Late Rebound of Infantile Hemangioma after Cessation of Oral Propranolol

Abstract

Propranolol has become the first line of treatment for infantile hemangiomas (IHs), with a high response rate, but rebound growth after cessation of propranolol has been reported, primarily in the first year of life. We sought to determine the frequency and associated factors leading to late regrowth after successful treatment at an age when the proliferative phase has usually ceased. We retrospectively reviewed the clinical charts, serial photographs, and radiologic images of children with rebound IH occurring after the age of 15 months after a successful course of oral propranolol averaging 2.6 mg/kg/day (range 2-3 mg/kg/day). Thirteen (10 female, 3 male) of 212 patients (6%) treated with oral propranolol since 2008 were evaluated. The mean age at the start of treatment was 5.3 months (range 1.8-13 months), and an average of 10.3 months (range 4.5-16 months) of treatment was given. It took an average of 5.3 months (range 1-13.8 months) for a significant rebound to appear. Late rebound after successful propranolol indicates a prolonged proliferation phase of IH even after 15 months of age. This is compared with previous reports of rebound, which occurred primarily in infants younger than 1 year old. Late proliferation can occur in localized, small, mixed, and deep IH, even after several months of a positive response to propranolol. A second course of propranolol readily controlled the recurrence.

Hemangiomas and β-Blockers: On the Rebound

“…Their finding of increased rebound in deep or mixed IH and segmental IH is consistent with other reports, [6][7][8] as is the increased risk of rebound observed in girls 2,[6][7][8] The aforementioned hemangioma subtypes may represent a unique subpopulation of IH programmed to proliferate longer. 11,12 In a series of IH with prolonged growth by Brandling-Bennett et al, 11 all 23 lesions were on the head and neck, another feature found in the current study; in that series, nearly 40% of IH involved the parotid gland, a detail not included in the current report.…”

“…Several previous studies report a higher rebound rate with shorter durations of OP therapy, 2, 6, 13 although in others this association is less clear. 7 …”

“…One limitation that has become clearer with accumulating clinical experience, though, is that of potential rebound IH growth after OP, estimated to occur in 6% to 25% of children. 2,[5][6][7][8][9] Understanding the phenomenon of postpropranolol rebound, and being able to predict or (better yet) prevent it, will increase clinical success and parental satisfaction with OP therapy and, in some instances, help prevent morbidity (such as airway blockage resulting from subglottic IH rebound).…”

Diagnosis and Management of Infantile Hemangioma

“…Rebound growth of IH has been observed in 6% to 25% of children, often well after their first birthday, leading some clinicians to wean propranolol over weeks to months. [185][186][187][188][189] Rebound growth may be more likely in patients whose IH exhibited a long proliferative stage and a large subcutaneous component. 185 In such cases, reinitiation of therapy for variable periods of time may be necessary.…”

Wnt3a Expression is Associated with MMP-9 Expression in Primary Tumor and Metastatic Site in Recurrent or Stage IV Colorectal Cancer

“…β-blockers have recently been introduced as a safe and effective treatment for IH [8][9][10][11]. However, their use is not without risk, and not all tumors respond to these drugs [12,13]. These issues have spurred extensive research to clarify the signaling pathways implicated in hemangioma neovascularization in the hope that a greater understanding of its molecular pathogenesis will reveal new strategies to tackle IH.…”