Analysis of the modern treatment protocols for complicated and uncomplicated infantile hemangiomas. Literature review and own data

Authors

  • O.V. Bogomolets Ukrainian Military Medical Academy, Kyiv, Ukraine https://orcid.org/0000-0001-7869-8443
  • R.V. Hryshchenko Dr. Bogomolets’ Institute of Dermatology and Cosmetology, Kyiv, Ukraine
  • M.V. Pavelko Dr. Bogomolets’ Institute of Dermatology and Cosmetology, Kyiv, Ukraine
  • I.O. Krishchenko Dr. Bogomolets’ Institute of Dermatology and Cosmetology, Kyiv, Ukraine
  • S.O. Bogomolets-Sheremetieva Dr. Bogomolets’ Institute of Dermatology and Cosmetology, Kyiv, Ukraine

DOI:

https://doi.org/10.15574/PS.2023.81.92

Keywords:

infantile hemangioma, ulceration, treatment, β-blocker, surgery, telemedicine, vascular lasers

Abstract

Infantile hemangioma (IH), a benign tumor of the vascular endothelium, is the most common type of vascular pathology of the infant’s skin, which grows and significantly increases in size mostly during the first 12 months of a child's life. Statistics indicate that IH affects up to 10% of newborns and children aged <1 year. The proliferative activity of IHs during the first year of a child's life differs significantly and could mislead parents and doctors. Lack of timely treatment at an early stage leads to an increase in the size of the tumor and high risks of cosmetic defects. Thus, the proliferation of IH can cause a gross deformation of the skin and a dysfunction of nearby organs.

Purpose - to analyze modern data on the treatment of patients with complicated and uncomplicated hemangiomas, to study international experience and compare it with own observations and own experience, and to improve patient treatment protocols.

In this review, we analyzed 19 articles involving more than 2400 children with different types of IH, compared different treatment protocols, their outcomes, and complications, and demonstrated our methods, results, and clinical cases.

It may be resumed that β-blockers are “first-line” drugs for local and systemic treatment of IHs, as they allow slowing of the proliferation and activating resorption of the tumor without cosmetic defects or complications. Treatment of IH in babies following modern treatment protocols should be carried out non-surgically, without operations, anesthesia, scars, or cosmetic defects. Ulceration is the most common complication of IHs and the result of the late start of the treatment and thus could be prevented by the timely beginning of the therapy.

No conflict of interests was declared by the authors.

Author Biographies

O.V. Bogomolets, Ukrainian Military Medical Academy, Kyiv

Academy of Silesia, Katowice, Poland

Dr. Bogomolets’ Institute of Dermatology and Cosmetology, Kyiv, Ukraine

S.O. Bogomolets-Sheremetieva, Dr. Bogomolets’ Institute of Dermatology and Cosmetology, Kyiv

Bogomolets National Medical University, Kyiv, Ukraine

References

Almebayadh M. (2020, Jun). Successful treatment of ulcerated infantile hemangioma with brimonidine-timolol cream: 2 cases report and review of the literature. J Dermatolog Treat. 31(4): 433-434. https://doi.org/10.1080/09546634.2019.1603991; PMid:30973791

Beal BT, Chu MB, Siegfried EC. (2014, Nov-Dec). Ulcerated infantile hemangioma: novel treatment with topical brimonidine-timolol. Pediatr Dermatol. 31(6): 754-756. https://doi.org/10.1111/pde.12420; PMid:25424217

Berk DR, Lehman PA, Franz TJ, Blunt JR, Bayliss SJ. (2013, Jan-Feb). On topical timolol gel-forming solution for infantile hemangiomas. Pediatr Dermatol. 30(1): 160-161. https://doi.org/10.1111/pde.12060; PMid:23316722

Blatt J, Morrell DS, Buck S, Zdanski C, Gold S, Stavas J et al. (2011, Aug). β-blockers for infantile hemangiomas: a single-institution experience. Clin Pediatr (Phila). 50(8): 757-763. https://doi.org/10.1177/0009922811405517; PMid:21525081

Bly RA, Perkins J, Parikh SR. (2017, Jan). Can topical beta-blockers reduce the size of superficial infantile hemangiomas of the head and neck? Laryngoscope. 127(1): 4-5. https://doi.org/10.1002/lary.26350; PMid:27808405 PMCid:PMC5755691

Bogomolets O, Wierzbik-Strońska M, Hryshchenko R, Bogomolets C. (2023, Aug 31). Urgent Treatment of Complicated Ulcerated Infantile Hemangioma with β-Blockers via Telemedicine: A Case Report. Telemed J E Health. doi: 10.1089/tmj.2023.0338. Epub ahead of print. https://doi.org/10.1089/tmj.2023.0338; PMid:37651201

Borok J, Gangar P, Admani S, Proudfoot J, Friedlander SF. (2018, Jan). Safety and efficacy of topical timolol treatment of infantile haemangioma: a prospective trial. Br J Dermatol. 178(1): e51-2. https://doi.org/10.1111/bjd.15865; PMid:28771668

Casiraghi A, Musazzi UM, Rocco P, Franzè S, Minghetti P. (2016). Topical treatment of infantile haemangiomas: A comparative study on the selection of a semi-solid vehicle. Skin Pharmacol Physiol. 29(4): 210-219. https://doi.org/10.1159/000447672; PMid:27532634

Chakkittakandiyil A, Phillips R, Frieden IJ, Siegfried E, Lara-Corrales I, Lam J et al. (2012, Jan-Feb). Timolol maleate 0.5% or 0.1% gel-forming solution for infantile hemangiomas: a retrospective, multicenter, cohort study. Pediatr Dermatol. 29(1): 28-31. https://doi.org/10.1111/j.1525-1470.2011.01664.x; PMid:22150436

Chen L, Tsai TF. (2018, Mar). The role of β-blockers in dermatological treatment: a review. J Eur Acad Dermatol Venereol. 32(3): 363-371. https://doi.org/10.1111/jdv.14566; PMid:28850731

Filoni A, Ambrogio F, De Marco A, Pacifico A, Bonamonte D. (2021, Jul). Topical beta-blockers in dermatologic therapy. Dermatol Ther. 34(4): e15016. https://doi.org/10.1111/dth.15016

Frieden IJ, Haggstrom AN, Drolet BA, Mancini AJ, Friedlander SF, Boon L et al. (2005, Sep-Oct). Infantile hemangiomas: current knowledge, future directions. Proceedings of a research workshop on infantile hemangiomas, April 7-9, 2005, Bethesda, Maryland, USA. Pediatr Dermatol. 22(5): 383-406. https://doi.org/10.1111/j.1525-1470.2005.00102.x; PMid:16190987

Frommelt P, Juern A, Siegel D, Holland K, Seefeldt M, Yu J et al. (2016, Jul). Adverse events in young and preterm infants receiving topical timolol for infantile hemangioma. Pediatr Dermatol. 33(4): 405-414. https://doi.org/10.1111/pde.12869; PMid:27246751

Ge J, Zheng J, Zhang L, Yuan W, Zhao H. (2016, Jan 28). Oral propranolol combined with topical timolol for compound infantile hemangiomas: a retrospective study. Sci Rep. 6: 19765. https://doi.org/10.1038/srep19765; PMid:26819072 PMCid:PMC4730155

Gelmetti C, Cavalli R. (2014, Dec). Beta-blockers for hemangiomas. G Ital Dermatol Venereol. 149(6): 703-709. Epub 2014 Nov 4.

Gong H, Xu DP, Li YX, Cheng C, Li G, Wang XK. (2015, Nov). Evaluation of the efficacy and safety of propranolol, timolol maleate, and the combination of the two, in the treatment of superficial infantile haemangiomas. Br J Oral Maxillofac Surg. 53(9): 836-840. https://doi.org/10.1016/j.bjoms.2015.09.005; PMid:26427968

Hagen R, Ghareeb E, Jalali O, Zinn Z. (2018, Aug). Infantile hemangiomas: what have we learned from propranolol? Curr Opin Pediatr. 30(4): 499-504. https://doi.org/10.1097/MOP.0000000000000650; PMid:29846253

Hasan M, Rahman M, Hoque S, Zahid Hossain AK, Khondker L. (2013, Mar). Propranolol for hemangiomas. Pediatr Surg Int. 29(3): 257-262. https://doi.org/10.1007/s00383-012-3220-5; PMid:23247833

Hermans DJ, Bauland CG, Zweegers J, Van Beynum IM, Van der Vleuten CJ. (2013, Apr). Propranolol in a case series of 174 patients with complicated infantile haemangioma: indications, safety, and future directions. Br J Dermatol. 168(4): 837-843. https://doi.org/10.1111/bjd.12189; PMid:23278381

Horev A, Haim A, Zvulunov A. (2015, Mar). Propranolol induced hypoglycemia. Pediatr Endocrinol Rev. 12(3): 308-310.

Koh SP, Leadbitter P, Smithers F, Tan ST. (2020, Aug). β-blocker therapy for infantile hemangioma. Expert Rev Clin Pharmacol. 13(8): 899-915. https://doi.org/10.1080/17512433.2020.1788938; PMid:32662682

Langley A, Pope E. (2015, Jan). Propranolol and central nervous system function: potential implications for pediatric patients with infantile haemangiomas. Br J Dermatol. 172(1): 13-23. https://doi.org/10.1111/bjd.13379; PMid:25175684

Léauté-Labrèze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taïeb A. (2008, Jun 12). Propranolol for severe hemangiomas of infancy. N Engl J Med. 358(24): 2649-2651. https://doi.org/10.1056/NEJMc0708819; PMid:18550886

Lin Q, Cai B, Shan X, Ni X, Chen X, Ke R, Wang B. (2023). Global research trends of infantile hemangioma: A bibliometric and visualization analysis from 2000 to 2022. Heliyon. 9(11): e21300. https://doi.org/10.1016/j.heliyon.2023.e21300; PMid:37920523 PMCid:PMC10618776

Marey HM, Elmazar HF, Mandour SS, Khairy HA. (2018, Jan 1). Combined oral and topical beta blockers for the treatment of early proliferative superficial periocular infantile capillary hemangioma. J Pediatr Ophthalmol Strabismus. 55(1): 37-42. https://doi.org/10.3928/01913913-20170703-12; PMid:28991344

Mashiah J, Kutz A, Rabia SH, Ilan EB, Goldberg I, Sprecher E et al. (2017, Feb). Assessment of the effectiveness of topical propranolol 4% gel for infantile hemangiomas. Int J Dermatol. 56(2): 148-153. https://doi.org/10.1111/ijd.13517; PMid:28074521

McCuaig CC, Cohen L, Powell J et al. (2013). Therapy of Ulcerated Hemangiomas. Journal of Cutaneous Medicine and Surgery. 17(4): 233-242. https://doi.org/10.2310/7750.2012.12037; PMid:23815955

McMahon P, Oza V, Frieden IJ. (2012, Jan-Feb). Topical timolol for infantile hemangiomas: putting a note of caution in "cautiously optimistic". Pediatr Dermatol. 29(1): 127-130. https://doi.org/10.1111/j.1525-1470.2011.01685.x; PMid:22256996

Munden A, Butschek R, Tom WL, Marshall JS, Poeltler DM, Krohne SE et al. (2014, Apr). Prospective study of infantile haemangiomas: incidence, clinical characteristics and association with placental anomalies. Br J Dermatol. 170(4): 907-913. https://doi.org/10.1111/bjd.12804; PMid:24641194 PMCid:PMC4410180

Novoa M, Baselga E, Beltran S, Giraldo L, Shahbaz A, Pardo-Hernandez H et al. (2018, Apr 18). Interventions for infantile haemangiomas of the skin. Cochrane Database Syst Rev. 4(4): CD006545. https://doi.org/10.1002/14651858.CD006545.pub3; PMid:29667726 PMCid:PMC6513200

Ovadia SA, Landy DC, Cohen ER, Yang EY, Thaller SR. (2015, Feb). Local administration of β-blockers for infantile hemangiomas: a systematic review and meta-analysis. Ann Plast Surg. 74(2): 256-262. https://doi.org/10.1097/SAP.0000000000000390; PMid:25590249

Painter SL, Hildebrand GD. (2016, Jan-Feb). Review of topical beta blockers as a treatment for infantile hemangiomas. Surv Ophthalmol. 61(1): 51-58. https://doi.org/10.1016/j.survophthal.2015.08.006; PMid:26408055

Pope E, Chakkittakandiyil A, Lara-Corrales I, Maki E, Weinstein M. (2013, Jan). Expanding the therapeutic repertoire of infantile haemangiomas: a cohort-blinded study of oral nadolol compared with propranolol. Br J Dermatol. 168(1): 222-224. https://doi.org/10.1111/j.1365-2133.2012.11131.x; PMid:22762503

Pope E, Lara-Corrales I, Sibbald C, Liy-Wong C, Kanigsberg N, Drolet B et al. (2022, Jan 1). Noninferiority and Safety of Nadolol vs Propranolol in Infants With Infantile Hemangioma: A Randomized Clinical Trial. JAMA Pediatr. 176(1): 34-41. https://doi.org/10.1001/jamapediatrics.2021.4565; PMid:34747977 PMCid:PMC8576629

Saint-Jean M, Léauté-Labrèze C, Mazereeuw-Hautier J, Bodak N, Hamel-Teillac D, Kupfer-Bessaguet I et al. (2011, May). Propranolol for treatment of ulcerated infantile hemangiomas. J Am Acad Dermatol. 64(5): 827-832. https://doi.org/10.1016/j.jaad.2010.12.040; PMid:21353332

Soliman YS, Khachemoune A. (2018, Sep 15). Infantile hemangiomas: our current understanding and treatment options. Dermatol Online J. 24(9): 13030/qt5jt8q9km. https://doi.org/10.5070/D3249041401; PMid:30677824

Talaat AA, Elbasiouny MS, Elgendy DS, Elwakil TF. (2012, Apr). Propranolol treatment of infantile hemangioma: clinical and radiologic evaluations. J Pediatr Surg. 47(4): 707-714. https://doi.org/10.1016/j.jpedsurg.2011.10.058; PMid:22498385

Tawfik AA, Alsharnoubi J. (2015, May-Jun). Topical timolol solution versus laser in treatment of infantile hemangioma: a comparative study. Pediatr Dermatol. 32(3): 369-376. https://doi.org/10.1111/pde.12542; PMid:25740672

Wang Y, Zhang X, Yang Y, Zhang J, Yang Y, Lu Y. (2017, Jun). Efficacy and safety of 2% topical propranolol cream for the treatment of proliferating infantile strawberry hemangiomas. Indian J Pediatr. 84(6): 425-429. https://doi.org/10.1007/s12098-017-2303-7; PMid:28194699

Weibel L, Barysch MJ, Scheer HS, Königs I, Neuhaus K, Schiestl C et al. (2016, Mar-Apr). Topical timolol for infantile hemangiomas: evidence for efficacy and degree of systemic absorption. Pediatr Dermatol. 33(2): 184-190. https://doi.org/10.1111/pde.12767; PMid:26840644

Wu HW, Wang X, Zhang L, Zheng JW, Liu C, Wang YA. (2018, Dec 18). Topical timolol vs. oral propranolol for the treatment of superficial infantile hemangiomas. Front Oncol. 8: 605. https://doi.org/10.3389/fonc.2018.00605; PMid:30619747 PMCid:PMC6305365

Xu W, Zhao H. (2022, Nov 29). Management of infantile hemangiomas: Recent advances. Front Oncol. 12: 1064048. https://doi.org/10.3389/fonc.2022.1064048; PMid:36523969 PMCid:PMC9745076

Yilmaz L, Dangoisse C, Semaille P. (2013, Nov-Dec). Infantile hemangioma and propranolol: a therapeutic "revolution". Literature review. Rev Med Brux. 34(6): 479-484.

Yuzuriha S, Nagai F, Noguchi M. (2019, Jun 1). How to manage disfiguring scars in involuted infantile Hemangioma. Adv Wound Care (New Rochelle). 8(6): 221-229. https://doi.org/10.1089/wound.2018.0847; PMid:31737416 PMCid:PMC6855289

Zhang L, Wu HW, Yuan W, Zheng JW. (2017, May 8). Propranolol therapy for infantile hemangioma: our experience. Drug Des Devel Ther. 11: 1401-1408. https://doi.org/10.2147/DDDT.S134808; PMid:28507428 PMCid:PMC5428756

Downloads

Published

2023-12-28