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Atenolol: A promising alternative to propranolol for the treatment of hemangiomas

2011; Elsevier BV; Volume: 65; Issue: 2 Linguagem: Inglês

10.1016/j.jaad.2010.11.056

1097-6787

Martine F. Raphaël, Marlies de Graaf, Corstiaan C. Breugem, Suzanne G.M.A. Pasmans, Johannes M. P. J. Breur,

Tumors and Oncological Cases

To the Editor: In this issue of the Journal, we report our experience with propranolol as an effective treatment for infantile hemangiomas (IH).1De Graaf M. Breur J.M.P.J. Raphaël M.F. Vos M. Breugem C.C. Pasmans S.G.M.A. Adverse effects of propranolol when used in the treatment of hemangiomas: A case series of 28 infants.J Am Acad Dermatol. 2011; 65: 320-327Abstract Full Text Full Text PDF PubMed Scopus (159) Google Scholar Despite the good results, two patients had to discontinue propranolol treatment because of adverse effects. We hypothesized that the use of a hydrophilic, selective beta-1 blocker could avoid these side effects. We present the preliminary results of the first patients treated with atenolol for IH. Patient 1 presented with a nose tip IH (Cyrano nose) for which propranolol treatment was started at age 3 months. Because of severe bronchial hyperreactivity necessitating hospital admission for oxygen therapy and bronchodilator medications and because of hypotension with diastolic blood pressure around the fifth percentile for age, propranolol was repeatedly discontinued and dosage could not be raised to 2 mg/kg per day. During propranolol treatment, an improvement in volume and color was observed. At age 9 months, treatment with atenolol was started (first 7 days 0.5 mg/kg per day, thereafter 1 mg/kg per day). Atenolol was well tolerated and no bronchial hyperreactivity occurred. Blood pressures remained above the 50th percentile. The hemangioma responded to atenolol (Fig 1) and is currently in regression after 2.5 months of therapy. Patient 2 is a 3½-month-old boy with an ulcerating sacral hemangioma for which ulcer excision was performed and propranolol treatment initiated. During propranolol treatment the boy had problems falling asleep and was restless while sleeping. Discontinuation of propranolol resulted in a normal sleeping pattern. At age 5 months propranolol was restarted at a lower dose of 1 mg/kg per day. The hemangioma responded well, but the side effects reoccurred. Sleep disturbance responded well to cessation of propranolol. Atenolol was subsequently started at age 9 months (first 7 days 0.5 mg/kg per day, thereafter 1 mg/kg per day). No side effects occurred. Follow-up at the age of 10½ months showed further regression of the hemangioma (Fig 2). Propranolol, a lipophilic nonselective beta-blocker, has been introduced as an effective treatment for IH.2Léauté-Labrèze C. Dumas de la Roque E. Hubiche T. Boralevi F. Thambo J.B. Taïeb A. Propranolol for severe hemangiomas of infancy.N Engl J Med. 2008; 358: 2649-2651Crossref PubMed Scopus (1849) Google Scholar The effect of propranolol might be attributed to beta-2 blockage in the endothelial cell resulting in vasoconstriction, inhibition of angiogenesis, and induction of apoptosis.3Storch C.H. Hoeger P.H. Propranolol for infantile haemangiomas: insights into the molecular mechanisms of action.Br J Dermatol. 2010; 163: 269-274Crossref PubMed Scopus (418) Google Scholar Despite excellent results, we observed serious side effects.1De Graaf M. Breur J.M.P.J. Raphaël M.F. Vos M. Breugem C.C. Pasmans S.G.M.A. Adverse effects of propranolol when used in the treatment of hemangiomas: A case series of 28 infants.J Am Acad Dermatol. 2011; 65: 320-327Abstract Full Text Full Text PDF PubMed Scopus (159) Google Scholar We hypothesized that the use of a hydrophilic beta-1 antagonist could avoid the adverse events observed during propranolol therapy. Hydrophilic beta-blockers, which appear at low concentrations in brain tissue, are less likely to produce central nervous system–related side effects (nightmares and hallucinations) than lipophilic beta-blockers, which occur at higher concentrations in the brain.4Westerlund A. Central nervous system side-effects with hyodrophilic and lipophilic beta-blockers.Eur J Clin Pharmacol. 1985; 28: 73-76Crossref PubMed Scopus (69) Google Scholar In addition, atenolol is less likely to produce pulmonary side effects.5Doshan H.D. Rosenthal R.R. Brown R. Slutsky A. Applin W.J. Caruso F.S. Celiprolol, atenolol and propranolol: a comparison of pulmonary effects in asthmatic patients.J Cardiovas Pharmacol. 1986; 8: 105-108Crossref PubMed Scopus (46) Google Scholar Therefore atenolol was started during hospital admission in two patients who had to discontinue propranolol due to side effects. Follow-up visits for effects and side effects were frequently performed by experienced dermatologists and pediatricians in the outpatient clinic. These visits included obtaining medical history and physical examination with monitoring of blood pressure and heart rate. Serum glucose values were obtained during the first week of treatment. Both patients tolerated atenolol very well and no adverse events occurred. Furthermore, the hemangiomas responded well on atenolol therapy, although maybe slightly slower, as seen in patient 1. A possible explanation for the observed effect is the limited beta-2 blocking potential of atenolol.6Hansson L. Aberg H. Karlberg B.E. Westerlund A. Controlled study of atenolol in treatment of hypertension.Br Med J. 1975; 2: 367-370Crossref PubMed Scopus (62) Google Scholar This may also explain why the spectacular discoloration of the IH in the early phase of therapy (early vasoconstriction) was not observed.7Golf S. Bjornerheim R. Erichsen A. Hansson V. Relative selectivity of different beta-adrenoceptor antagonists for human heart beta 1- and 2-receptor subtypes assayed by radioligand binding technique.Scand J Clin Lab Invest. 1987; 47: 719-723Crossref PubMed Scopus (2) Google Scholar Another explanation for the effect is that we observed the natural course of IH in two patients. However, the change in clinical course after initiation of atenolol makes this unlikely. Finally, there may be currently unknown pathways through which beta-blockers mediate their effect on IH. A randomized controlled clinical trial should be conducted to prove the equal efficacy and better tolerance of atenolol compared with propranolol. Adverse effects of propranolol when used in the treatment of hemangiomas: A case series of 28 infantsJournal of the American Academy of DermatologyVol. 65Issue 2PreviewInfantile hemangioma (IH) is a frequently encountered tumor with a potentially complicated course. Recently, propranolol was discovered to be an effective treatment option. Full-Text PDF