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Propranolol treatment for periocular capillary hemangiomas

2010; Elsevier BV; Volume: 14; Issue: 3 Linguagem: Inglês

10.1016/j.jaapos.2010.05.003

1528-3933

Oscar A. Cruz, Elaine C. Siegfried,

Vascular Tumors and Angiosarcomas

In this issue of the Journal of AAPOS, Haider and colleagues1Haider K.M. Plager D.A. Neely D.E. Eikenberry J. Haggstrom A. Outpatient treatment of periocular capillary hemangiomas with propranolol.J AAPOS. 2010; : 251-256Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar reviewed the records of 17 patients administered oral propranolol for the treatment of amblyogenic capillary hemangiomas of the eyelid. Reports of first-line treatment of hemangiomas of infancy have multiplied since the initial report of a small case series of infants who demonstrated a dramatic improvement after treatment with oral propranolol.2Leaute-Labreze C. Dumas de la Roque E. Hubiche F. et al.Propranolol for severe hemangiomas of infancy.N Engl J Med. 2008; 358: 2649-2651Crossref PubMed Scopus (1920) Google Scholar Ironically, propranolol therapy was discovered in that case series because the corticosteroids used to treat large hemangiomas led to cardiac disease, which then created the need for propranolol therapy, which in turn led to regression of the otherwise nonresponsive hemangiomas. As the authors note, a standard of care has not been established for treatment of vision-threatening hemangiomas. A variety of corticosteroid preparations, administered by a variety of routes (topical, injected, or parenteral), have all been considered first-line options. Although corticosteroids can be effective, the optimal molecule, formulation, and dosage has not been defined. Responses are variable, corticosteroids are not well tolerated, and side effects are common. Other medications that have been used to treat hemangiomas—including interferon alpha, cyclophosphamide, and vincristine—carry an even greater risk of adverse effects. When considering any medical treatment, an important confounding variable is timing. Early initiation of treatment may be much more effective to prevent growth than delayed treatment to promote shrinking. Pediatric ophthalmologists who do not participate with or have access to a multidisciplinary, subspecialty service (such as a “vascular anomalies team”) should be familiar with initiating treatment, to avoid delay and risk hemangioma growth, even if the long-term plan is to refer these patients to another provider for medical management. The treatment regimen prescribed by Haider and colleagues appears appropriately conservative, slowly increasing steroid dosing to minimize potential complications. Nonetheless, nearly one-fourth of the patients had problems with medication adherence. Although compliance with recommended treatment by patients is a common, pervasive problem,3Cutler D.M. Everett W. Thinking outside the pillbox—medication adherence as a priority for health care reform.N Engl J Med. 2010; 362: 1553-1555Crossref PubMed Scopus (363) Google Scholar the potential for serious adverse effects mandates better education and vigilance on the part of the prescribing physician. The most common serious adverse effects of propranolol are bradycardia, hypertension, and hypoglycemia. An important confounding safety issue is that propranolol may blunt the early clinical symptoms of these potentially serious side effects. Because hypoglycemia tends to occur in the first few hours after the administration of propranolol, feeding immediately after dosing and regularly every 4 to 6 hours may minimize the risk. Although the pharmacologically optimal dosing interval for propranolol is every 6 hours, compliance is improved if the medication is given every 8 to 12 hours.4Lawley L.P. Siegfried E. Todd J.L. Propranolol treatment for hemangioma of infancy: Risks and recommendations.Pediatr Dermatol. 2009; 26: 610-614Crossref PubMed Scopus (257) Google Scholar The authors make no attempt to elucidate a possible mechanism for propranolol's effects in shrinking hemangiomas of infancy. The effect of propranolol on placenta has been demonstrated when used to treat preeclampsia.5Rouget C. Barthez O. Goirand F. et al.Stimulation of the ADRB3 Adrenergic receptor induces relaxation of human placental arteries: Influence of pre-eclampsia.Biol Reprod. 2006; 74: 209-216Crossref PubMed Scopus (17) Google Scholar Perhaps beta-blockers induce apoptosis by antagonizing Glut-1 receptors or act through other pathways to inhibit growth of the hemangiomas. Topical propranolol has also been shown to reduce oxygen-induced retinopathy in a newborn rat, perhaps through down-regulation of vascular endothelial growth factor.6Ricci B. Ricci F. Maggiano N. Oxygen-induced retinopathy in the newborn rat: Morphological and immunohistological findings in animals treated with topical timolol maleate.Ophthalmologica. 2000; 214: 136-139Crossref PubMed Scopus (17) Google Scholar The results described in this article, although laudable, merit additional scrutiny. Any reduction in the size of a hemangioma greater than 50% was classified as an “excellent result,” which makes it impossible to discern how many of those patients had complete or near complete resolution. In addition, the article does not attempt to define care standards, and so clinicians must carefully consider when to initiate therapy, assess efficacy, adjust dosage, and taper or discontinue the medication on an individual basis until such a standard is defined.4Lawley L.P. Siegfried E. Todd J.L. Propranolol treatment for hemangioma of infancy: Risks and recommendations.Pediatr Dermatol. 2009; 26: 610-614Crossref PubMed Scopus (257) Google Scholar, 7Frieden I.J. Drolet B.A. Propranolol for infantile hemangiomas: Promise, peril, pathogenesis.Pediatr Dermatol. 2009; 26: 642-644Crossref PubMed Scopus (80) Google Scholar The treatment protocol described by Haider and colleagues may not be the best approach for all patients. Eyelid hemangiomas may be equally responsive to topical, rather than systemic, beta-blocker therapy. This theoretically safer route of administration has recently been reported with the use of timolol, a selective beta-blocker formulated as an eyedrop for the treatment of glaucoma. Several studies have now documented the efficacy of topical timolol for superficial and eyelid hemangiomas.8Chakkittakandiyil A. Pope E. Topical timolol gel for infantile hemangiomas—a pilot study.Arch Dermatol. 2010; 146: 564-565PubMed Google Scholar, 9Guo S. Ni N. Topical treatment for capillary hemangioma of the eyelid using beta-blocker solution.Arch Ophthalmol. 2010; 128: 225Google Scholar, 10Frieden I.J. Early laser treatment of periorbital infantile hemangiomas may work, but is it really the best treatment option?.Dermatol Surg. 2010; 36: 598-601Crossref PubMed Scopus (11) Google Scholar We are also aware of an international, multicenter, prospective, randomized, double-masked trial currently underway that will compare a combined regimen of oral propranolol and corticosteroids with corticosteroids alone.11Corticosteroids With Placebo Versus Corticosteroids With Propranolol Treatment of Infantile Hemangiomas (IH). Available at: http://clinicaltrials.gov/ct2/show/NCT01074437?term=propranolol&rank=4. Accessed May 16, 2010.Google Scholar The authors are commended for proposing a uniform outpatient beta-blocker treatment regimen that maximizes the therapeutic outcome while addressing the common known side-effects of therapy in children. As this therapy continues to evolve, we anticipate that it will provide us with a solution to the clinical imperative of a vision-threatening periocular hemangioma. See accompanying report on pages 251-6. Outpatient treatment of periocular infantile hemangiomas with oral propranololJournal of American Association for Pediatric Ophthalmology and Strabismus {JAAPOS}Vol. 14Issue 3PreviewPropranolol has recently been reported to be useful in the treatment of infantile hemangiomas. However, there are still many questions regarding the dosage, duration, and method of delivery. Full-Text PDF ErratumJournal of American Association for Pediatric Ophthalmology and Strabismus {JAAPOS}Vol. 14Issue 4PreviewThe Journal regrets and apologizes for the following error in the June issue: Cruz OA, Siegfried EC. Propranolol treatment for periocular capillary hemangiomas. J AAPOS 2010;14:199-200. The first sentence of the fourth paragraph should read as follows: “The treatment regimen prescribed by Haider and colleagues appears appropriately conservative, slowly increasing propranolol dosing. …” Full-Text PDF