clinendoКлиническая эндоскопияFilin’s Clinical endoscopy2415-7813"Global Media technology" Ltd10.31146/2415-7813-endo-68-2-30-35clinendo-709Research ArticleГАСТРОЭНТЕРОЛОГИЯGASTROENTEROLOGYОпыт применения лозартана для профилактики рестенозирования пищевода у детей с дистрофической формой врожденного буллезного эпидермолизаExperience of using losartan for prevention of esophageal restenosis in children with dystrophic congenital epidermolysis bullosahttps://orcid.org/0000-0002-8805-8164ОлдаковскийВ. И.OldakovskiyV. I.violdakovsky@yandex.ruhttps://orcid.org/0000-0002-8305-7592ЛохматовМ. М.LokhmatovM. M.noemail@neicon.ruhttps://orcid.org/0000-0003-2252-8570МурашкинН. Н.MurashkinN. N.noemail@neicon.ruhttps://orcid.org/0000-0002-8563-6002ДьяконоваЕ. Ю.DyakonovaE. Yu.noemail@neicon.ruhttps://orcid.org/0000-0003-4299-3269ТупыленкоА. В.TupylenkoA. V.noemail@neicon.ruhttps://orcid.org/0000-0002-7379-7298БудкинаТ. Н.BudkinaT. N.noemail@neicon.ruhttps://orcid.org/0000-0001-5730-3684КоролевГ. А.KorolevG. A.noemail@neicon.ruhttps://orcid.org/0009-0009-4397-997XХватоваЕ. И.KhvatovaE. I.noemail@neicon.ruФедеральное государственное автономное учреждение «Национальный медицинский исследовательский центр здоровья детей» Министерства здравоохранения Российской ФедерацииNational Medical Research Center for Children’s Health2026230420266823035Copyright © Олдаковский В.И., Лохматов М.М., Мурашкин Н.Н., Дьяконова Е.Ю., Тупыленко А.В., Будкина Т.Н., Королев Г.А., Хватова Е.И., 20262026Олдаковский В.И., Лохматов М.М., Мурашкин Н.Н., Дьяконова Е.Ю., Тупыленко А.В., Будкина Т.Н., Королев Г.А., Хватова Е.И.Oldakovskiy V.I., Lokhmatov M.M., Murashkin N.N., Dyakonova E.Y., Tupylenko A.V., Budkina T.N., Korolev G.A., Khvatova E.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://clinendo.elpub.ru/jour/article/view/709

Актуальность. Дистрофический буллезный эпидермолиз (ДБЭ) - одна из наиболее тяжелых форм врожденного буллезного эпидермолиза, характеризующаяся формированием множества хирургических осложнений, в частности, стеноза пищевода. Базовой терапевтической методикой признана баллонная дилатация (БД) под рентгеновским контролем, однако для профилактики рецидивов требуется консервативное лечение. Перспективным признано использование лозартана за счет его антифибротического действия, обусловленного подавлением активности трансформирующего фактора роста-β1 (TGF-β). Цель исследования. Оценить эффективность лозартана в профилактике рестенозирования после БД пищевода у детей с ДБЭ. Материалы и методы. В исследование включены 19 детей с ДБЭ в возрасте 2-16 лет (средний возраст 9,2 ± 3,58 года): 6 мальчиков (31,6%) и 13 девочек (68,4%). Стеноз пищевода был подтверждён рентгенологически. Всем пациентам выполнена БД пищевода. В основной группе (n=9) после БД дети получали лозартан в сочетании со стандартной местной терапией; в контрольной группе (n=10) проводилась только стандартная терапия. Длительность наблюдения составила 12 месяцев. Оценивались частота рестенозирования пищевода, выраженность нутритивной недостаточности (по шкале THINC) и тяжесть заболевания (по индексу EBDASI). Результаты. В основной группе повторная дилатация потребовалась 1 ребенку (11,1%), в контрольной - 4 детям (40%). Показатели нутритивной недостаточности и индекс тяжести болезни также оказались достоверно ниже в группе детей, получавших лозартан. Нежелательных действий препарата за время наблюдения не зарегистрировано. Выводы. В настоящем исследовании лозартан продемонстировал свою безопасность, способствовал снижению частоты рестенозирования пищевода и улучшению нутритивного статуса детей с ДБЭ после БД. Однако требуются дальнейшие исследования для подтверждения его эффективности.

Introduction: Dystrophic epidermolysis bullosa (DEB), one of the most severe forms of congenital epidermolysis bullosa, is characterized by the development of multiple surgical complications, including esophageal stenosis/stricture. Fluoroscopy-guided balloon dilation (BD) is the main therapeutic approach; however conservative treatment is required to prevent recurrence. Losartan has been proposed as a promising option because of its antifibrotic effects, potentially mediated by suppression of transforming growth factor β1 (TGF-β1) signaling. Purpose: To evaluate the effectiveness of losartan for preventing restenosis after esophageal BD in children with DEB. Materials and Methods: The study included 19 children with DEB (age 2-16 years; mean age 9.2 ± 3.58 years), 6 boys (31.6%) and 13 girls (68.4%), with X-ray confirmed esophageal stenosis. All patients underwent esophageal BD. In the treatment group (n=9), children received losartan and standard topical therapy; in the control group (n=10), only standard therapy was administered. The observation period was 12 months. Outcomes included the rate of esophageal restenosis, nutritional compromise (THINC tool), and disease severity assessed (EBDASI index). Results: Repeat dilation was required in 1 child (11.1%) in the treatment group and in 4 children (40.0%) in the control group. Nutritional compromise scores and disease severity (EBDASI) were also significantly lower in the group of children treated with losartan. No adverse drug reactions were observed. Conclusions: In this study, losartan demonstrated its safety, was associated with a lower rate of esophageal restenosis, and improved nutritional status in children with DEB after BD. Further studies are required to confirm its efficacy.

дистрофический буллезный эпидермолизстеноз пищеводабаллонная дилатациярестенозированиелозартанdystrophic epidermolysis bullosaesophageal stenosisballoon dilatationrestenosislosartanReferencesFine J.D., Bruckner-Tuderman L., Eady R.A. et al. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol. 2014 Jun;70(6):1103-26. doi: 10.1016/ j.jaad.2014.01.903.Fine J.D., Bruckner-Tuderman L., Eady R.A. et al. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol. 2014 Jun;70(6):1103-26. doi: 10.1016/ j.jaad.2014.01.903.Has C., Bauer J.W., Bodemer C. et al. Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility. Br J Dermatol. 2020 Oct;183(4):614-627. doi: 10.1111/bjd.18921.Has C., Bauer J.W., Bodemer C. et al. Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility. Br J Dermatol. 2020 Oct;183(4):614-627. doi: 10.1111/bjd.18921.Horn H.M., Tidman M.J. The clinical spectrum of dystrophic epidermolysis bullosa. Br J Dermatol. 2002 Feb;146(2):267-74. doi: 10.1046/j.1365-2133.2002.04607.x.Horn H.M., Tidman M.J. The clinical spectrum of dystrophic epidermolysis bullosa. Br J Dermatol. 2002 Feb;146(2):267-74. doi: 10.1046/j.1365-2133.2002.04607.x.Travis S.P., McGrath J.A., Turnbull A.J. et al. Oral and gastrointestinal manifestations of epidermolysis bullosa. Lancet. 1992 Dec 19-26;340(8834-8835):1505-6. doi: 10.1016/0140-6736(92)92759-9.Travis S.P., McGrath J.A., Turnbull A.J. et al. Oral and gastrointestinal manifestations of epidermolysis bullosa. Lancet. 1992 Dec 19-26;340(8834-8835):1505-6. doi: 10.1016/0140-6736(92)92759-9.Guerra-Leal J.D., Meester I., Cantu-Gonzalez J.R., Ornelas-Cortinas G., Montemayor-Martinez A., Salas-Alanis J.C. The Importance of Esophagography in Patients With Recessive Dystrophic Epidermolysis Bullosa. AJR Am J Roentgenol. 2016 Oct;207(4):778-781. doi: 10.2214/AJR.16.16115.Guerra-Leal J.D., Meester I., Cantu-Gonzalez J.R., Ornelas-Cortinas G., Montemayor-Martinez A., Salas-Alanis J.C. The Importance of Esophagography in Patients With Recessive Dystrophic Epidermolysis Bullosa. AJR Am J Roentgenol. 2016 Oct;207(4):778-781. doi: 10.2214/AJR.16.16115.Malagelada J.R., Bazzoli F., Boeckxstaens G. et al. World gastroenterology organisation global guidelines: dysphagia - global guidelines and cascades update September 2014. J Clin Gastroenterol. 2015 May-Jun;49(5):370-8. doi: 10.1097/MCG.0000000000000307.Malagelada J.R., Bazzoli F., Boeckxstaens G. et al. World gastroenterology organisation global guidelines: dysphagia - global guidelines and cascades update September 2014. J Clin Gastroenterol. 2015 May-Jun;49(5):370-8. doi: 10.1097/MCG.0000000000000307.Morales-Olvera D., Gris-Calvo J.I., García-Romero M.T. Nutritional status of pediatric patients with epidermolysis bullosa. A cross-sectional study. Nutricion Clinica y Dietetica Hospitalaria. 2022;42(1):146-51. doi: 10.12873/421garcia-romero.Morales-Olvera D., Gris-Calvo J.I., García-Romero M.T. Nutritional status of pediatric patients with epidermolysis bullosa. A cross-sectional study. Nutricion Clinica y Dietetica Hospitalaria. 2022;42(1):146-51. doi: 10.12873/421garcia-romero.De Angelis P., Caldaro T., Torroni F. et al. Esophageal stenosis in epidermolysis bullosum: a challenge for the endoscopist. J Pediatr Surg. 2011 May;46(5):842-7. doi: 10.1016/j.jpedsurg.2011.02.017.De Angelis P., Caldaro T., Torroni F. et al. Esophageal stenosis in epidermolysis bullosum: a challenge for the endoscopist. J Pediatr Surg. 2011 May;46(5):842-7. doi: 10.1016/j.jpedsurg.2011.02.017.Mortell A.E., Azizkhan R.G. Epidermolysis bullosa: Management of esophageal strictures and enteric access by gastrostomy. Dermatologic Clinics. 2010;28(2):311-8. doi: 10.1016/j.det.2010.01.012.Mortell A.E., Azizkhan R.G. Epidermolysis bullosa: Management of esophageal strictures and enteric access by gastrostomy. Dermatologic Clinics. 2010;28(2):311-8. doi: 10.1016/j.det.2010.01.012.Nyström A., Thriene K., Mittapalli V., Kern J.S., Kiritsi D., Dengjel J., Bruckner-Tuderman L. Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms. EMBO Mol Med. 2015 Sep;7(9):1211-28. doi: 10.15252/emmm.201505061.Nyström A., Thriene K., Mittapalli V., Kern J.S., Kiritsi D., Dengjel J., Bruckner-Tuderman L. Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms. EMBO Mol Med. 2015 Sep;7(9):1211-28. doi: 10.15252/emmm.201505061.Nyström A., Bruckner-Tuderman L. Injury- and inflammation-driven skin fibrosis: The paradigm of epidermolysis bullosa. Matrix Biol. 2018 Aug;68-69:547-560. doi: 10.1016/j.matbio.2018.01.016.Nyström A., Bruckner-Tuderman L. Injury- and inflammation-driven skin fibrosis: The paradigm of epidermolysis bullosa. Matrix Biol. 2018 Aug;68-69:547-560. doi: 10.1016/j.matbio.2018.01.016.Kiritsi D, Nyström A. Recent advances in understanding and managing epidermolysis bullosa. F1000Res. 2018 Jul 17;7: F1000 Faculty Rev-1097. doi: 10.12688/f1000research.14974.1.Kiritsi D, Nyström A. Recent advances in understanding and managing epidermolysis bullosa. F1000Res. 2018 Jul 17;7: F1000 Faculty Rev-1097. doi: 10.12688/f1000research.14974.1.Bown S.G., Hawes R., Matthewson K. et al. Endoscopic laser palliation for advanced malignant dysphagia. Gut. 1987 Jul;28(7):799-807. doi: 10.1136/gut.28.7.799.Bown S.G., Hawes R., Matthewson K. et al. Endoscopic laser palliation for advanced malignant dysphagia. Gut. 1987 Jul;28(7):799-807. doi: 10.1136/gut.28.7.799.Haynes L. Clinical practice guidelines for nutrition support in Infants and Children with Epidermolysis Bullosa (EB) including THINC (Tool to Help Identify Nutritional Compromise in EB). 2007.Haynes L. Clinical practice guidelines for nutrition support in Infants and Children with Epidermolysis Bullosa (EB) including THINC (Tool to Help Identify Nutritional Compromise in EB). 2007.Jain S.V., Harris A.G., Su J.C., Orchard D., Warren L.J., McManus H., Murrell D.F. The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI): grading disease severity and assessing responsiveness to clinical change in epidermolysis bullosa. J Eur Acad Dermatol Venereol. 2017 Apr;31(4):692-698. doi: 10.1111/jdv.13953.Jain S.V., Harris A.G., Su J.C., Orchard D., Warren L.J., McManus H., Murrell D.F. The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI): grading disease severity and assessing responsiveness to clinical change in epidermolysis bullosa. J Eur Acad Dermatol Venereol. 2017 Apr;31(4):692-698. doi: 10.1111/jdv.13953.Has C., Nyström A., Saeidian A.H., Bruckner-Tuderman L., Uitto J. Epidermolysis bullosa: Molecular pathology of connective tissue components in the cutaneous basement membrane zone. Matrix Biol. 2018 Oct;71-72:313-329. doi: 10.1016/j.matbio.2018.04.001.Has C., Nyström A., Saeidian A.H., Bruckner-Tuderman L., Uitto J. Epidermolysis bullosa: Molecular pathology of connective tissue components in the cutaneous basement membrane zone. Matrix Biol. 2018 Oct;71-72:313-329. doi: 10.1016/j.matbio.2018.04.001.Watanabe M., Natsuga K., Shinkuma S., Shimizu H. Epidermal aspects of type VII collagen: Implications for dystrophic epidermolysis bullosa and epidermolysis bullosa acquisita. J Dermatol. 2018 May;45(5):515-521. doi: 10.1111/1346-8138.14222.Watanabe M., Natsuga K., Shinkuma S., Shimizu H. Epidermal aspects of type VII collagen: Implications for dystrophic epidermolysis bullosa and epidermolysis bullosa acquisita. J Dermatol. 2018 May;45(5):515-521. doi: 10.1111/1346-8138.14222.Kiritsi D., Nyström A. The role of TGFβ in wound healing pathologies. Mechanisms of Ageing and Development. 2018;172:51-8. doi: 10.1016/j.mad.2017.11.004.Kiritsi D., Nyström A. The role of TGFβ in wound healing pathologies. Mechanisms of Ageing and Development. 2018;172:51-8. doi: 10.1016/j.mad.2017.11.004.Atanasova V.S., Russell R.J., Webster T.G. et al. Thrombospondin-1 Is a Major Activator of TGF-β Signaling in Recessive Dystrophic Epidermolysis Bullosa Fibroblasts. J Invest Dermatol. 2019 Jul;139(7):1497-1505.e5. doi: 10.1016/j.jid.2019.01.011.Atanasova V.S., Russell R.J., Webster T.G. et al. Thrombospondin-1 Is a Major Activator of TGF-β Signaling in Recessive Dystrophic Epidermolysis Bullosa Fibroblasts. J Invest Dermatol. 2019 Jul;139(7):1497-1505.e5. doi: 10.1016/j.jid.2019.01.011.Rashidghamat E., McGrath J.A. Novel and emerging therapies in the treatment of recessive dystrophic epidermolysis bullosa.Intractable Rare Dis Res. 2017 Feb;6(1):6-20. doi: 10.5582/irdr.2017.01005.Rashidghamat E., McGrath J.A. Novel and emerging therapies in the treatment of recessive dystrophic epidermolysis bullosa.Intractable Rare Dis Res. 2017 Feb;6(1):6-20. doi: 10.5582/irdr.2017.01005.Couluris M., Kinder B.W., Xu P., Gross-King M., Krischer J., Panos R.J. Treatment of idiopathic pulmonary fibrosis with losartan: a pilot project. Lung. 2012 Oct;190(5):523-7. doi: 10.1007/s00408-012-9410-z.Couluris M., Kinder B.W., Xu P., Gross-King M., Krischer J., Panos R.J. Treatment of idiopathic pulmonary fibrosis with losartan: a pilot project. Lung. 2012 Oct;190(5):523-7. doi: 10.1007/s00408-012-9410-z.Gay-Jordi G., Guash E., Benito B., Brugada J., Nattel S., Mont L., Serrano-Mollar A. Losartan prevents heart fibrosis induced by long-term intensive exercise in an animal model. PLoS One. 2013;8(2): e55427. doi: 10.1371/journal.pone.0055427.Gay-Jordi G., Guash E., Benito B., Brugada J., Nattel S., Mont L., Serrano-Mollar A. Losartan prevents heart fibrosis induced by long-term intensive exercise in an animal model. PLoS One. 2013;8(2): e55427. doi: 10.1371/journal.pone.0055427.MacDonald E.M., Cohn R.D. TGFβ signaling: its role in fibrosis formation and myopathies. Curr Opin Rheumatol. 2012 Nov;24(6):628-34. doi: 10.1097/BOR.0b013e328358df34.MacDonald E.M., Cohn R.D. TGFβ signaling: its role in fibrosis formation and myopathies. Curr Opin Rheumatol. 2012 Nov;24(6):628-34. doi: 10.1097/BOR.0b013e328358df34.Shimada Y.J., Passeri J.J., Baggish A.L. et al. Effects of losartan on left ventricular hypertrophy and fibrosis in patients with nonobstructive hypertrophic cardiomyopathy. JACC Heart Fail. 2013 Dec;1(6):480-7. doi: 10.1016/j.jchf.2013.09.001.Shimada Y.J., Passeri J.J., Baggish A.L. et al. Effects of losartan on left ventricular hypertrophy and fibrosis in patients with nonobstructive hypertrophic cardiomyopathy. JACC Heart Fail. 2013 Dec;1(6):480-7. doi: 10.1016/j.jchf.2013.09.001.Salama Z.A., Sadek A., Abdelhady A.M., Darweesh S.K., Morsy S.A., Esmat G. Losartan may inhibit the progression of liver fibrosis in chronic HCV patients. Hepatobiliary Surg Nutr. 2016 Jun;5(3):249-55. doi: 10.21037/hbsn.2016.02.06.Salama Z.A., Sadek A., Abdelhady A.M., Darweesh S.K., Morsy S.A., Esmat G. Losartan may inhibit the progression of liver fibrosis in chronic HCV patients. Hepatobiliary Surg Nutr. 2016 Jun;5(3):249-55. doi: 10.21037/hbsn.2016.02.06.Geirsson A., Singh M., Ali R. et al. Modulation of transforming growth factor-β signaling and extracellular matrix production in myxomatous mitral valves by angiotensin II receptor blockers. Circulation. 2012 Sep 11;126(11 Suppl 1): S189-97. doi: 10.1161/CIRCULATIONAHA.111.082610.Geirsson A., Singh M., Ali R. et al. Modulation of transforming growth factor-β signaling and extracellular matrix production in myxomatous mitral valves by angiotensin II receptor blockers. Circulation. 2012 Sep 11;126(11 Suppl 1): S189-97. doi: 10.1161/CIRCULATIONAHA.111.082610.Kim M.D., Baumlin N., Yoshida M. et al. Losartan Rescues Inflammation-related Mucociliary Dysfunction in Relevant Models of Cystic Fibrosis. Am J Respir Crit Care Med. 2020 Feb 1;201(3):313-324. doi: 10.1164/rccm.201905-0990OC.Kim M.D., Baumlin N., Yoshida M. et al. Losartan Rescues Inflammation-related Mucociliary Dysfunction in Relevant Models of Cystic Fibrosis. Am J Respir Crit Care Med. 2020 Feb 1;201(3):313-324. doi: 10.1164/rccm.201905-0990OC.Koszegi S., Molnar A., Lenart L. et al. RAAS inhibitors directly reduce diabetes-induced renal fibrosis via growth factor inhibition. J Physiol. 2019 Jan;597(1):193-209. doi: 10.1113/JP277002.Koszegi S., Molnar A., Lenart L. et al. RAAS inhibitors directly reduce diabetes-induced renal fibrosis via growth factor inhibition. J Physiol. 2019 Jan;597(1):193-209. doi: 10.1113/JP277002.Nafar M., Samavat S., Shahraki E. TRANSPLANTATION Downregulation of Profibrotic Gene Expression by Angiotensin Receptor Blockers [Internet]. Vol. 12, Original Paper Iranian Journal of Kidney Diseases. 2018. Available from: www.ijkd.org Accessed: 05.12.2025.Nafar M., Samavat S., Shahraki E. TRANSPLANTATION Downregulation of Profibrotic Gene Expression by Angiotensin Receptor Blockers [Internet]. Vol. 12, Original Paper Iranian Journal of Kidney Diseases. 2018. Available from: www.ijkd.org Accessed: 05.12.2025.Kiritsi D., Schauer F., Gewert S. et al. Safety and tolerability of losartan to treat recessive dystrophic epidermolysis bullosa in children (REFLECT): an open-label, single-arm, phase 1/2 trial. EClinicalMedicine. 2024;77:102900. Published 2024 Oct 30. doi:10.1016/j.eclinm.2024.102900Kiritsi D., Schauer F., Gewert S. et al. Safety and tolerability of losartan to treat recessive dystrophic epidermolysis bullosa in children (REFLECT): an open-label, single-arm, phase 1/2 trial. EClinicalMedicine. 2024;77:102900. Published 2024 Oct 30. doi:10.1016/j.eclinm.2024.102900Orphanet. Losartan [Internet]. [cited 2026 Jan 29]. Available from: https://www.orpha.net/en/drug/substance/137194Orphanet. Losartan [Internet]. [cited 2026 Jan 29]. Available from: https://www.orpha.net/en/drug/substance/137194Orphanet. Inherited epidermolysis bullosa (ORPHA:79361) [Internet]. [cited 2026 Jan 29]. Available from: https://www.orpha.net/en/disease/detail/79361Orphanet. Inherited epidermolysis bullosa (ORPHA:79361) [Internet]. [cited 2026 Jan 29]. Available from: https://www.orpha.net/en/disease/detail/79361DEBRA International. Genetics of EB [Internet]. Vienna (Austria): DEBRA International; [cited 2026 Jan 29]. Available from: https://www.debra-international.org/genetics-of-ebDEBRA International. Genetics of EB [Internet]. Vienna (Austria): DEBRA International; [cited 2026 Jan 29]. Available from: https://www.debra-international.org/genetics-of-eb

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