Oral atenolol therapy for proliferating infantile hemangioma

Abstract

Propranolol, a lipophilic nonselective β-blocker, has recently been reported to be the treatment of choice for select types of infantile hemangiomas (IHs). Atenolol is a hydrophilic, selective β1-blocker and therefore may be not associated with side effects attributable to β2-adrenergic receptor blockade and lipophilicity. However, the efficacy and safety of atenolol in the treatment of IH are poorly understood. The aim of this study was to evaluate the efficacy and safety of atenolol in the treatment of proliferating IHs.A study of 76 infants between the ages of 5 to 20 weeks with superficial or mixed IH was conducted between August 2013 and March 2015. Oral atenolol was administered in a progressive schedule to 1 mg/kg per day in a single dose. Efficacy was assessed using the Hemangioma Activity Score (HAS) at weeks 0, 1, 4, 12, and 24. Safety was evaluated at weeks 0, 1, 4, 8, 12, 16, 20, and 24.In total, 70 patients completed 24 weeks of treatment. IH growth abruptly stopped for 93.4% of patients within the fourth week of treatment with atenolol. In ulcerated IHs, complete healing of the ulcerations occurred in an average treatment time of 5.5 weeks. Atenolol treatment promoted dramatic decreases in HAS scores after week 1. An “excellent” treatment response (compete or nearly complete resolution of the IH) was observed in 56.5% of patients at week 24. No significant hypoglycemia, bronchospasm, bradycardia, or hypotension occurred. The most common adverse event was diarrhea, followed by agitation and sleep disturbance.This study demonstrated that atenolol was effective and safe at a dose of 1 mg/kg per day for 24 weeks in the treatment of proliferating IHs.

Jagged1/Notch3 Signaling Modulates Hemangioma-Derived Pericyte Proliferation and Maturation

“…If left untreated, these tumors are characterized by a rapid growth phase during the first year of life, followed by slow involution, which may continue until the age of 7-10 years [1]. In 10% of cases, IHs grow dramatically and destroy tissue, impair function or even threaten life [2,3].…”

Propranolol Suppresses Cobalt Chloride-Induced Hypoxic Proliferation in Human Umbilical Vein Endothelial Cells in vitro

“…In addition, it is reported that β-AR could mediate apoptosis via the Src/MAPK pathway [19,24]. Therefore, propranolol, a commercial nonselective β-AR blocker, is now recommended as an important drug in first-line treatment against IH [25,26]. Although propranolol shows remarkable response rates, there are still some major adverse effects, such as changes in sleep, acrocyanosis, hypotension, and hypoglycemia, which raise serious clinical concerns [27,28].…”

β-Adrenoceptor Blockade for Infantile Hemangioma Therapy: Do β₃-Adrenoceptors Play a Role?

“…That clinical report [1] showing propranolol's spectacular results on IH treatment not only promoted several studies that tested the efficacy of propranolol and other β-blockers for the treatment of IH but also encouraged research on the role of β-adrenoceptors in the pathophysiology of this disease [12,57,58].…”

“…This lack of selectivity makes it difficult to determine the specific β-adrenoceptor subtype directly associated with its therapeutic action. Whatever the case, β-adrenoceptor blockers seem to be effective therapeutic tools for managing IH, for example: (1) propranolol induced a decrease in redness, size, and latency to resolution in IH patients [57][58][59], (2) atenolol induced regression of IH at 4 weeks of treatment in 93.4% of patients [12], (3) acetobutolol was efficient against subglottic IH without side effects [60], and (4) timolol was also effective against superficial IH using 0.5% gel administered topically [61]. Furthermore, positive effects against IH have been seen by combining β-blockers such as oral propranolol plus timolol gel.…”

“…Potential Role of β 3 mainly detected in the head and neck [3], they can appear in other parts of the body such as the airways [8][9][10] and, depending on the location of the lesions, some patients can present dramatic disfigurement, ulcerations, visual compromise, airway and auditory canal obstruction, hypothyroidism, amblyopia, scarring, blindness, and liver or cardiac failure [11][12][13]. In the most dramatic cases, when the lesions invade systemic arteries, the life of the patient may be compromised [14], but only rare cases of death associated with complications in treating IH have been documented [15].…”