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Objectives To identify clinical factors associated with complications of periocular infantile hemangioma (IH) and monitor improvement in complication rates post-treatment. Methods Retrospective cohort study. Eighty-nine patients diagnosed with periocular IH at a pediatric dermatology clinic of a tertiary care center between 2001 and 2013 were included with parental approval. Parents were interviewed by telephone between July and September of 2015, then again in January 2018 to inquire about ophthalmologic follow-up. Electronic medical records were reviewed from January 2001 through January 2018. Results Sixty percent of patients demonstrated ocular sequelae, including astigmatism (33%), visual axis obstruction (29%), nasolacrimal duct obstruction (7%), ptosis (4%), amblyopia (3%), and strabismus (1%). Compared with superficial IH, deep and mixed IH had higher odds, 3.4 (P = 0.025) and 3.8 (P = 0.034), respectively, of developing ocular sequelae. All patients with astigmatism prior to involution of IH received systemic therapy, with a significant post-treatment decrease in the proportion of patients with astigmatism (40% to 18%, P = 0.027). Three-quarters of patients experienced complete IH involution by time of enrollment in kindergarten. Fifty-one (57.3%) patients received formal ophthalmologic evaluation confirmed through chart review or phone interview, with average follow-up duration of 51.2 months (range: 1.9, 99.3). Conclusion Deep and mixed IH were more likely to demonstrate ocular complications than superficial IH. Rate of astigmatism decreased with systemic therapy. Our study suggests that patients with periocular IH have a lower rate of amblyopia now compared with the prepropranolol era and emphasizes the importance of early treatment of periocular IH to prevent permanent visual sequelae.

Carbon dioxide ablative fractional laser (CO2-AFL) therapy has not been widely adopted in pediatric burn care given limited outcomes literature and no established guidelines on laser treatment protocols. We present our experience to further elucidate the clinical role of CO2-AFL therapy for pediatric hypertrophic burn scars. We conducted a prospective cohort study of pediatric burn patients undergoing CO2-AFL treatment of hypertrophic, symptomatic burn scars at a tertiary care regional burn center during a 2-year period. Scars were assessed before each treatment using the Patient and Observer Scar Assessment Scale (POSAS), a validated, subjective, comprehensive scar assessment tool. We treated 49 pediatric patients for a total of 180 laser sessions. Burn severity was full thickness (63.6%) or deep partial thickness (47.7%). Observer-rated POSAS scores revealed statistically significant improvements in pigment, thickness, relief, pliability, and surface area after one treatment with continued improvement until the last laser session. Patient-rated POSAS revealed statistically significant improvements in color, stiffness, thickness, and irregularity after laser treatments. Total POSAS improved from 89.6 ± 17.5 to 76.6 ± 16.8 (P < .0001) after one treatment with further improvement to 69.2 ± 14.9 (P < .0001) at the final laser session. We found convincing evidence that CO2-AFL therapy improves hypertrophic burn scars on both patient- and observer-rated scales confirming statistical and clinical significance to both providers and families. These findings demonstrate that CO2-AFL can improve hypertrophic burn scars in pediatric patients providing a lower risk alternative to invasive therapies and a more immediate, efficacious alternative to more conservative scar treatments.

Importance Oral propranolol is widely considered to be first-line therapy for complicated infantile hemangioma, but its use in patients with PHACE (posterior fossa malformations, hemangioma, arterial anomalies, cardiac defects, eye anomalies) syndrome has been debated owing to concerns that the cardiovascular effects of the drug may increase the risk for arterial ischemic stroke. Objective To assess the incidence of adverse events among patients with PHACE syndrome receiving oral propranolol for infantile hemangioma. Design, Setting, and Participants This multicenter retrospective cohort study assessed the incidence of adverse events among 76 patients with PHACE syndrome receiving oral propranolol for infantile hemangioma at 11 tertiary care, academic pediatric dermatology practices. Medical records from January 1, 2010, through April 25, 2017, were reviewed. Exposures Patients received oral propranolol, 0.3 mg/kg/dose or more. Main Outcomes and Measures The main outcome was the rate and severity of adverse events occurring throughout the course of treatment with oral propranolol, as documented in the medical records. Adverse events were graded from 1 to 5 using a scale derived from the Common Terminology Criteria for Adverse Events and were considered to be serious if they were grade 3 or higher. Results A total of 76 patients (59 girls and 17 boys; median age at propranolol initiation, 56 days [range, 0-396 days]) met the inclusion criteria. There were no reports of serious adverse events (ie, stroke, transient ischemic attack, or cardiovascular events) during treatment with oral propranolol. A total of 46 nonserious adverse events were reported among 29 patients (38.2%); the most commonly reported nonserious adverse events were sleep disturbances and minor gastrointestinal tract and respiratory tract symptoms. In a comparison with 726 infants who received oral propranolol for hemangioma but did not meet criteria for PHACE syndrome, there was no significant difference in the rate of serious adverse events experienced during treatment (0 of 76 patients with PHACE syndrome and 3 of 726 patients without PHACE syndrome [0.4%]). Conclusions and Relevance This study found that oral propranolol was used to treat infantile hemangioma in 76 patients with PHACE syndrome and that no serious adverse events were experienced. These data provide support for the safety of oral propranolol in this patient population.

Background Initial propranolol recommendations for infantile hemangioma published in 2013 were intended as provisional best practices to be updated as evidence-based data emerged. Methods A retrospective multicenter study was performed to evaluate utility of prolonged monitoring after first propranolol dose and escalation(s). Inclusion criteria included diagnosis of hemangioma requiring propranolol of greater than or equal to 0.3 mg/kg per dose, younger than 2 years, and heart rate monitoring for greater than or equal to 1 hour. Data collected included demographics, dose, vital signs, and adverse events. Results A total of 783 subjects met inclusion criteria; median age at initiation was 112 days. None of the 1148 episodes of prolonged monitoring warranted immediate intervention or drug discontinuation. No symptomatic bradycardia or hypotension occurred during monitoring. Mean heart rate change from baseline to 1 hour was –8.19/min (±15.54/min) and baseline to 2 hours was –9.24/min (±15.84/min). Three preterm subjects had dose adjustments because of prescriber concerns about asymptomatic vital sign changes. No significant difference existed in pretreatment heart rate or in heart rate change between individuals with later adverse events during treatment and those without. Conclusion Prolonged monitoring for initiation and escalation of oral propranolol rarely changed management and did not predict future adverse events. Few serious adverse events occurred during therapy; none were cardiovascular.

Background/objectives First-line therapy for infantile hemangiomas (IH) is oral propranolol, a systemic beta-blocker with the risk of rare but serious adverse effects. Topical timolol presents an attractive off-label alternative with good tolerability, but sequential therapy with propranolol followed by timolol is not well studied. Here, we report effects of topical timolol preceding or following oral propranolol as adjunct therapy for IH. Methods A retrospective chart review of 559 patients with IH seen at the pediatric dermatology clinic of a tertiary care center between December 2008 and January 2018. Children were grouped by treatment received: propranolol only, timolol only, propranolol to timolol, timolol to propranolol to timolol, and timolol to propranolol. Patient demographics, clinical/treatment characteristics, and pairwise differences were explored between groups. Results Among all patients treated with propranolol, those who received propranolol followed by timolol received the shortest duration of oral propranolol and were the youngest at the time of propranolol completion. These patients received propranolol for a median of 2.2 months duration (P = 0.006) and were a median of 1.7 months younger (P = 0.007) compared with patients who received oral propranolol only. None had treatment failure defined as requiring propranolol reinitiation, compared with 13% of patients in the propranolol only group (P = 0.036). Conclusions Sequential therapy with oral propranolol followed by topical timolol for IH may help minimize potential adverse effects of systemic beta-blockers by reducing the duration of propranolol therapy and facilitating successful taper at a younger age without an increase in treatment failures.

Background Arteriovenous malformations (AVMs) are high flow vascular anomalies that are difficult to manage given their high recurrence rate. At this time, the optimal treatment of AVMs involves embolization and surgical resection. However, few studies have examined patient outcomes after a delayed surgical resection approach. Methods A retrospective chart review of all patients presenting to a single institution with vascular malformations from 2000 to 2016 was performed. Patients with facial AVMs that underwent operative management were included. Records were reviewed for patient characteristics, lesion natural history, operative timing after embolization ( 72 hours), and outcomes. Results 11 patients fulfilled the inclusion/exclusion criteria. Nine patients were female, with an average age at resection of 29.1 years. Three patients had hemi/mid-facial AVMs, 1 patient had a nasal AVM, 3 patients had labial AVMs, 1 patient had an AVM on the chin, and 1 had a periorbital AVM. Average time between embolization and primary resection was 8.6 days (range 1-24). No complications requiring reoperation occurred in any patient. Average follow-up was 32.6 months, with 2 recurrences at a mean of 47.6 months. Timing of resection, Schobinger stage, and resection completeness did not significantly affect recurrence (P >0.05). Lesion size >6 cm in any dimension was significantly associated with recurrence (P = 0.018). Conclusion Compared to early resection, delayed (>72 h) surgical resection after embolization of facial AVMs is a viable treatment option and results in non-inferior recurrence rates (25 vs 14% respectively over a 40-month period).

IMPORTANCE: Patients with somatic overgrowth commonly require surgical intervention to preserve function and improve cosmesis. To our knowledge no observation of scarring outcomes in this population has been published to date. OBJECTIVE: To observe the frequency of abnormal scarring in patients with somatic overgrowth and sequencing-verified mutations in the PIK3CA gene. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study evaluated scarring outcomes in patients with PIK3CA-related overgrowth. Samples of affected tissue were sequenced between July 2015 and October 2016. Medical records from multiple large academic tertiary care centers were reviewed for surgical history and scar descriptions, and clinical photographs were assessed by 2 surgeons (J.N.J. and D.M.K.) to confirm abnormal scarring. Analysis of medical records and photographs was performed between April 2017 and June 2017 by a multidisciplinary team from dermatology, plastic surgery, orthopedic surgery, radiology, and genetics departments. All patients considered for the study were diagnosed with somatic overgrowth and previously had affected tissue sent for next-generation sequencing. Those with pathogenic PIK3CA variants and 1 or more prior surgical procedures were reviewed. MAIN OUTCOMES AND MEASURES: Presence of excessive scarring in patients with PIK3CA overgrowth. RESULTS: A total of 57 patients with segmental overgrowth syndromes were sequenced. Of the 57 patients, 25 (44%) had pathogenic or likely pathogenic variants in PIK3CA. Of those with pathogenic PIK3CA variants, 6 (24%) had past surgical procedures, all with preoperative and postoperative photographs. Of 6 patients with PIK3CA-related overgrowth and a history of 1 or more surgical procedure, 4 (67%) developed excessive scarring. The cohort with abnormal scarring comprised 3 females and 1 male, with a median age of 8.5 years. All abnormal scarring occurred in affected overgrowth tissue. Three of the 4 patients developed the excessive scarring after debulking procedures for overgrowth and/or vascular malformations of the upper or lower extremity. CONCLUSIONS AND RELEVANCE: Excessive scarring occurred frequently in patients with PIK3CA-related overgrowth syndromes. The risk of abnormal scarring should therefore be discussed preoperatively. Given the activating nature of these PIK3CA variants, we suggest that the excessive scarring may be owing in part to up-regulation of the PI3K-Akt-mTOR pathway. Additional studies are needed to assess scarring outcomes in patients with other types of overgrowth.

Classification of vascular anomalies (VAs) is challenging due to overlapping clinical symptoms, confusing terminology in the literature and unfamiliarity with this complex entity. It is important to recognize that VAs include two distinct entities, vascular tumours (VTs) and vascular malformations (VaMs). In this article, we describe SE Mitchell Vascular Anomalies Flow Chart (SEMVAFC), which arises from a multidisciplinary approach that incorporates clinical symptoms, physical examination and magnetic resonance imaging (MRI) findings to establish International Society for the Study of Vascular Anomalies (ISSVA)-based classification of the VAs. SEMVAFC provides a clear visual pathway for physicians to accurately diagnose Vas, which is important as treatment, management, and prognosis differ between VTs and VaMs.

Objectives: We sought to determine the effect of propranolol on cardiovascular and blood glucose parameters in infants with symptomatic infantile hemangiomas who were hospitalized for initiation of treatment, and to analyze adverse effects of propranolol throughout the course of inpatient and outpatient treatment. Methods: A retrospective cohort analysis was performed on 50 infants (age less than 12 months) with symptomatic infantile hemangiomas who were hospitalized for propranolol initiation between 2008 and 2012. Demographic data and disease characteristics were recorded. Systolic and diastolic blood pressures, heart rate, blood glucose values, and adverse events recorded during hospitalization were analyzed. An additional cohort of 200 consecutively treated children was also assessed for adverse events associated with outpatient propranolol use. Results: The median age among the inpatient cohort was 3.4 months (range, 0.8 to 12.0 months). Infants older than 6 months were more likely to exhibit bradycardia than were younger infants (p < 0.001). Hypotensive and/or bradycardic periods were infrequent and were not associated with observable clinical symptoms. The mean systolic and diastolic blood pressures and the mean heart rate decreased significantly from day 1 of hospitalization to day 2 (p = 0.004; p = 0.008; p < 0.001), but not from day 2 to day 3, when the propranolol dose was increased to target. Hypoglycemia was rare (0.3% incidence.) Among the 250 outpatients, 2 infants developed lethargy and hypoglycemia during a viral illness and recovered without sequelae. One infant experienced recurrent bronchospasm with viral illnesses and required concomitant bronchodilator therapy. Conclusions: Frequent deviations from normal ranges of blood pressure and heart rate occur upon initiation of propranolol, but are clinically asymptomatic. These findings support that outpatient initiation of propranolol in healthy, normotensive infants appears to be a relatively safe alternative to inpatient initiation. Hypoglycemia is rare, but can occur throughout the treatment period; parent counseling is of paramount importance.

BACKGROUND/OBJECTIVES Nasal infantile hemangiomas (IHs) pose serious medical complications and psychosocial stress if tumor involution is incomplete or prolonged. The objective was to determine which IH characteristics are associated with complications and are predictive of outcome, assessed as the presence of IHs or residual skin changes upon kindergarten entry, to better manage these lesions and counsel families. METHODS A retrospective chart review of all patients seen in the Division of Pediatric Dermatology at Johns Hopkins Medicine between 2001 and 2014 for nasal IHs (N = 89) was performed. A follow-up telephone interview with parents was conducted in June and July 2014. RESULTS Complications were observed in 39% of patients. Segmental and indeterminate IHs were more likely to have complications than focal IHs (p = 0.01). Mixed IHs were more likely to ulcerate than deep or superficial IHs (p = 0.01). Eighty percent of patients had treatment and 19% had surgery. Although IHs regressed by kindergarten entry in 70% of patients, 78% of these patients had residual skin changes. Mixed and superficial IHs left more residua than deep IHs (p = 0.04). A statistical comparison of treatments with respect to outcome at kindergarten entry could not be made because subgroups were too small and heterogeneous. CONCLUSION Nasal IHs had higher rates of complications and treatment than previous reports of IHs at all body sites. Lesions of segmental and indeterminate type and mixed depth should be identified as high risk and treated accordingly. Parents may be counseled that most nasal IHs involute by kindergarten but leave residua and that early referral for treatment may be important for the best outcome.

BACKGROUND: There has been a dramatic increase in the off-label use of ophthalmic timolol maleate, a β-blocker used for infantile hemangioma (IH) treatment as a topical counterpart to oral propranolol. Its safety and efficacy in a pediatric population with IH have not been evaluated in a large cohort. Our goal was to retrospectively assess timolol’s effectiveness, discern characteristics associated with response, and document reported adverse events. METHODS: A multicenter retrospective cohort study of 731 patients treated with topical timolol was completed at 9 centers. Inclusion required an IH suitable for timolol in the treating physician’s judgment and access to clinical details including photographs. Logistic regression analysis and descriptive statistics were performed. Primary outcome measures were efficacy assessed by using visual analog scales for color and for size, extent, and volume from review of digital photographs taken as standard of care. RESULTS: Most IHs were localized (80.1%) and superficial (55.3%). Risk of disfigurement was the most common indication for therapy (74.3%). Duration of therapy (P < .0001), initial thinness (P = .008), and subtype (P = .031) were significant predictors of response. Best response occurred in superficial IHs CONCLUSIONS: Timolol seems to be a well-tolerated, safe treatment option with moderate to good effectiveness, demonstrating best response in thin, superficial IHs regardless of pretreatment size. Timolol can be recommended as an alternative to systemic β-blockers and watchful waiting for many patients.

Infantile hepatic hemangioma is the most common benign liver tumor during infancy. Prompt diagnosis and timely institution of therapy are of utmost importance. Magnetic resonance imaging (MRI) plays a key role in the correct diagnosis and monitoring of treatment. We report on a 15-week-old girl with multifocal infantile hemangiomas of the liver and high output congestive heart failure. Diagnosis was confirmed by MRI. Subsequent treatment with propranolol and steroids showed dramatic regression of the lesions within 24 weeks. We present the characteristic MRI findings and discuss treatment options together with a comprehensive review of the relevant literature. Conclusion Propranolol appears highly efficacious in the management of infantile hepatic hemangioma; dedicated MRI is essential in confirming the diagnosis and monitoring of treatment.

Xeroderma pigmentosum (XP) is a rare autosomal recessive defect in DNA endonuclease activity that is associated with the development of cutaneous malignancies, at sun exposed sites, including basal cell carcinoma, squamous cell carcinoma, and melanoma. Squamous cell carcinomas are also known to target the anterior tongue. Patients sometimes develop angiosarcomas, and these invariably arise from sun-exposed skin. A biopsy was taken from a large mass arising in the anterior tongue of an 11-year-old girl with XP and a history of cutaneous basal cell carcinomas. The histopathologic findings demonstrated a high grade epithelioid neoplasm resembling a poorly differentiated squamous cell carcinoma, but the immunohistochemical profile (AE1/AE3 negative, p63 negative, CD31 positive, CD34 positive) established the diagnosis of angiosarcoma. Angiosarcoma is an XP-related tumor that usually arises in sun-exposed skin but can also arise in the oral cavity. For patients with XP who develop epithelioid neoplasms of the oral cavity, epithelioid angiosarcoma should be considered in the differential diagnosis.

Bullous systemic lupus erythematosus is a subepidermal blistering disease that occurs only rarely in a subset of patients with systemic lupus erythematosus and even less commonly in pediatric patients. Autoimmunity in bullous systemic lupus erythematosus is characterized by the presence of circulating anti-type VII collagen antibodies. We report here a case of a child whose initial systemic lupus erythematosus presentation was a diffuse bullous eruption.

Importance While propranolol is touted as superior to prednisolone for treating infantile hemangiomas (IH), a randomized clinical trial (RCT) comparing the outcome and tolerability of these medications for symptomatic, proliferating IH has not been reported. Objectives To determine if oral propranolol is more efficacious and better tolerated than prednisolone in treating symptomatic, proliferating IH and to determine the feasibility of conducting a multi-institutional, RCT comparing efficacy and tolerability of both medications. Design, Setting, and Participants Phase 2, investigator-blinded, multi-institutional RCT conducted in 3 academic vascular anomalies clinics on 19 of 44 eligible infants aged between 2 weeks and 6 months. All participating patients had symptomatic proliferating IH treated between September 1, 2010, and August 1, 2012. Interventions Treatment with oral propranolol vs prednisolone (2.0 mg/kg/d) until halted owing to toxic effects or clinical response. Main Outcomes and Measures Primary outcome was change in IH size after 4 months of therapy. Secondary outcomes were response rate and frequency and severity of adverse events (AEs). Results The primary outcome showed no difference in lesion size or affected skin area after 4 months of therapy: 41% and 1.32 mm 2 for prednisolone vs 64% and 0.55 mm 2 for propranolol ( P = .12 for lesion size, and P = .56 for affected skin area). Longitudinal analyses showed a faster response in total lesion outer dimension with prednisolone ( P = .03), but this advantage over time was not noted when central clearing and outer dimension were included in the analysis ( P = .91). The overall frequency of AEs was similar (44 for prednisolone vs 32 for propranolol) ( P = .84), but prednisolone-treated participants had more grade 3 severe AEs (11 vs 1) ( P = .01), particularly growth retardation resulting in size and weight below the fifth percentile. Early study withdrawal owing to AEs occurred in 6 (75%) of 8 patients in the prednisolone group but 0 of 11 propranolol-treated participants. The mean duration of therapy was shorter for prednisolone (141 vs 265 days), reflecting the higher rate of early withdrawals. Conclusions and Relevance Both medications show similar efficacy for reducing the area of symptomatic, proliferating IH. Although prednisolone showed a faster response rate, propranolol was better tolerated with significantly fewer severe AEs. Propranolol should be the first line of therapy for symptomatic IH unless contraindicated or unless future studies demonstrate severe AEs from propranolol. Recruiting participants for a phase 3 RCT would be difficult owing to safety profiles measured here and emerging trends favoring propranolol. Trial Registration clinicaltrials.gov Identifier:NCT00967226