Subscribe to RSS
DOI: 10.1055/a-1645-1665
Topical Timolol for Infantile Haemangioma of the Orbit
Timololtropfen für infantile Hämangiome der Orbita![](https://www.thieme-connect.de/media/klimo/202110/lookinside/thumbnails/10-1055-a-1645-1665_kl2508-1.jpg)
Abstract
Infantile haemangiomas (IHs) are the most common benign tumours of the eyelid and orbits in infancy. Beta-blockers, in the form of oral propranolol, have become first-line treatment in severe cases with functionally significant or disfiguring IH. However, adverse drug reactions of oral propranolol in infants are reported in 1 in 11 and serious or potentially life-threatening systemic side effects in 1 in 38, including dyspnoea, hypotension, hyperkalaemia, hypoglycaemia, and cyanosis, therefore requiring careful and close monitoring during the course of systemic treatment. More recently, two large meta-analyses have shown topical beta-blockers, such as timolol maleate 0.5%, to be as effective as oral propranolol in superficial IH, but with no or significantly fewer adverse effects, and have advocated that topical beta-blockers replace oral propranolol as the first-line treatment of superficial IH. We have previously reported the therapeutic response of deep periocular IH to primary topical timolol maleate 0.5% monotherapy. Here we also describe the first successful treatments of large orbital IHs with primary topical timolol maleate 0.5% monotherapy in four infants, resulting in immediate cessation of progression and rapid clinical improvement or resolution in all cases. No adverse effects and no recurrence during long-term follow-up of up to 2.5 years after cessation were seen in any of the patients treated with topical timolol maleate 0.5%.
Zusammenfassung
Infantile Hämangiome (IH) sind die häufigsten gutartigen Tumoren des Augenlids und der Augenhöhlen im Säuglingsalter. Betablocker in Form von oralem Propranolol sind in schweren Fällen mit funktionell signifikantem oder entstellendem IH zur Erstlinienbehandlung geworden. Unerwünschte Arzneimittelnebenwirkungen von oralem Propranolol werden jedoch in 1 von 11 Säuglingen und schwerwiegende oder potenziell lebensbedrohliche Nebenwirkungen in 1 von 38 Säuglingen berichtet, einschließlich Dyspnoe, Hypotonie, Hyperkaliämie, Hypoglykämie und Zyanose, die daher eine sorgfältige und genaue Überwachung während der oralen Behandlung erfordern. In jüngerer Zeit haben 2 große Metaanalysen gezeigt, dass topische Betablocker wie Timololmaleat 0,5% bei oberflächlichem IH genauso wirksam sind wie orales Propranolol, jedoch ohne oder mit signifikant weniger Nebenwirkungen, und befürworten die Ersetzung von oralem Propranolol durch topische Betablocker als Erstlinienbehandlung von oberflächlichem IH. Wir haben bereits über das therapeutische Ansprechen von tiefen periokulären IH auf eine primäre topische Timololmaleat-0,5%-Monotherapie berichtet. Hier beschreiben wir die ersten erfolgreichen Behandlungen von großen orbitalen IH mit topischem Timololmaleat 0,5% bei 4 Säuglingen, was in allen Fällen zu einem sofortigen Ende des klinischen Fortschreitens und einer schnellen klinischen Verbesserung oder vollständigen Heilung führte. Bei keinem der Patienten, die mit topischem Timololmaleat 0,5% behandelt worden waren, wurden während der Behandlung Nebenwirkungen oder nach Beendigung der Behandlung während der Langzeitnachbeobachtung von bis zu 2,5 Jahren ein Wiederauftreten beobachtet.
Key words
topical timolol - beta-blockers - orbital infantile hemangioma - orbital infantile haemangioma - orbital capillary haemangiomaSchlüsselwörter
Timololtropfen - Betablocker - orbitales infantiles Hämangiom - orbitales kapilläres HämangiomPublication History
Received: 08 September 2021
Accepted: 10 September 2021
Article published online:
18 October 2021
© 2021. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Low CM, Stokken JK. Typical Orbital Pathologies: Hemangioma. J Neurol Surg B Skull Base 2021; 82: 20-26
- 2 Anderson KR, Schoch JJ, Lohse C. et al. Increasing incidence of infantile hemangiomas over the past 35 years: Correlation with decreasing gestational age at birth and birth weight. J Am Acad Dermatol 2016; 74: 120-126
- 3 Hoornweg MJ, Smeulders MJ, Ubbink DT. et al. The prevalence and risk factors of infantile haemangiomas: a case-control study in the Dutch population. Paediatr Perinat Epidemiol 2012; 26: 156-162
- 4 Prey S, Voisard JJ, Delarue A. et al. Safety of propranolol therapy for severe infantile hemangioma. JAMA 2016; 315: 413-415
- 5 Martin K. Chapter 669. Vascular Disorders. In: Kliegman RM, Geme JS. eds. Nelson textbook of pediatrics. Philadelphia: Elsevier; 2020: 3461-3469
- 6 Léauté-Labrèze C, Dumas de la Roque E, Hubiche T. et al. Propranolol for severe hemangiomas of infancy. N Engl J Med 2008; 358: 2649-2651
- 7 Guo S, Ni N. Topical treatment for capillary hemangioma of the eyelid using beta-blocker solution. Arch Ophthalmol 2010; 128: 255-256
- 8 Lin Z, Zhang B, Yu Z. et al. The effectiveness and safety of topical β-receptor blocker in treating superficial infantile haemangiomas: A meta-analysis including 20 studies. Br J Clin Pharmacol 2020; 86: 199-209
- 9 Wang X, Feng W, Zhao X. et al. The Efficacy and Safety of Topical β-Blockers in Treating Infantile Hemangiomas: A Meta-Analysis Including 11 Randomized Controlled Trials. Dermatology 2021; 237: 433-443
- 10 Püttgen K, Lucky A, Adams D. et al. Topical timolol maleate treatment of infantile hemangiomas. Pediatrics 2016; 138: 1-9
- 11 Painter SL, Hildebrand GD. Review of topical beta blockers as treatment for infantile hemangiomas. Surv Ophthalmol 2016; 61: 51-58
- 12 Sipkova Z, Xue K, Mudhar HS. et al. Early and Late Histological and Ultrastructural Findings in Resected Infantile Capillary Hemangiomas Following Treatment with Topical Beta-Blocker Timolol Maleate 0.5. Ocul Oncol Pathol 2018; 4: 100-106
- 13 Hassanein AH, Fishman SJ, Mulliken JB. et al. Metastatic neuroblastoma mimicking infantile hemangioma. J Pediatr Surg 2010; 45: 2045-2049
- 14 Fernandez CC, Rodriguez MF, Bandera AR. et al. Metastatic neuroblastoma mimicking an infantile hemangioma. Pediatr Dermatol 2021; 38: 316-317
- 15 Bakalli I, Kola E, Lluka R. et al. Deep coma in a child treated with propranolol for infantile hemangioma. BMC Pediatr 2019; 19: 216
- 16 Ganigara A, Ravishankar C, Ramavakoda C. et al. Fatal hyperkalemia following succinylcholine administration in a child on oral propranolol. Drug Metab Pers Ther 2015; 30: 69-71
- 17 Xue K, Hildebrand GD. Deep periocular infantile capillary hemangiomas responding to topical application of timolol maleate, 0.5 %, drops. JAMA Ophthalmol 2013; 131: 1246-1248
- 18 Painter SL, Hildebrand GD. Topical timolol maleate 0.5 % solution for the management of deep periocular infantile hemangiomas. J AAPOS 2016; 20: 172-174
- 19 Xue K, Hildebrand GD. Topical timolol maleate 0.5 % for infantile capillary haemangioma of the eyelid. Br J Ophthalmol 2012; 96: 1536-1537
- 20 Wu HW, Wang X, Zhang L. et al. Topical Timolol vs. Oral Propranolol for the Treatment of Superficial Infantile Hemangiomas. Front Oncol 2018; 8: 1-6
- 21 Jefferson R, Hildebrand GD. Topical timolol treatment for periocular infantile haemangioma in the developing world. Trop Doct 2019; 49: 246-248