Discussion
In 2008, Léauté-Labrèze et al reported the efficacy of propranolol as a treatment for IH. Numerous articles have since been published on this treatment modality, with the majority reporting positive outcomes with propranolol use and IH in their patient populations 9. Propranolol has become the first-line treatment for problematic hemangiomas, and its high efficacy and minimal adverse effects have been extensively demonstrated. Additional treatment modalities include laser therapy, surgical excision, and intralesional steroid injections. Pulse dye laser is the most used in the management of IH and is effectively used to remove the residual telangiectasias during involution and to promote wound healing of ulcerated hemangiomas that are unresponsive to medical management 10. Surgery should be considered in some cases when it would lead to better results than the process of involution or medical therapy, although timing remains controversial1.
This study confirms previous findings that suggest IH are more frequently associated with white non-Hispanic ethnicity and female sex. In prior literature, about 60% of lesions involve the head and neck, followed by 25% on the trunk and 15% on the extremities1,11,12. In our study, however, our cohort had a much higher percentage of head and neck lesions, representing about 90% of all IH. Morphologically, we found focal lesions were the most common in our cohort, aligning with previous findings 12,13.
PHACE syndrome is characterized by vascular cutaneous and nerve lesions of multiple systematic systems, which often cause structural or functional impairments 14. Another study found that PHACE syndrome was more frequently observed in patients with large segmental facial hemangiomas 15. In our cohort, 10% of patients had a diagnosis of PHACE syndrome and we found a statistically significant association between head/facial lesions and a diagnosis of PHACE syndrome. However, we did not find a statistically significant association between PHACE syndrome and size distribution. Additionally, the most common treatment indication was cosmetic disfigurement with most patients initiating treatment before 6 months of age. Although protocols for propranolol administration vary per institution, the dosage administered is usually 1-3mg/kg daily, with most physicians favoring 2mg/kg daily 16. This aligns with the results of our study, with 98% of patients receiving a daily dose of 2mg/kg. The mean length of propranolol treatment was about 11 months and 97% of patients responded to propranolol with 80% having a nearly complete or complete response to an initial treatment cycle. Surgical interventions for IH include resection or ablation with laser17 . Seven percent of patients in our study received laser treatment with PDL or neodymium yttrium aluminum garnet (Nd:YAG), and 10% received surgical excision in addition to propranolol treatment. While the introduction of propranolol has decreased the need for surgical excisions for IH, surgical intervention may still be indicated in cases of ulceration, parent preference, patients with late presentation, and patients with sequelae after IH involution18.
Regrowth after discontinuation of propranolol therapy occurs in as many as 10-15% of patients 19 in some reports. Previous studies have investigated the predictive factors for IH recurrence and have found that most cases were due to partial regression, meaning that recurrent lesions likely originate from the residual hemangioma cells3,20. Our study demonstrates similar findings with almost 60% of patients requiring a second round of propranolol after having a partial lesion regression response to initial propranolol treatment. Additionally, the length of initial propranolol treatment for the 14 patients requiring a second cycle was 8 months compared to 11 months in the entire cohort. Previous studies have recommended prolonged monitoring of facial IH after initial propranolol treatment termination to detect regrowth 21. Additionally, proliferation of residual lesions is likelier when propranolol therapy is ended at earlier stages compared to later stages, which is a plausible explanation for our study results 19,22.
One interesting consideration our study proposes is a familial history of hemangiomas or cardiac abnormalities as a risk factor for necessitating a second propranolol cycle. A known risk factor for the development of IH includes a family history of IH. Additionally, previous studies have identified a higher frequency of cardiac abnormalities among patients with IH in respect to the general population. However, the correlation of these risk factors with the need for a subsequent propranolol cycle remains novel. It is important to acknowledge that the significance of these findings is limited by the relatively small number of patients necessitating a second round of propranolol therapy. Further exploration with larger cohorts is essential to validate and fully understand the implications of these potential risk factors in guiding treatment strategies for IH recurrence.
The primary limitation of our study is its retrospective design, as there may have been missing or unreported data. A larger patient cohort and a multi-institutional approach are imperative for future investigations to corroborate these findings. Additionally, the prominence of head/face hemangiomas might be influenced by referral biases inherent in a tertiary center setting.