Atenolol as treatment for hepatic hemangiomas in a premature infant

Abstract

An infant of 8-weeks adjusted age born after 24 weeks of gestation was admitted in the neonatal intensive care unit for multiple cutaneous infantile hemangiomas affecting the scalp, torso, and limbs. Abdominal sonography revealed hepatic hemangiomas (Fig. 1). Owing to the presence of multiple comorbidities related to prematurity, particularly bronchopulmonary dysplasia that required oxygen therapy, atenolol was considered a superior option to propranolol due to its selective β1 antagonism. Atenolol commenced at a dosage of 0.25 mg/kg twice daily, which was then increased to 0.5 mg/kg twice daily after 1 week. Repeat sonography at week 18 did not identify any hepatic lesions. At week 19, the infant had been weaned to room air and showed appreciable diminution of the cutaneous hemangiomas. At week 28, the infant was thriving and dosing was changed to 1 mg/kg/day once daily. At 12 months, atenolol administration was ceased without recrudescence of the hemangiomas. Multiple cutaneous hemangiomas are often associated with visceral involvement, especially of the liver.1Rodríguez Bandera A.I. Sebaratnam D.F. Wargon O. Wong L.F. Infantile hemangioma. Part 1: epidemiology, pathogenesis, clinical presentation and assessment.J Am Acad Dermatol. 2021; 85: 1379-1392Google Scholar Such cases commonly require systemic pharmacotherapy with propranolol as the first-line drug. As a lipophilic nonselective β-blocker, propranolol induces a risk of bronchospasm mediated by β2 blockade; adverse outcomes have been reported in preterm infants.2Sebaratnam D.F. Rodríguez Bandera A.L. Wong L.F. Wargon O. Infantile hemangioma. Part 2: management.J Am Acad Dermatol. 2021; 85: 1395-1404Google Scholar Atenolol is a hydrophilic, selective β1 antagonist. A recent systematic review recommended this medication as a safe and effective alternative to propranolol.3Wang Q. Xiang B. Chen S. Ji Y. Efficacy and safety of oral atenolol for the treatment of infantile haemangioma: a systematic review.Australas J Dermatol. 2019; 60: 181-185Google Scholar To the authors' knowledge, the use of atenolol in this setting has not been associated with serious adverse effects, such as bronchospasm, hypotension, bradycardia, and hypoglycemia. Given the severity of the patient's respiratory disease and ongoing need for supplemental oxygen, atenolol medication was commenced at a low dose with slow upward titration. The role of β-blockers in infantile hemangiomas remains a fluid area of research. Recent studies suggested that it is the R(+) rather than S(−) enantiomer of propranolol that exerts its action on hemangiomas by inhibiting the differentiation of hemangioma stem cells to endothelial cells through interference with SOX18 transcriptional activity. Compared with the R(+) enantiomer, the S(−) enantiomer offers weaker blockade of the SOX18 pathway and unlike the R(+) enantiomer has potent anti β-adrenergic effects, which accounts for many of the side effects observed in propranolol. In the future, propranolol formulations composed solely of the R(+) enantiomer may offer a better efficacy and safety profile. To the best of the authors’ knowledge, this report presents the first case of using atenolol as treatment for hepatic hemangiomas. Given its relatively selective mechanism of action and favorable side effect profile, atenolol may be considered for patients with complex medical comorbidities. Concurrently, an argument could be made that “medically brittle” patients warrant an established treatment supported by a great volume of evidence. As a single case report, the conclusions in this study have certain limitations. Nevertheless, this work proposes a biologically plausible argument in favor of atenolol for the management of certain hemangioma cases due to its selective mechanism.