiy/Клин_рекомендации_ЭозЭ_27.02.24.pdf. Ссылка активна на 19.07.2025.Eozinofil’nyi ezofagit: Clinical guidelines. 2024. (In Russ). Доступно по: https://www.pediatr-russia.ru/information/klinrek/proekty-klinicheskikh-rekomendatsiy/Клин_рекомендации_ЭозЭ_27.02.24.pdf. Ссылка активна на 19.07.2025.Vinit C, Dieme A, Courbage S, et al. Eosinophilic esophagitis: Pathophysiology, diagnosis, and management. Arch Pediatr. 2019;26(3):182–190. doi: https://doi.org/10.1016/j.arcped.2019.02.005Vinit C, Dieme A, Courbage S, et al. Eosinophilic esophagitis: Pathophysiology, diagnosis, and management. Arch Pediatr. 2019;26(3):182–190. doi: https://doi.org/10.1016/j.arcped. 2019.02.005Simon D, Page B, Vogel M, et al. Evidence of an abnormal epithelial barrier in active, untreated and corticosteroid-treated eosinophilic esophagitis. Allergy. 2018;73(1):239–247. doi: https://doi.org/10.1111/all.13244Simon D, Page B, Vogel M, et al. Evidence of an abnormal epithelial barrier in active, untreated and corticosteroid-treated eosinophilic esophagitis. Allergy. 2018;73(1):239–247. doi: https://doi.org/10.1111/all.13244Ruffner MA, Cianferoni A. Phenotypes and endotypes in eosinophilic esophagitis. Ann Allergy Asthma Immunol. 2020;124(3):233–239. doi: https://doi.org/10.1016/j.anai.2019.12.011Ruffner MA, Cianferoni A. Phenotypes and endotypes in eosinophilic esophagitis. Ann Allergy Asthma Immunol. 2020;124(3):233–239. doi: https://doi.org/10.1016/j.anai.2019.12.011Blanchard C, Wang N, Stringer KF, et al. Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis. J Clin Invest. 2006;116(2):536–547. doi: https://doi.org/10.1172/JCI26679Blanchard C, Wang N, Stringer KF, et al. Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis. J Clin Invest. 2006;116(2):536–547. doi: https://doi.org/10.1172/JCI26679Oliva S, Dias JA, Rea F, et al. Characterization of Eosinophilic Esophagitis From the European Pediatric Eosinophilic Esophagitis Registry (pEEr) of ESPGHAN. J Pediatr Gastroenterol Nutr. 2022;75(3):325–333. doi: https://doi.org/10.1097/MPG.0000000000003530Oliva S, Dias JA, Rea F, et al. Characterization of Eosinophilic Esophagitis From the European Pediatric Eosinophilic Esophagitis Registry (pEEr) of ESPGHAN. J Pediatr Gastroenterol Nutr. 2022;75(3):325–333. doi: https://doi.org/10.1097/MPG.0000000000003530Warners MJ, Oude Nijhuis RAB, de Wijkerslooth LRH, et al. The natural course of eosinophilic esophagitis and long-term consequences of undiagnosed disease in a large cohort. Am J Gastroenterol. 2018;113(6):836–844. doi: https://doi.org/10.1038/s41395-018-0052-5Warners MJ, Oude Nijhuis RAB, de Wijkerslooth LRH, et al. The natural course of eosinophilic esophagitis and long-term consequences of undiagnosed disease in a large cohort. Am J Gastroenterol. 2018;113(6):836–844. doi: https://doi.org/10.1038/s41395-018-0052-5Kim JP, Weingart G, Hiramoto B, et al. Clinical outcomes of adults with eosinophilic esophagitis with severe stricture. Gastrointest Endosc. 2020;92(1):44–53. doi: https://doi.org/10.1016/j.gie.2020.01.015Kim JP, Weingart G, Hiramoto B, et al. Clinical outcomes of adults with eosinophilic esophagitis with severe stricture. Gastrointest Endosc. 2020;92(1):44–53. doi: https://doi.org/10.1016/j.gie.2020.01.015Schoepfer AM, Safroneeva E, Bussmann C, et al. Delay in diagnosis of eosinophilic esophagitis increases risk for stricture formation in a time-dependent manner. Gastroenterology. 2013;145(6):1230–1236.e62. doi: https://doi.org/10.1053/j.gastro.2013.08.015Schoepfer AM, Safroneeva E, Bussmann C, et al. Delay in diagnosis of eosinophilic esophagitis increases risk for stricture formation in a time-dependent manner. Gastroenterology. 2013;145(6):1230–1236.e62. doi: https://doi.org/10.1053/j.gastro.2013.08.015Papadopoulou A, Koletzko S, Heuschkel R, et al. Management guidelines of eosinophilic esophagitis in childhood. J Pediatr Gastroenterol Nutr. 2014;58(1):107–118. doi: https://doi.org/10.1097/MPG.0b013e3182a80be1Papadopoulou A, Koletzko S, Heuschkel R, et al. Management guidelines of eosinophilic esophagitis in childhood. J Pediatr Gastroenterol Nutr. 2014;58(1):107–118. doi: https://doi.org/10.1097/MPG.0b013e3182a80be1Dellon ES, Woosley JT, Arrington A, et al. Rapid Recurrence of Eosinophilic Esophagitis Activity After Successful Treatment in the Observation Phase of a Randomized, Double-Blind, Double-Dummy Trial. Clin Gastroenterol Hepatol. 2020;18(7):1483–1492.e2. doi: https://doi.org/10.1016/j.cgh.2019.08.050Dellon ES, Woosley JT, Arrington A, et al. Rapid Recurrence of Eosinophilic Esophagitis Activity After Successful Treatment in the Observation Phase of a Randomized, Double-Blind, Double-Dummy Trial. Clin Gastroenterol Hepatol. 2020;18(7):1483–1492.e2. doi: https://doi.org/10.1016/j.cgh.2019.08.050Chang NC, Thakkar KP, Ketchem CJ, et al. A Gap in Care Leads to Progression of Fibrosis in Eosinophilic Esophagitis Patients. Clin Gastroenterol Hepatol. 2022;20(8):1701–1708.e2. doi: https://doi.org/10.1016/j.cgh.2021.10.028Chang NC, Thakkar KP, Ketchem CJ, et al. A Gap in Care Leads to Progression of Fibrosis in Eosinophilic Esophagitis Patients. Clin Gastroenterol Hepatol. 2022;20(8):1701–1708.e2. doi: https://doi.org/10.1016/j.cgh.2021.10.028Lucendo AJ, Molina-Infante J, Arias Á, et al. Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults. United European Gastroenterol J. 2017;5(3):335–358. doi: https://doi.org/10.1177/2050640616689525Lucendo AJ, Molina-Infante J, Arias Á, et al. Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults. United European Gastroenterol J. 2017;5(3):335–358. doi: https://doi.org/10.1177/2050640616689525Chehade M, Dellon ES, Spergel JM, et al. Dupilumab for Eosinophilic Esophagitis in Patients 1 to 11 Years of Age. N Engl J Med. 2024;390(24):2239–2251. doi: https://doi.org/10.1056/NEJMoa2312282Chehade M, Dellon ES, Spergel JM, et al. Dupilumab for Eosinophilic Esophagitis in Patients 1 to 11 Years of Age. N Engl J Med. 2024;390(24):2239–2251. doi: https://doi.org/10.1056/NEJMoa2312282Patel SA. Real-world efficacy of dupilumab in four cases of paediatric-onset fibrostenotic eosinophilic esophagitis. Clin Exp Pharmacol Physiol. 2024;51(8):e13903. doi: https://doi.org/10.1111/1440-1681.13903Patel SA. Real-world efficacy of dupilumab in four cases of paediatric-onset fibrostenotic eosinophilic esophagitis. Clin Exp Pharmacol Physiol. 2024;51(8):e13903. doi: https://doi.org/10.1111/1440-1681.13903Gangadharan Nambiar G, Rahhal R, Davis BP, et al. Refractory Pediatric Fibrostenotic Eosinophilic Esophagitis Treated With Dupilumab. ACG Case Rep J. 2022;9(11):e00887. doi: https://doi.org/10.14309/crj.0000000000000887Gangadharan Nambiar G, Rahhal R, Davis BP, et al. Refractory Pediatric Fibrostenotic Eosinophilic Esophagitis Treated With Dupilumab. ACG Case Rep J. 2022;9(11):e00887. doi: https://doi.org/10.14309/crj.0000000000000887Hudgens S, Evans C, Phillips E, Hill M. Psychometric validation of the Dysphagia Symptom Questionnaire in patients with eosinophilic esophagitis treated with budesonide oral suspension. J Patient Rep Outcomes. 2017;1(1):3. doi: https://doi.org/10.1186/s41687-017-0006-5Hudgens S, Evans C, Phillips E, Hill M. Psychometric validation of the Dysphagia Symptom Questionnaire in patients with eosinophilic esophagitis treated with budesonide oral suspension. J Patient Rep Outcomes. 2017;1(1):3. doi: https://doi.org/10.1186/s41687-017-0006-5Ghezzi M, Pozzi E, Abbattista L, et al. Barrier Impairment and Type 2 Inflammation in Allergic Diseases: The Pediatric Perspective. Children (Basel). 2021;8(12):1165. doi: https://doi.org/10.3390/children8121165Ghezzi M, Pozzi E, Abbattista L, et al. Barrier Impairment and Type 2 Inflammation in Allergic Diseases: The Pediatric Perspective. Children (Basel). 2021;8(12):1165. doi: https://doi.org/10.3390/children8121165Meng J, Xiao H, Xu F, et al. Systemic barrier dysfunction in type 2 inflammation diseases: perspective in the skin, airways, and gastrointestinal tract. Immunol Res. 2025;73(1):60. doi: https://doi.org/10.1007/s12026-025-09606-9Meng J, Xiao H, Xu F, et al. Systemic barrier dysfunction in type 2 inflammation diseases: perspective in the skin, airways, and gastrointestinal tract. Immunol Res. 2025;73(1):60. doi: https://doi.org/10.1007/s12026-025-09606-9Munoz-Persy M, Lucendo AJ. Treatment of eosinophilic esophagitis in the pediatric patient: an evidence-based approach. Eur J Pediatr. 2018;177(5):649–663. doi: https://doi.org/10.1007/s00431-018-3129-7Munoz-Persy M, Lucendo AJ. Treatment of eosinophilic esophagitis in the pediatric patient: an evidence-based approach. Eur J Pediatr. 2018;177(5):649–663. doi: https://doi.org/10.1007/s00431-018-3129-7Philpott H, Dellon ES. The role of maintenance therapy in eosinophilic esophagitis: who, why, and how? J Gastroenterol. 2018;53(2): 165–171. doi: https://doi.org/10.1007/s00535-017-1397-zPhilpott H, Dellon ES. The role of maintenance therapy in eosinophilic esophagitis: who, why, and how? J Gastroenterol. 2018;53(2): 165–171. doi: https://doi.org/10.1007/s00535-017-1397-zAlexander R, Kassmeyer B, Lennon R, et al. EoE Recurrence on PPI Maintenance Therapy: You Do Not Know if You Do Not Look! Dig Dis Sci. 2024;69(11):4048–4052. doi: https://doi.org/10.1007/s10620-024-08676-3Alexander R, Kassmeyer B, Lennon R, et al. EoE Recurrence on PPI Maintenance Therapy: You Do Not Know if You Do Not Look! Dig Dis Sci. 2024;69(11):4048–4052. doi: https://doi.org/10.1007/s10620-024-08676-3Thel HL, Borinsky SA, LaFata SS, et al. Histologic Response or Endoscopic Normalization After Initial Treatment for Eosinophilic Esophagitis in Children Leads to Less Fibrostenosis over Long-Term Follow-Up. Dig Dis Sci. 2025;70(4):1428–1434. doi: https://doi.org/10.1007/s10620-025-08914-2Thel HL, Borinsky SA, LaFata SS, et al. Histologic Response or Endoscopic Normalization After Initial Treatment for Eosinophilic Esophagitis in Children Leads to Less Fibrostenosis over Long-Term Follow-Up. Dig Dis Sci. 2025;70(4):1428–1434. doi: https://doi.org/10.1007/s10620-025-08914-2García-Compeán D, González-Moreno EI, González-González JA, et al. Lack of compliance with consensus recommendations on the diagnosis of eosinophilic esophagitis (EoE) in published prevalence studies. A clinical and systematic review. J Dig Dis. 2016;17(10):660–669. doi: https://doi.org/10.1111/1751-2980.12400García-Compeán D, González-Moreno EI, GonzálezGonzález JA, et al. Lack of compliance with consensus recommendations on the diagnosis of eosinophilic esophagitis (EoE) in published prevalence studies. A clinical and systematic review. J Dig Dis. 2016;17(10):660–669. doi: https://doi.org/10.1111/1751-2980.12400Mongkonsritragoon W, Varre A, Beydoun S, et al. Factors associated with treatment response in eosinophilic esophagitis patients: Experience from a pediatric tertiary care center. Allergy Asthma Proc. 2025;46(2):135–143. doi: https://doi.org/10.2500/aap.2025.46.2401Mongkonsritragoon W, Varre A, Beydoun S, et al. Factors associated with treatment response in eosinophilic esophagitis patients: Experience from a pediatric tertiary care center. Allergy Asthma Proc. 2025;46(2):135–143. doi: https://doi.org/10.2500/aap.2025.46.2401Bredenoord AJ, Dellon ES, Schlag C, et al. Dupilumab is efficacious for eosinophilic esophagitis irrespective of prior swallowed budesonide or fluticasone, or prior treatments used alongside swallowed topical corticosteroids: results from the phase 3, randomized, placebo-controlled, LIBERTY EoE TREET trial. Expert Rev Gastroenterol Hepatol. 2025;19(2):197–209. doi: https://doi.org/10.1080/17474124.2025.2461516Bredenoord AJ, Dellon ES, Schlag C, et al. Dupilumab is efficacious for eosinophilic esophagitis irrespective of prior swallowed budesonide or fluticasone, or prior treatments used alongside swallowed topical corticosteroids: results from the phase 3, randomized, placebo-controlled, LIBERTY EoE TREET trial. Expert Rev Gastroenterol Hepatol. 2025;19(2):197–209. doi: https://doi.org/10.1080/17474124.2025.2461516Tomás-Pérez M, Domenech-Witek J, Ávila-Castellano MR, et al. Position Paper on the Treatment of Eosinophilic Esophagitis With Dupilumab. J Investig Allergol Clin Immunol. 2025;35(3):170–178. doi: https://doi.org/10.18176/jiaci.1038.Tomás-Pérez M, Domenech-Witek J, Ávila-Castellano MR, et al. Position Paper on the Treatment of Eosinophilic Esophagitis With Dupilumab. J Investig Allergol Clin Immunol. 2025;35(3):170–178. doi: https://doi.org/10.18176/jiaci.1038.

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