Infantile hemangiomas: from clinical aspects to evolution of pathogenesis understanding and improvement of therapeutic strategies
DOI: 10.32364/2618-8430-2026-9-*-0
Infantile hemangiomas: from clinical aspects to evolution of pathogenesis understanding and improvement of therapeutic strategies
G.V. Kondratiev1, M.E. Melnikov1, Yu.M. Spivakovskiy2
1 Saint Petersburg State Pediatric Medical University, St. Petersburg, Russian Federation
2 V.I. Razumovskiy Saratov State Medical University, Saratov, Russian Federation
Infantile hemangiomas (IH) are the most common benign vascular infantile tumors characterized by variable clinical manifestations and specific natural course patterns which determine an individualized approach to patient management. The paper systematizes and updates data on biological and clinical features of IH. Also, it considers promising therapeutic directions. Special attention is paid to propranolol, a non-selective β-blocker that has become an important tool in systemic therapy of IH, as well as to the analysis of its therapeutic efficacy and practical aspects of the oral solution use. The presented clinical examples highlight a scope of systemic propranolol therapy for IH and demonstrate the importance of timely diagnosis, as well as assessment of indications for the therapy, and an individualized approach to treatment. Modern data generalization provide systematization of knowledge about clinical features, pathogenetic mechanisms, and therapeutic strategies in patients with IH.
Keywords: infantile hemangioma, vascular tumors, β-blockers, propranolol, hemangiol, children, life-threatening conditions.
For citation: Kondratiev G.V., Melnikov M.E., Spivakovskiy Yu.M. Infantile hemangiomas: from clinical aspects to evolution of pathogenesis understanding and improvement of therapeutic strategies. Russian Journal of Woman and Child Health. 2026;9(4):–12 (in Russ.). DOI: 10.32364/2618-8430-2026-9-*-
About the authors:
Gleb V. Kondratiev — Pediatric Oncologist, Assistant, Head of the Teaching Department, Department of Oncology, Pediatric Oncology and Radiation Therapy, Saint Petersburg State Pediatric Medical University; 2, Litovskaya str., St. Petersburg, 194100, Russian Federation; ORCID iD 0000-0002-1462-6907
Maksim E. Melnikov — Pediatric Oncologist, Teaching Assistant of the Department of Oncology, Pediatric Oncology and Radiation Therapy, Saint Petersburg State Pediatric Medical University; 2, Litovskaya str., St. Petersburg, 194100, Russian Federation; ORCID iD 0000-0003-4744-0882
Yurii M. Spivakovskiy — C. Sc. (Med.), Assistant Professor, Head of the Department of Faculty Pediatrics, Director of the University Clinic of Faculty Pediatrics, V.I. Razumovskiy Saratov State Medical University; 112, Bolshaya Kazach'ya str., Saratov, 410012, Russian Federation; ORCID iD 0000-0002-3077-570X
Contact information: Gleb V. Kondratiev, e-mail: spbgvk@mail.ru
Financial Disclosure: no authors have a financial or property interest in any material or method mentioned.
There is no conflict of interest.
Received 20.08.2026.
Revised 14.09.2026.
Accepted 07.10.2026.
References
1. Krowchuk D.P., Frieden I.J., Mancini A.J. et al. Clinical Practice Guideline for the Management of Infantile Hemangiomas. Pediatrics. 2019;143(1):e20183475. DOI: 10.1542/peds.2018-3475
2. Chang L.C., Haggstrom A.N., Drolet B.A. et al. Growth characteristics of infantile hemangiomas: implications for management. Pediatrics. 2008;122(2):360–367. DOI: 10.1542/peds.2007-2767
3. Rešić A., Barčot Z., Habek D. et al. The Evaluation, Diagnosis, and Management of Infantile Hemangiomas — A Comprehensive Review. J Clin Med. 2025;14(2):425. DOI: 10.3390/jcm14020425
4. Хачатрян Л.А., Клецкая И.С. Просто о сложном: инфантильная гемангиома. Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2021;20(1):192–206. DOI: 10.24287/1726-1708-2021-20-1-192-206. Khachatryan L.A., Kletskaya I.S. Simple about complex: infantile hemangioma. Pediatric Hematology/Oncology and Immunopathology. 2021;20(1):192–206 (in Russ.). DOI: 10.24287/1726-1708-2021-20-1-192-206
5. Kunimoto K., Yamamoto Y., Jinnin M. ISSVA Classification of Vascular Anomalies and Molecular Biology. Int J Mol Sci. 2022;23(4):2358. DOI: 10.3390/ijms23042358
6. Mulliken J.B., Glowacki J. Hemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics. Plast Reconstr Surg. 1982;69(3):412–422. DOI: 10.1097/00006534-198203000-00002
7. Jangid S.D., Madke B., Bhatt D., Singh A.L. A Systematic Review on Management of Infantile Hemangiomas: How Far We Have Reached in this Past Decade. Indian Journal of Paediatric Dermatology. 2024;25(3):188–194. DOI: 10.4103/ijpd.ijpd_65_24
8. Neri I., Orioni G., Leuzzi M. et al. Infantile Hemangioma with Minimal or Arrested Growth (IHMAG): A Retrospective Analysis of Clinical and Dermoscopic Diagnostic Clues. Dermatol Pract Concept. 2024;14(3):e2024206. DOI: 10.5826/dpc.1403a206
9. Holm A., Mulliken J.B., Bischoff J. Infantile hemangioma: the common and enigmatic vascular tumor. J Clin Invest. 2024;134(8):e172836. DOI: 10.1172/JCI172836
10. Qiu T., Yang K., Dai S. et al. Clinical Features of Segmental Infantile Hemangioma: A Prospective Study. Ther Clin Risk Manag. 2021;17:119–125. DOI: 10.2147/TCRM.S291059
11. Davenport R., Su J.C., Nathalie J. et al. Clinical overlap of PHACE and LUMBAR syndromes. Pediatr Dermatol. 2022;39(5):752–756. DOI: 10.1111/pde.15031
12. Fernández Faith E., Shah S.D., Braun M. et al. Incidence and clinical factors associated with ulceration in infantile hemangiomas. J Am Acad Dermatol. 2023;88(2):414–420. DOI: 10.1016/j.jaad.2022.10.047
13. Cheng C.E., Friedlander S.F. Infantile hemangiomas, complications and treatments. Semin Cutan Med Surg. 2016;35(3):108–116. DOI: 10.12788/j.sder.2016.050
14. Туркия Л.Р., Муфтахова Г.М., Карманова Д.А. и др. Инфантильная гемангиома и диффузный гемангиоматоз печени у новорожденных с развитием жизнеугрожающих состояний. РМЖ. Мать и дитя. 2025;8(2):173–182. DOI: 10.32364/2618-8430-2025-8-2-10. Turkiya L.R., Muftakhova G.M., Karmanova D.A. et al. Infantile hemangioma and diffuse hepatic hemangiomatosis in newborns with the development of life-threatening conditions. Russian Journal of Woman and Child Health. 2025;8(2):173–182 (in Russ.). DOI: 10.32364/2618-8430-2025-8-2-10
15. Corbeddu M., Meucci D., Diociaiuti A. et al. Management of Upper Airway Infantile Hemangiomas: Experience of One Italian Multidisciplinary Center. Front Pediatr. 2021;9:717232. DOI: 10.3389/fped.2021.717232
16. MacDougall M.S., Afzal S.Y., Freedman M.S. et al. Infant in extremis: respiratory failure secondary to lower airway infantile hemangioma. BMC Pediatr. 2022;22(1):744. DOI: 10.1186/s12887-022-03821-1
17. Zhao J., Huang A.R., Rainer B.M. et al. Periocular infantile hemangiomas: Characteristics, ocular sequelae, and outcomes. Pediatr Dermatol. 2019;36(6):830–834. DOI: 10.1111/pde.13925
18. Sun L., Li Y., Lin X. et al. Periorbital infantile hemangiomas complicated with strabismus. Chin J Plast Reconstr Surg. 2025. DOI: 10.1016/j.cjprs.2025.09.002
19. Tavakoli M., Yadegari S., Mosallaei M. et al. Infantile Periocular Hemangioma. J Ophthalmic Vis Res. 2017;12(2):205–211. DOI: 10.4103/jovr.jovr_66_17
20. Fath L., Simon F., Levy R. et al. Dangers and therapeutic difficulties of intracranial hemangioma in infants: A CARE case report. Eur Ann Otorhinolaryngol Head Neck Dis. 2024;141(4):227–230. DOI: 10.1016/j.anorl.2024.02.001
21. Duffy K.J., Runge-Samuelson C., Bayer M.L. et al. Association of hearing loss with PHACE syndrome. Arch Dermatol. 2010;146(12):1391–1396. DOI: 10.1001/archdermatol.2010.201
22. Braun V., Prey S., Gurioli C. et al. Congenital haemangiomas: a single-centre retrospective review. BMJ Paediatr Open. 2020;4(1):e000816. DOI: 10.1136/bmjpo-2020-000816
23. Хачатрян Л.А., Чиквина И.И., Клецкая И.С. В поисках редкой болезни: врожденные гемангиомы. Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2021;20(1):145–155. DOI: 10.24287/1726-1708-2021-20-1-145-155. Khachatryan L.A., Chikvina I.I., Kletskaya I.S. In search of a rare disease: congenital hemangiomas. Pediatric Hematology/Oncology and Immunopathology. 2021;20(1):145–155 (in Russ.). DOI: 10.24287/1726-1708-2021-20-1-145-155]
24. North P.E., Waner M., Mizeracki A. et al. GLUT1: a newly discovered immunohistochemical marker for juvenile hemangiomas. Hum Pathol. 2000;31(1):11–22. DOI: 10.1016/s0046-8177(00)80192-6
25. Kowalska M., Dębek W., Matuszczak E. Infantile Hemangiomas: An Update on Pathogenesis and Treatment. J Clin Med. 2021;10(20):4631. DOI: 10.3390/jcm10204631
26. Sun Y., Qiu F., Hu C. et al. Hemangioma Endothelial Cells and Hemangioma Stem Cells in Infantile Hemangioma. Ann Plast Surg. 2022;88(2):244–249. DOI: 10.1097/SAP.0000000000002835
27. Zhu Z., Jiang X., Wang F. et al. Decoding infantile hemangioma: cellular dynamics, molecular signals, and microenvironmental influences. Front Oncol. 2025;15:1675194. DOI: 10.3389/fonc.2025.1675194
28. Mitra R., Fitzsimons H.L., Hale T. et al. Recent advances in understanding the molecular basis of infantile haemangioma development. Br J Dermatol. 2024;191(5):661–669. DOI: 10.1093/bjd/ljae241
29. Xiang S., Gong X., Qiu T. et al. Insights into the mechanisms of angiogenesis in infantile hemangioma. Biomed Pharmacother. 2024;178:117181. DOI: 10.1016/j.biopha.2024.117181
30. Itinteang T., Marsh R., Davis P.F. et al. Angiotensin II causes cellular proliferation in infantile haemangioma via angiotensin II receptor 2 activation. J Clin Pathol. 2015;68(5):346–350. DOI: 10.1136/jclinpath-2014-202794
31. Vishvanath A., Itinteang T., Tan S.T. et al. Infantile haemangioma expresses tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), TRAIL receptors, osteoprotegerin and receptor activator for nuclear factor кB ligand (RANKL). Histopathology. 2011;59(3):397–406. DOI: 10.1111/j.1365-2559.2011.03970.x
32. Zhang H., Wei T., Johnson A. et al. NOTCH pathway activation in infantile hemangiomas. J Vasc Surg Venous Lymphat Disord. 2021;9(2):489–496. DOI: 10.1016/j.jvsv.2020.07.010
33. Sun Z.Y., Yi C.G., Zhao H. et al. Infantile hemangioma is originated from placental trophoblast, fact or fiction? Med Hypotheses. 2008;71(3):444–448. DOI: 10.1016/j.mehy.2008.03.013
34. Sun Z.Y., Yang L., Yi C.G. et al. Possibilities and potential roles of estrogen in the pathogenesis of proliferation hemangiomas formation. Med Hypotheses. 2008;71(2):286–292. DOI: 10.1016/j.mehy.2008.02.015
35. Wang W., Chen S., Wang Y. et al. Effects of Notch signaling on proliferation, angiogenesis, and adipogenesis of hemangioma-derived stem cells. Eur J Histochem. 2025;69(3):4241. DOI: 10.4081/ejh.2025.4241
36. Ji Y., Chen S., Li K. et al. Signaling pathways in the development of infantile hemangioma. J Hematol Oncol. 2014;7:13. DOI: 10.1186/1756-8722-7-13
37. Zhang W., Chen G., Wang F.Q. et al. Macrophages Contribute to the Progression of Infantile Hemangioma by Regulating the Proliferation and Differentiation of Hemangioma Stem Cells. J Invest Dermatol. 2015;135(12):3163–3172. DOI: 10.1038/jid.2015.321
38. Xia M., Liu W., Hou F. Mast cell in infantile hemangioma. Front Oncol. 2024;14:1304478. DOI: 10.3389/fonc.2024.1304478
39. Holm A., Mulliken J.B., Bischoff J. Infantile hemangioma: the common and enigmatic vascular tumor. J Clin Invest. 2024;134(8):e172836. DOI: 10.1172/JCI172836
40. Dondon M.G., De Vathaire F., Shamsaldin A. et al. Cancer mortality after radiotherapy for a skin hemangioma during childhood. Radiother Oncol. 2004;72(1):87–93. DOI: 10.1016/j.radonc.2004.03.011
41. Donohue C., Salusti-Simpson M., Bombardier N. et al. Basal cell carcinoma arising at the site of a previously irradiated infantile hemangioma. Pediatr Dermatol. 2024;41(1):145–147. DOI: 10.1111/pde.15403
42. Lundell M., Hakulinen T., Holm L.E. Thyroid cancer after radiotherapy for skin hemangioma in infancy. Radiat Res. 1994;140(3):334–339.
43. Palmer J.D., Tsang D.S., Tinkle C.L. et al. Late effects of radiation therapy in pediatric patients and survivorship. Pediatr Blood Cancer. 2021;68(Suppl 2):e28349. DOI: 10.1002/pbc.28349
44. Beqo B.P., Gasparella P., Flucher C. et al. Indications for surgical resection of complicated infantile hemangiomas in the β-blocker's era: a single-institution experience from a retrospective cohort study. Int J Surg. 2023;109(4):829–840. DOI: 10.1097/JS9.0000000000000324
45. Léauté-Labrèze C., Dumas De la Roque E., Hubiche T. et al. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008;358(24):2649–2651. DOI: 10.1056/NEJMc0708819
46. Rotter A., De Oliveira Z.N.P. Infantile hemangioma: pathogenesis and mechanisms of action of propranolol. J Dtsch Dermatol Ges. 2017;15(12):1185–1190. DOI: 10.1111/ddg.13365
47. Sasaki M., North P.E., Elsey J. et al. Propranolol exhibits activity against hemangiomas independent of beta blockade. NPJ Precis Oncol. 2019;3:27. DOI: 10.1038/s41698-019-0099-9
48. Drolet B.A., Frommelt P.C., Chamlin S.L. et al. Initiation and use of propranolol for infantile hemangioma: report of a consensus conference. Pediatrics. 2013;131(1):128–140. DOI: 10.1542/peds.2012-1691
49. Хачатрян Л.А., Котлукова Н.П., Белышева Т.С. и др. Современная терапия инфантильных гемангиом. Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2021;20(2):156–167. DOI: 10.24287/1726-1708-2021-20-2-156-167. Khachatryan L.A., Kotlukova N.P., Belysheva T.S. et al. Modern treatment of infantile hemangioma. Pediatric Hematology/Oncology and Immunopathology. 2021;20(2):156–167 (in Russ.). DOI: 10.24287/1726-1708-2021-20-2-156-167
50. Léauté-Labrèze C., Hoeger P., Mazereeuw-Hautier J. et al. A randomized, controlled trial of oral propranolol in infantile hemangioma. N Engl J Med. 2015;372(8):735–746. DOI: 10.1056/NEJMoa1404710
51. Котлукова Н.П., Белышева Т.С., Шац Л.И. и др. Возможности медикаментозного лечения инфантильных гемангиом в России. Российский журнал детской гематологии и онкологии. 2022;9(2):22–28. DOI: 10.21682/2311-1267-2022-9-2-22-28. Kotlukova N.P., Belysheva T.S., Shats L.I. et al. Russian Journal of Pediatric Hematology and Oncology. 2022;9(2):22–28 (in Russ.). DOI: 10.21682/2311-1267-2022-9-2-22-28
52. Léauté-Labrèze C., Frieden I., Delarue A. Early initiation of treatment with oral propranolol for infantile hemangioma improves success rate. Pediatr Dermatol. 2023;40(2):261–264. DOI: 10.1111/pde.15198
53. Léauté-Labrèze C., Baselga Torres E., Weibel L. et al. The Infantile Hemangioma Referral Score: A Validated Tool for Physicians. Pediatrics. 2020;145(4):e20191628. DOI: 10.1542/peds.2019-1628
54. Baselga E., Bernabeu-Wittel J., Betlloch Mas I. et al. [Translated article] Update of the Spanish Consensus Document on Infantile Hemangioma. Actas Dermosifiliogr. 2025;116(8):T837–T848. DOI: 10.1016/j.ad.2025.06.017
55. Gong C., Yue X., Zhang L. et al. Prevalence and Risk Factors Associated with the Recurrence of Infantile Hemangiomas After Discontinuation of Propranolol: A Systematic Review and Meta-Analysis. J Clin Med. 2025;14(21):7846. DOI: 10.3390/jcm14217846
56. Pathman L., Simpson J., Penington A.J. et al. Evaluating the Use of Atenolol for the Treatment of Infantile Hemangiomas. Journal of Vascular Anomalies. 2022;3(4):e048. DOI: 10.1097/JOVA.0000000000000048
57. Shi M., Tatian A., Adams S. et al. The Efficacy and Safety of Atenolol for Treatment of Infantile Hemangioma. JEADV Clinical Practice. 2025;5:153–162. DOI: 10.1002/jvc2.70171
58. Salavastru C. Atenolol for Infantile Hemangioma: A Future First-Line Therapy? JEADV Clinical Practice. 2026;5:e70291. DOI: 10.1002/jvc2.70291
59. Muñoz-Garza F.Z., Ríos M., Roé-Crespo E. et al. Efficacy and Safety of Topical Timolol for the Treatment of Infantile Hemangioma in the Early Proliferative Stage: A Randomized Clinical Trial. JAMA Dermatol. 2021;157(5):583–587. DOI: 10.1001/jamadermatol.2021.0596
60. Huang X., Si W., Zou Z. et al. Efficacy and safety of oral propranolol and topical timolol in the treatment of infantile hemangioma: a meta-analysis and systematic review. Front Pharmacol. 2024;15:1515901. DOI: 10.3389/fphar.2024.1515901
61. Xia M., Ding K., Ji Y. et al. The timing and safety of topical timolol treatment for superficial infantile hemangioma: a retrospective cohort study. Eur J Pediatr. 2025;184(2):151. DOI: 10.1007/s00431-025-05983-3
62. Chaple Gil A., Caviedes R., Díaz L. et al. Comparative evaluation of laser therapy for infantile hemangiomas: A systematic review of clinical outcomes and treatment considerations. Photodiagnosis Photodyn Ther. 2025;53:104637. DOI: 10.1016/j.pdpdt.2025.104637
63. Chen Q., Rong H., Liu C. et al. HDAC inhibition reprograms stem cell fate to suppress infantile hemangioma vasculogenesis. Angiogenesis. 2026;29:35. DOI: 10.1007/s10456-026-10057-5
64. Lu W., Yang Z., Wang M. et al. Identification of Potential Therapeutics for Infantile Hemangioma via in silico Investigation and in vitro Validation. Drug Des Devel Ther. 2024;18:4065–4088. DOI: 10.2147/DDDT.S460575
65. Abtahi-Naeini B., Ahmadinia F., Ghorbali F. et al. A Systematic Review of the Efficacy and Safety of Sirolimus (Rapamycin) in the Management of Infantile Hemangioma. J Res Pharm Pract. 2025;14(4):127–133. DOI: 10.4103/jrpp.jrpp_58_25
2. Chang L.C., Haggstrom A.N., Drolet B.A. et al. Growth characteristics of infantile hemangiomas: implications for management. Pediatrics. 2008;122(2):360–367. DOI: 10.1542/peds.2007-2767
3. Rešić A., Barčot Z., Habek D. et al. The Evaluation, Diagnosis, and Management of Infantile Hemangiomas — A Comprehensive Review. J Clin Med. 2025;14(2):425. DOI: 10.3390/jcm14020425
4. Хачатрян Л.А., Клецкая И.С. Просто о сложном: инфантильная гемангиома. Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2021;20(1):192–206. DOI: 10.24287/1726-1708-2021-20-1-192-206. Khachatryan L.A., Kletskaya I.S. Simple about complex: infantile hemangioma. Pediatric Hematology/Oncology and Immunopathology. 2021;20(1):192–206 (in Russ.). DOI: 10.24287/1726-1708-2021-20-1-192-206
5. Kunimoto K., Yamamoto Y., Jinnin M. ISSVA Classification of Vascular Anomalies and Molecular Biology. Int J Mol Sci. 2022;23(4):2358. DOI: 10.3390/ijms23042358
6. Mulliken J.B., Glowacki J. Hemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics. Plast Reconstr Surg. 1982;69(3):412–422. DOI: 10.1097/00006534-198203000-00002
7. Jangid S.D., Madke B., Bhatt D., Singh A.L. A Systematic Review on Management of Infantile Hemangiomas: How Far We Have Reached in this Past Decade. Indian Journal of Paediatric Dermatology. 2024;25(3):188–194. DOI: 10.4103/ijpd.ijpd_65_24
8. Neri I., Orioni G., Leuzzi M. et al. Infantile Hemangioma with Minimal or Arrested Growth (IHMAG): A Retrospective Analysis of Clinical and Dermoscopic Diagnostic Clues. Dermatol Pract Concept. 2024;14(3):e2024206. DOI: 10.5826/dpc.1403a206
9. Holm A., Mulliken J.B., Bischoff J. Infantile hemangioma: the common and enigmatic vascular tumor. J Clin Invest. 2024;134(8):e172836. DOI: 10.1172/JCI172836
10. Qiu T., Yang K., Dai S. et al. Clinical Features of Segmental Infantile Hemangioma: A Prospective Study. Ther Clin Risk Manag. 2021;17:119–125. DOI: 10.2147/TCRM.S291059
11. Davenport R., Su J.C., Nathalie J. et al. Clinical overlap of PHACE and LUMBAR syndromes. Pediatr Dermatol. 2022;39(5):752–756. DOI: 10.1111/pde.15031
12. Fernández Faith E., Shah S.D., Braun M. et al. Incidence and clinical factors associated with ulceration in infantile hemangiomas. J Am Acad Dermatol. 2023;88(2):414–420. DOI: 10.1016/j.jaad.2022.10.047
13. Cheng C.E., Friedlander S.F. Infantile hemangiomas, complications and treatments. Semin Cutan Med Surg. 2016;35(3):108–116. DOI: 10.12788/j.sder.2016.050
14. Туркия Л.Р., Муфтахова Г.М., Карманова Д.А. и др. Инфантильная гемангиома и диффузный гемангиоматоз печени у новорожденных с развитием жизнеугрожающих состояний. РМЖ. Мать и дитя. 2025;8(2):173–182. DOI: 10.32364/2618-8430-2025-8-2-10. Turkiya L.R., Muftakhova G.M., Karmanova D.A. et al. Infantile hemangioma and diffuse hepatic hemangiomatosis in newborns with the development of life-threatening conditions. Russian Journal of Woman and Child Health. 2025;8(2):173–182 (in Russ.). DOI: 10.32364/2618-8430-2025-8-2-10
15. Corbeddu M., Meucci D., Diociaiuti A. et al. Management of Upper Airway Infantile Hemangiomas: Experience of One Italian Multidisciplinary Center. Front Pediatr. 2021;9:717232. DOI: 10.3389/fped.2021.717232
16. MacDougall M.S., Afzal S.Y., Freedman M.S. et al. Infant in extremis: respiratory failure secondary to lower airway infantile hemangioma. BMC Pediatr. 2022;22(1):744. DOI: 10.1186/s12887-022-03821-1
17. Zhao J., Huang A.R., Rainer B.M. et al. Periocular infantile hemangiomas: Characteristics, ocular sequelae, and outcomes. Pediatr Dermatol. 2019;36(6):830–834. DOI: 10.1111/pde.13925
18. Sun L., Li Y., Lin X. et al. Periorbital infantile hemangiomas complicated with strabismus. Chin J Plast Reconstr Surg. 2025. DOI: 10.1016/j.cjprs.2025.09.002
19. Tavakoli M., Yadegari S., Mosallaei M. et al. Infantile Periocular Hemangioma. J Ophthalmic Vis Res. 2017;12(2):205–211. DOI: 10.4103/jovr.jovr_66_17
20. Fath L., Simon F., Levy R. et al. Dangers and therapeutic difficulties of intracranial hemangioma in infants: A CARE case report. Eur Ann Otorhinolaryngol Head Neck Dis. 2024;141(4):227–230. DOI: 10.1016/j.anorl.2024.02.001
21. Duffy K.J., Runge-Samuelson C., Bayer M.L. et al. Association of hearing loss with PHACE syndrome. Arch Dermatol. 2010;146(12):1391–1396. DOI: 10.1001/archdermatol.2010.201
22. Braun V., Prey S., Gurioli C. et al. Congenital haemangiomas: a single-centre retrospective review. BMJ Paediatr Open. 2020;4(1):e000816. DOI: 10.1136/bmjpo-2020-000816
23. Хачатрян Л.А., Чиквина И.И., Клецкая И.С. В поисках редкой болезни: врожденные гемангиомы. Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2021;20(1):145–155. DOI: 10.24287/1726-1708-2021-20-1-145-155. Khachatryan L.A., Chikvina I.I., Kletskaya I.S. In search of a rare disease: congenital hemangiomas. Pediatric Hematology/Oncology and Immunopathology. 2021;20(1):145–155 (in Russ.). DOI: 10.24287/1726-1708-2021-20-1-145-155]
24. North P.E., Waner M., Mizeracki A. et al. GLUT1: a newly discovered immunohistochemical marker for juvenile hemangiomas. Hum Pathol. 2000;31(1):11–22. DOI: 10.1016/s0046-8177(00)80192-6
25. Kowalska M., Dębek W., Matuszczak E. Infantile Hemangiomas: An Update on Pathogenesis and Treatment. J Clin Med. 2021;10(20):4631. DOI: 10.3390/jcm10204631
26. Sun Y., Qiu F., Hu C. et al. Hemangioma Endothelial Cells and Hemangioma Stem Cells in Infantile Hemangioma. Ann Plast Surg. 2022;88(2):244–249. DOI: 10.1097/SAP.0000000000002835
27. Zhu Z., Jiang X., Wang F. et al. Decoding infantile hemangioma: cellular dynamics, molecular signals, and microenvironmental influences. Front Oncol. 2025;15:1675194. DOI: 10.3389/fonc.2025.1675194
28. Mitra R., Fitzsimons H.L., Hale T. et al. Recent advances in understanding the molecular basis of infantile haemangioma development. Br J Dermatol. 2024;191(5):661–669. DOI: 10.1093/bjd/ljae241
29. Xiang S., Gong X., Qiu T. et al. Insights into the mechanisms of angiogenesis in infantile hemangioma. Biomed Pharmacother. 2024;178:117181. DOI: 10.1016/j.biopha.2024.117181
30. Itinteang T., Marsh R., Davis P.F. et al. Angiotensin II causes cellular proliferation in infantile haemangioma via angiotensin II receptor 2 activation. J Clin Pathol. 2015;68(5):346–350. DOI: 10.1136/jclinpath-2014-202794
31. Vishvanath A., Itinteang T., Tan S.T. et al. Infantile haemangioma expresses tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), TRAIL receptors, osteoprotegerin and receptor activator for nuclear factor кB ligand (RANKL). Histopathology. 2011;59(3):397–406. DOI: 10.1111/j.1365-2559.2011.03970.x
32. Zhang H., Wei T., Johnson A. et al. NOTCH pathway activation in infantile hemangiomas. J Vasc Surg Venous Lymphat Disord. 2021;9(2):489–496. DOI: 10.1016/j.jvsv.2020.07.010
33. Sun Z.Y., Yi C.G., Zhao H. et al. Infantile hemangioma is originated from placental trophoblast, fact or fiction? Med Hypotheses. 2008;71(3):444–448. DOI: 10.1016/j.mehy.2008.03.013
34. Sun Z.Y., Yang L., Yi C.G. et al. Possibilities and potential roles of estrogen in the pathogenesis of proliferation hemangiomas formation. Med Hypotheses. 2008;71(2):286–292. DOI: 10.1016/j.mehy.2008.02.015
35. Wang W., Chen S., Wang Y. et al. Effects of Notch signaling on proliferation, angiogenesis, and adipogenesis of hemangioma-derived stem cells. Eur J Histochem. 2025;69(3):4241. DOI: 10.4081/ejh.2025.4241
36. Ji Y., Chen S., Li K. et al. Signaling pathways in the development of infantile hemangioma. J Hematol Oncol. 2014;7:13. DOI: 10.1186/1756-8722-7-13
37. Zhang W., Chen G., Wang F.Q. et al. Macrophages Contribute to the Progression of Infantile Hemangioma by Regulating the Proliferation and Differentiation of Hemangioma Stem Cells. J Invest Dermatol. 2015;135(12):3163–3172. DOI: 10.1038/jid.2015.321
38. Xia M., Liu W., Hou F. Mast cell in infantile hemangioma. Front Oncol. 2024;14:1304478. DOI: 10.3389/fonc.2024.1304478
39. Holm A., Mulliken J.B., Bischoff J. Infantile hemangioma: the common and enigmatic vascular tumor. J Clin Invest. 2024;134(8):e172836. DOI: 10.1172/JCI172836
40. Dondon M.G., De Vathaire F., Shamsaldin A. et al. Cancer mortality after radiotherapy for a skin hemangioma during childhood. Radiother Oncol. 2004;72(1):87–93. DOI: 10.1016/j.radonc.2004.03.011
41. Donohue C., Salusti-Simpson M., Bombardier N. et al. Basal cell carcinoma arising at the site of a previously irradiated infantile hemangioma. Pediatr Dermatol. 2024;41(1):145–147. DOI: 10.1111/pde.15403
42. Lundell M., Hakulinen T., Holm L.E. Thyroid cancer after radiotherapy for skin hemangioma in infancy. Radiat Res. 1994;140(3):334–339.
43. Palmer J.D., Tsang D.S., Tinkle C.L. et al. Late effects of radiation therapy in pediatric patients and survivorship. Pediatr Blood Cancer. 2021;68(Suppl 2):e28349. DOI: 10.1002/pbc.28349
44. Beqo B.P., Gasparella P., Flucher C. et al. Indications for surgical resection of complicated infantile hemangiomas in the β-blocker's era: a single-institution experience from a retrospective cohort study. Int J Surg. 2023;109(4):829–840. DOI: 10.1097/JS9.0000000000000324
45. Léauté-Labrèze C., Dumas De la Roque E., Hubiche T. et al. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008;358(24):2649–2651. DOI: 10.1056/NEJMc0708819
46. Rotter A., De Oliveira Z.N.P. Infantile hemangioma: pathogenesis and mechanisms of action of propranolol. J Dtsch Dermatol Ges. 2017;15(12):1185–1190. DOI: 10.1111/ddg.13365
47. Sasaki M., North P.E., Elsey J. et al. Propranolol exhibits activity against hemangiomas independent of beta blockade. NPJ Precis Oncol. 2019;3:27. DOI: 10.1038/s41698-019-0099-9
48. Drolet B.A., Frommelt P.C., Chamlin S.L. et al. Initiation and use of propranolol for infantile hemangioma: report of a consensus conference. Pediatrics. 2013;131(1):128–140. DOI: 10.1542/peds.2012-1691
49. Хачатрян Л.А., Котлукова Н.П., Белышева Т.С. и др. Современная терапия инфантильных гемангиом. Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2021;20(2):156–167. DOI: 10.24287/1726-1708-2021-20-2-156-167. Khachatryan L.A., Kotlukova N.P., Belysheva T.S. et al. Modern treatment of infantile hemangioma. Pediatric Hematology/Oncology and Immunopathology. 2021;20(2):156–167 (in Russ.). DOI: 10.24287/1726-1708-2021-20-2-156-167
50. Léauté-Labrèze C., Hoeger P., Mazereeuw-Hautier J. et al. A randomized, controlled trial of oral propranolol in infantile hemangioma. N Engl J Med. 2015;372(8):735–746. DOI: 10.1056/NEJMoa1404710
51. Котлукова Н.П., Белышева Т.С., Шац Л.И. и др. Возможности медикаментозного лечения инфантильных гемангиом в России. Российский журнал детской гематологии и онкологии. 2022;9(2):22–28. DOI: 10.21682/2311-1267-2022-9-2-22-28. Kotlukova N.P., Belysheva T.S., Shats L.I. et al. Russian Journal of Pediatric Hematology and Oncology. 2022;9(2):22–28 (in Russ.). DOI: 10.21682/2311-1267-2022-9-2-22-28
52. Léauté-Labrèze C., Frieden I., Delarue A. Early initiation of treatment with oral propranolol for infantile hemangioma improves success rate. Pediatr Dermatol. 2023;40(2):261–264. DOI: 10.1111/pde.15198
53. Léauté-Labrèze C., Baselga Torres E., Weibel L. et al. The Infantile Hemangioma Referral Score: A Validated Tool for Physicians. Pediatrics. 2020;145(4):e20191628. DOI: 10.1542/peds.2019-1628
54. Baselga E., Bernabeu-Wittel J., Betlloch Mas I. et al. [Translated article] Update of the Spanish Consensus Document on Infantile Hemangioma. Actas Dermosifiliogr. 2025;116(8):T837–T848. DOI: 10.1016/j.ad.2025.06.017
55. Gong C., Yue X., Zhang L. et al. Prevalence and Risk Factors Associated with the Recurrence of Infantile Hemangiomas After Discontinuation of Propranolol: A Systematic Review and Meta-Analysis. J Clin Med. 2025;14(21):7846. DOI: 10.3390/jcm14217846
56. Pathman L., Simpson J., Penington A.J. et al. Evaluating the Use of Atenolol for the Treatment of Infantile Hemangiomas. Journal of Vascular Anomalies. 2022;3(4):e048. DOI: 10.1097/JOVA.0000000000000048
57. Shi M., Tatian A., Adams S. et al. The Efficacy and Safety of Atenolol for Treatment of Infantile Hemangioma. JEADV Clinical Practice. 2025;5:153–162. DOI: 10.1002/jvc2.70171
58. Salavastru C. Atenolol for Infantile Hemangioma: A Future First-Line Therapy? JEADV Clinical Practice. 2026;5:e70291. DOI: 10.1002/jvc2.70291
59. Muñoz-Garza F.Z., Ríos M., Roé-Crespo E. et al. Efficacy and Safety of Topical Timolol for the Treatment of Infantile Hemangioma in the Early Proliferative Stage: A Randomized Clinical Trial. JAMA Dermatol. 2021;157(5):583–587. DOI: 10.1001/jamadermatol.2021.0596
60. Huang X., Si W., Zou Z. et al. Efficacy and safety of oral propranolol and topical timolol in the treatment of infantile hemangioma: a meta-analysis and systematic review. Front Pharmacol. 2024;15:1515901. DOI: 10.3389/fphar.2024.1515901
61. Xia M., Ding K., Ji Y. et al. The timing and safety of topical timolol treatment for superficial infantile hemangioma: a retrospective cohort study. Eur J Pediatr. 2025;184(2):151. DOI: 10.1007/s00431-025-05983-3
62. Chaple Gil A., Caviedes R., Díaz L. et al. Comparative evaluation of laser therapy for infantile hemangiomas: A systematic review of clinical outcomes and treatment considerations. Photodiagnosis Photodyn Ther. 2025;53:104637. DOI: 10.1016/j.pdpdt.2025.104637
63. Chen Q., Rong H., Liu C. et al. HDAC inhibition reprograms stem cell fate to suppress infantile hemangioma vasculogenesis. Angiogenesis. 2026;29:35. DOI: 10.1007/s10456-026-10057-5
64. Lu W., Yang Z., Wang M. et al. Identification of Potential Therapeutics for Infantile Hemangioma via in silico Investigation and in vitro Validation. Drug Des Devel Ther. 2024;18:4065–4088. DOI: 10.2147/DDDT.S460575
65. Abtahi-Naeini B., Ahmadinia F., Ghorbali F. et al. A Systematic Review of the Efficacy and Safety of Sirolimus (Rapamycin) in the Management of Infantile Hemangioma. J Res Pharm Pract. 2025;14(4):127–133. DOI: 10.4103/jrpp.jrpp_58_25
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