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Hemangiomas Treated with
Propranolol: Do the Rewards
Outweigh the Risks?

Kathryn M. Haider, M.D.
Daniel E. Neely, M.D.
David A. Plager, M.D.
Recent reports of propranolol for the treatment of heman- giomas have led many physicians to question the best treat-ment strategy for children with vision- threatening heman-giomas. Although propranolol has potential side effects, including hypoglycemia and hypotension, early studies suggest it is more effi cacious than systemic cortico steroids with a lower incidence of adverse side effects.
led many physicians to question the best treatment strategy for children with hem- treatment because they will eventually re- tism, anisometropia, painful ulceration, impairment. Recent reports of propranolol or signifi cant facial disfi gurement. As oph- thalmologists, we treat vision- threatening hemangiomas because long after the hem-angiomas regress, the lasting effects of From the Glick Eye Institute, Indianapolis, Indiana.
amblyopia and vision loss can remain.
Requests for reprints should be addressed to: Kathryn M. Haider, M.D., Glick Eye Institute, 1160 West Michigan #220, Indiana University, Indianapolis, IN 46202; e-mail: Presented as part of a Symposium of the Joint Meeting of the classic presentations: superfi cial, subcu- American Orthoptic Council, the American Association of Certifi ed Orthoptists, and the American Academy of Oph- taneous, and orbital. Superfi cial lesions thalmology, Chicago, Illinois, November 11, 2012.
fi rst appear as fl at, red “birthmarks” that 2013 Board of Regents of the University of Wisconsin System, American Orthoptic Journal, Volume 63, 2013, ISSN 0065-955X, E-ISSN 1553-4448 can grow to become elevated, “strawberry” red, and shiny. As they regress, the color sociated with signifi cant systemic side angiomas often appear bluish, purple in color, and may enlarge with valsalva. They typically feel soft. Orbital hemangiomas may be associated with both superfi cial or Léauté- Labrèze et al. fi rst reported their serendipitous discovery of propranolol as ent with isolated proptosis. Radiographi- a treatment for infantile hemangiomas in cal imaging can help delineate the extent of a hemangioma, especially when there is treated with systemic steroids but devel- oped obstructive hypertropic myocardiopa- thy. The child was subsequently placed on therapy, topical corticosteroids, inject- propranolol. A second boy had a plaque- like able corticosteroids, surgical excision, infantile hemangioma affecting the right face as well as a mass that compressed his trachea and esophagus. His initial treat- ment also included systemic steroids, but treated with local therapy. Systemic ther- apy is generally effective, but also has a creased cardiac output. Both children had host of side effects, including adrenal sup- pression, growth retardation, cushingoid appearance, gastrointestinal intolerance, infections, and delays in routine immuni- Since this fi rst report in 2008, there has zations. Topical corticosteroids can work been an explosion in the literature on this they are not ideal for very large or deep this medication for the treatment of infan- lesions. Injectable corticosteroids are best tile hemangiomas has likely seen its dra- used with discrete subcutaneous lesions. matic and rapid effect on halting the pro- gression and sometimes marked regression ment, typically within 2 to 4 weeks. This approach is logistically diffi cult for very know about this systemic drug we are giv- large, orbital lesions or mainly superfi - cial lesions. Potential side effects include blocker that was fi rst introduced in the deposits, fat atrophy, and central retinal 1960s. It has effects on the heart, lungs, artery occlusion.1, 2 While the fi rst three effects most often resolve with time, the artery occlusion because it can result in permanent and complete vision loss. This complication is likely rare, but the true intestinal disturbance, and rash. In 2003, is an excellent option for subcutaneous, well- circumscribed lesions, but is not an ideal choice for superfi cial or orbital tu- diovascular morbidity as a direct result of beta- blocker exposure is to be found in English- language review for children un- provement, there was a clear benefi t of lished a case series in 2010 outlining our steroids (29%) alone. They also reviewed side effects and cost. Adverse effects of outpatient basis.7 Briefl y, it consisted of propranolol were reported at 1%, while for baseline vital signs and EKG. If normal, corticosteroids were 100%. The cost of pro- grams/ day divided three times a day and increased to 2.0 mg/ kilograms/ day divided controlled, parallel- group trial of propran- three times a day. Families were counseled lished by Hogeling et al. in 2011.10 They sion and hypoglycemia including lethargy, reported on thirty-nine patients. Patients restlessness, decreased heart rate, cool treated with propranolol had a signifi cant clammy skin, delayed capillary refi ll, and decreased appetite. Patients are monitored to placebo (14 vs. 60 %, respectively). In by their pediatrician after each increase in addition, there were no reports of hypoten- dose. We evaluated patients every 2 to 3 weeks initially and then every 3 to 8 weeks But side effects can happen. The fi rst re- subsequently. The youngest child started port of complications related to proprano- was 3 weeks of age and the oldest was 12 lol therapy for hemangiomas was in 2009. months. The results were excellent. Ten of Lawley et al. reported on an 8-week- old girl 17 patients had a greater than 50% reduc- started on 2 mg/ kilogram/ day divided twice tion in size. Six of 17 had “good” results defi ned as less than 50% reduction in size. was not responsive to corticosteroids.11 Af- One patient had “fair” results defi ned as no ter her second dose, she developed lethargy progression although no reduction in size. and cold hands and feet. She was taken to No patients had progression or intolerable found to be 87 and her systolic blood pres- sure was 60. Her vital signs and symptoms normalized in two hours without specifi c systematic review of the use of proprano- intervention. They also describe a former lol in the management of periocular capil- on 2 mg/ kilogram/ day divided three times case reports or case series all describing a day of propranolol for a diagnosis of dis- tunately, the largest case series included only eighteen patients and each paper had have a blood glucose level of 48. Proprano- variable age of presentation, dose, and du- lol was continued because the patient was asymptomatic and was growing well at the Price et al. in 2011.9 They reviewed 110 pa- Holland et al. reported three additional tients treated with one of three treatment modalities: oral corticosteroids, proprano- lished case reports of children receiving lol without corticosteroids, and propran- olol with previous corticosteroids. When defi ning success as greater than 75% im- panolol dose greater than 4 mg/ kilogram/ into an eyelid capillary hemangioma. Am J Oph-thalmol 1996; 121:638-642.
associated with prolonged fasting or poor 3. Walker RS, Custer PL, Nerad JA: Surgical exci- oral intake, although there were rare ex- sion of periorbital capillary hemangiomas. Oph- thalmology 1994; 101:1333-1340.
4. Plager DA, Snyder SK: Resolution of astigmatism after surgical resection of capillary hemangiomas in infants. Ophthalmology 1997; 104:1102-1106.
biche T, Boralevi F, Thambo JB, Taïeb A: Pro- pranolol for severe hemangiomas of infancy. N Engl J Med 2008; 358:2649-2651.
6. Love JN, Sikka N: Are 1-2 tablets dangerous? Beta blocker exposure in toddlers. J Emerg Med systemic corticosteroids, although larger 7. Haider KM, Plager DA, Neely DE, Eikenberry J, all children respond equally. The risks of Haggstrom A: Outpatient treatment of periocu- lar infantile hemangiomas with oral propranolol. although the incidence is low. Parents and 8. Spiteri Cornish K, Reddy AR: The use of pro- providers need to be aware of this potential pranolol in the management of periocular capil- lary hemangioma: A systematic review. Eye 2011; 9. Price CJ, Lattouf C, Baum B, McLeod M, steroids. Our results suggest propranolol Schachner LA, Duarte AM, Connelly EA: Pro-pranolol vs. corticosteroids for infantile hem- has replaced systemic corticosteroids for angiomas: A multicenter retrospective analysis. Arch Dermatol 2011; 147:1371-1376.
10. Hogeling M, Adams S, Wargon O: A randomized vation, topical corticosteroids, injectable controlled trial of propranolol for infantile hem- corticosteroids, and resection still play a angiomas. Pediatrics 2011; 128:e259-266.
11. Lawley LP, Siegfried E, Todd JL: Propranolol role. As health care providers, we are still treatment for hemangioma of infancy: Risks charged with fi nding the best treatment and recommendations. Pediatr Dermatol 2009; 12. Holland KE, Frieden IJ, Frommelt PC, Man- cini AJ, Wyatt D, Drolet BA: Hypoglycemia in children taking propranolol for the treatment of infantile hemangioma. Arch Dermatol 2010; 1. Ruttum MS, Abrams GW, Harris GJ, Ellis MK: Bilateral retinal embolization associated with intralesional corticosteroid injection for capillary hemangioma of infancy. J Pediatric Ophthalmol Key words: infantile hemangioma,
2. Egbert JE, Schwartz GS, Walsh AW: Diagnosis and treatment of ophthalmic artery occlusion during an intralesional injection of corticosteroid


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