Clinical Features, Prognostic Factors, and Treatment Interventions for Ulceration in Patients With Infantile Hemangioma

Abstract

IMPORTANCEUlceration is a common complication of infantile hemangioma (IH), which leads to substantial morbidity. Ulceration in IH has not been systematically studied since the advent of β-blocker therapy for IH. OBJECTIVESTo examine treatment interventions used for ulceration in IH and identify clinical prognostic indicators of healing time. DESIGN, SETTING, AND PARTICIPANTS A retrospective, multicenter cohort study was conducted on 436 consecutive patients with a clinical diagnosis of ulcerated IH and available clinical photographs. Patients receiving care at tertiary referral centers evaluated between 2012 and 2016 were included; statistical and data analysis were performed from February 7 to April 27, 2020. EXPOSURES Clinical characteristics, treatment interventions, course, complications, and resource use were analyzed. Treatment interventions for ulceration in IH included local (wound care, topical), systemic (β-blocker, corticosteroids), and procedural (pulsed-dye laser). MAIN OUTCOMES AND MEASURES The primary end point was time to complete or nearly complete ulceration healing. Clinical characteristics were analyzed to determine the responses to most common interventions and prognostic factors for healing of ulceration. RESULTSOf the 436 patients included in the study, 327 were girls (75.0%); median age at ulceration was 13.7 weeks (interquartile range, 8.86-21.30 weeks). The median heal time was 4.79 weeks (95% CI, 3.71-5.86 weeks) with wound care alone, 5.14 weeks (95% CI, 4.57-6.00 weeks) with timolol, 6.36 weeks (95% CI, 5.57-8.00 weeks) with a systemic β-blocker, and 7.71 weeks (95% CI, 6.71-10.14 weeks) with multimodal therapy. After adjusting for IH size, a dose of propranolol less than or equal to 1 mg/kg/d was associated with shorter healing time compared with higher propranolol doses (hazard ratio, 2.04; 95% CI, 1.11 to 3.73; P = .02). Size of the IH was identified as a significant prognostic factor for healing time in multivariable analysis. Increasing size of IH portends a proportionately longer time to heal of the ulceration.CONCLUSIONS AND RELEVANCE Despite the use of β-blockers, this cohort study found that a subset of patients with IH ulceration continued to experience prolonged IH healing times. Larger IH size appears to be a poor prognostic factor for time to heal. For patients requiring systemic therapy, initiation of propranolol at lower doses (Յ1 mg/kg/d) should be considered.

Worsening ulceration of infantile hemangioma after initiation or escalation of propranolol

“…In a 2013 study evaluating propranolol use to treat IH in PHACE syndrome, three patients showed similar worsening ulceration of IH, 10 as described here. Recently, Fernandez Faith et al's multicenter retrospective cohort study found that lower‐dose propranolol therapy (<1 mg/kg/day) demonstrated a trend to faster healing time of ulcerated IH compared with standard propranolol doses 15 . Of note, in their findings, a fifth of ulcerated IHs developed after active treatment (including, but not limited to propranolol).…”

Immediate possible adverse event rates in infants treated with oral propranolol for infantile haemangiomas at an Australian urban tertiary hospital between 2016 and 2019

“…The previously mentioned European expert consensus group recommended dosage starting at 1 mg/kg/day in either inpatient or outpatient settings, 28 increasing to a goal dosage of 2–3 mg/kg/day if required 25 . A recent study has found lower doses of propranolol ≤1 mg/kg/day have been associated with shorter healing times 21 …”

Advanced nanocarrier- and microneedle-based transdermal drug delivery strategies for skin diseases treatment

“…Beta-blockers (e.g., propranolol ointment, timolol cream, etc .) 182 , glucocorticoids, bleomycin, rapamycin, and other antitumor drugs can be employed.…”