Multicenter Study of Long-Term Outcomes and Quality of Life in PHACE Syndrome after Age 10.

OBJECTIVE: To characterize long-term outcomes of PHACE syndrome. STUDY DESIGN: Multicenter study with cross-sectional interviews and chart review of individuals with definite PHACE syndrome ≥10 years of age. Data from charts were collected across multiple PHACE-related topics. Data not available in charts were collected from patients directly. Likert scales were used to assess the impact of specific findings. Patient-Reported Outcomes Measurement Information System (PROMIS) scales were used to assess quality of life domains. RESULTS: A total of 104/153 (68%) individuals contacted participated in the study at a median of 14 years of age (range 10-77 years). There were infantile hemangioma (IH) residua in 94.1%. Approximately one-half had received laser treatment for residual IH, and the majority (89.5%) of participants were satisfied or very satisfied with the appearance. Neurocognitive manifestations were common including headaches/migraines (72.1%), participant-reported learning differences (45.1%), and need for individualized education plans (39.4%). Cerebrovascular arteriopathy was present in 91.3%, with progression identified in 20/68 (29.4%) of those with available follow-up imaging reports. Among these, 6/68 (8.8%) developed moyamoya vasculopathy or progressive stenoocclusion, leading to isolated circulation at or above the level of the circle of Willis. Despite the prevalence of cerebrovascular arteriopathy, the proportion of those with ischemic stroke was low (2/104; 1.9%). PROMIS global health scores were lower than population norms by at least 1 SD. CONCLUSIONS: PHACE syndrome is associated with long-term, mild to severe morbidities including IH residua, headaches, learning differences, and progressive arteriopathy. Primary and specialty follow-up care is critical for PHACE patients into adulthood.

Delphi Consensus on Diagnostic Criteria for LUMBAR Syndrome.

OBJECTIVE: To develop consensus on diagnostic criteria for LUMBAR syndrome, the association of segmental infantile hemangiomas that affect the Lower body with Urogenital anomalies, Ulceration, spinal cord Malformations, Bony defects, Anorectal malformations, Arterial anomalies and/or Renal anomalies. STUDY DESIGN: These diagnostic criteria were developed by an expert multidisciplinary and multi-institutional team based on analysis of peer-reviewed data, followed by electronic-Delphi consensus of a panel of 61 international pediatric specialists. RESULTS: After 2 Delphi rounds, a 92% or higher level of agreement was reached for each Delphi statement. 98% of panelists agreed with the diagnostic criteria, and 100% agreed the criteria would be useful in clinical practice. The diagnosis of LUMBAR requires the presence of a segmental, or patterned, infantile hemangioma of the lumbosacral, sacrococcygeal, or pelvic cutaneous regions plus one additional criterion of the urogenital, spinal, bony, anorectal, arterial, or renal organ systems. CONCLUSIONS: These diagnostic criteria will enhance clinical care by improving screening, detection, and overall awareness of this poorly understood neurocutaneous disorder. The criteria can be utilized by a wide variety of pediatric subspecialists. In addition, formal criteria will improve phenotypic uniformity among LUMBAR syndrome cohorts and a patient registry, allowing investigators to assess clinical features, long-term outcomes, and results of genetic sequencing in a standardized manner. Finally, these criteria will serve as a starting point for prospective studies to establish formal screening and management guidelines.

ALKBH5 facilitates the progression of infantile hemangioma by increasing FOXF1 expression in a m6A-YTHDF2 dependent manner to activate HK-2 signaling.

Alkylation repair homolog protein 5 (ALKBH5) is reported to participate in infantile hemangioma (IH) progression. However, the underlying mechanism of ALKBH5 in IH remains unclear. Using qRT-PCR and Western blotting, ALKBH5, forkhead box F1 (FOXF1) and hexokinase 2 (HK-2) expressions in IH tissues and IH-derived endothelial cells XPTS-1 were assessed. The Me-RIP assay was used to analyze FOXF1 m6A level. CCK8, colony formation, flow cytometry and transwell assays were employed to determine IH cell viability, proliferation, apoptosis, migration and invasion. The interactions between YTH (YT521-B homology) domain 2 (YTHDF2), FOXF1 and HK-2 were analyzed by RIP, dual luciferase reporter gene assay and/or ChIP assay. The in vivo IH growth was evaluated in immunocompromised mice. FOXF1 was overexpressed in IH tissues, and its silencing inhibited IH cell proliferation, migration and invasion whereas promoting cell apoptosis in vitro. ALKBH5 upregulation facilitated FOXF1 mRNA stability and expression in IH cells in a m6A-YTHDF2-dependent manner. FOXF1 downregulation reversed the impact of ALKBH5 upregulation on IH cellular phenotypes. It also turned out that FOXF1 positively regulated HK-2 expression in IH cells through interacting with the HK-2 promoter. HK-2 upregulation abolished FOXF1 knockdown's inhibition on IH cell aggressive behaviors. ALKBH5 or FOXF1 silencing suppressed IH tumor development via HK-2 signaling in immunocompromised mice. ALKBH5 promoted FOXF1 expression m6A-YTHDF2 dependently, which in turn elevated HK-2 expression, thereby accelerating IH development.

OTUB1 Catalytic-Independently Deubiquitinates TGFBI and Mediates the Angiogenesis in Infantile Hemangioma by Regulating Glycolysis.

BACKGROUND: Infantile hemangioma (IH) arises as a result of dysregulation of both angiogenesis and vasculogenesis. The deubiquitylase OTUB1 (OTU domain, ubiquitin aldehyde binding 1) has been reported to play an essential role in multiple cancers; however, its function in the progression of IH and the underlying mechanisms regulating angiogenesis remain unclear. METHODS: Transwell assays, EdU assays, and tube formation assays were performed to investigate the biological behavior of IH in vitro. IH animal models were established to estimate the progression of IH in vivo. Mass spectrometric analysis were conducted to detect the downstream of OTUB1 and ubiquitination sites of transforming growth factor beta induced (TGFBI). Half-life assays and ubiquitination test were performed to investigate the interaction between TGFBI and OTUB1. Extracellular acidification rate assays were employed to estimate the glycolysis level in IH. RESULTS: The expression of OTUB1 was obviously increased in proliferating IH as compared to the involuting and involuted IH tissues. Through in vitro experiments, the knockdown of OTUB1 inhibited the proliferation, migration and tube formation of human hemangioma endothelial cells, while the overexpression of OTUB1 promoted the proliferation, migration and angiogenic abilities of human hemangioma endothelial cells. The knockdown of OTUB1 significantly suppressed IH progression in vivo. Furthermore, TGFBI was predicted as a functional downstream target of OTUB1 in IH by mass spectrometry. Mechanistically, OTUB1 interacted with and deubiquitylated TGFBI on the K22 and K25 residues, which was demonstrated to be independent of the catalytic activity of OTUB1. The inhibitory effects of OTUB1 knockdown on cell proliferation, migration and tube formation ability of human hemangioma endothelial cells were reversed by TGFBI overexpression. Further, we found that OTUB1 mediated glycolysis by regulating TGFBI in infantile hemangioma. CONCLUSIONS: OTUB1 deubiquitinates TGFBI in a catalytic-independent manner and promotes angiogenesis in infantile hemangioma by regulating glycolysis. Targeting OTUB1 might be an effective therapeutic strategy for inhibiting IH progression and tumor angiogenesis.

Serum apelin as a potential biomarker for infantile hemangiomas.

BACKGROUND: Infantile hemangiomas (IHs) are common benign vascular tumors in infants. Apelin, an endogenous cytokine, is implicated in the angiogenesis of neoplastic diseases. We aimed to explore the association between apelin and IHs, providing a foundation for clinical applications. METHODS: We identified differential expression of apelin in proliferative IHs compared to healthy controls (HCs) through bioinformatics analysis of publicly available databases and verified by Immunofluorescence. Enzyme-linked immunosorbent assay was used to quantify the serum levels of apelin and vascular endothelial growth factor (VEGF) in a cohort of 116 cases of proliferative IHs, 65 cases of capillary malformations (CMs), and 70 HCs. RESULTS: Apelin and APJ (APLNR, apelin receptor) were identified as the significantly upregulated differentially expressed genes (DEGs) in proliferative IHs. Immunofluorescence staining indicated high expression of apelin in proliferative IHs, while minimal expression in non-IH lesions. Apelin in IHs was reduced following 6 months of propranolol treatment. Serum apelin levels were significantly higher in the IH group compared to both the CM and HC groups. Moreover, apelin exhibited excellent discriminatory ability in distinguishing IHs from HCs, with an area under the curve (AUC) exceeding 0.90. A positive correlation was observed between the levels of apelin and the size of superficial IHs. The expression profiles of VEGF and apelin in IHs were found to be consistent. CONCLUSIONS: Apelin shows promise as a potential biomarker for IHs. The association between apelin and IH size, as well as its responsiveness to propranolol treatment, indicates its possible utility as a valuable indicator for the therapeutic evaluation of IHs.

Exploration of the optimal time to discontinue propranolol treatment in infantile hemangiomas: A prospective study.

BACKGROUND: Relapse of infantile hemangiomas after withdrawal from propranolol treatment is common. Early withdrawal is believed to increase the risk of relapse. OBJECTIVE: The objective of this study was to determine the optimal time to discontinue propranolol treatment for infantile hemangiomas. METHODS: A prospective study conducted at a tertiary referral center. RESULTS: Compared to withdrawal after 1-month maintenance treatment, withdrawal after 3-month maintenance, corresponding achieving maximum regression of infantile hemangiomas, was associated with a lower major relapse rate (P = .041). The relapse (P = .055) and adverse event rates (P = .154) between the 2 withdrawal modes were not statistically significant. Compared with direct withdrawal, the relapse (P = .396), major relapse (P = .963), and adverse event rates (P = .458) of gradual withdrawal were not statistically different. Patients with/without relapse could be best distinguished according to whether withdrawal followed a 3-month maintenance and age >13 months (area under the receiver operating characteristic curve = 0.603). Patients with/without major relapse could be best distinguished according to whether withdrawal was accompanied by 3-month maintenance (area under the receiver operating characteristic curve = 0.610). LIMITATIONS: The limitations of this study are nonrandomization and single-center design. CONCLUSIONS: The optimal propranolol withdrawal time to avoid relapse is when the patient is aged >13 months and the lesion has maintained for 3 months after reaching maximum regression, while the optimal time to prevent major relapse is after 3 months of maintenance.

Infantile hemangioma in a subadult Chinese pangolin: a case report.

BACKGROUND: Hemangiomas are a relatively common type of tumor in humans and animals. Various subtypes of hemangiomas have been described in the literature. The classification methods for hemangiomas differ between human and veterinary medicine, and the basis for tumor classification can be found in the literature. CASE PRESENTATION: This study describes a tumor in the subcutaneous tissue of the right dorsum of an artificially rescued juvenile Chinese pangolin. Computed tomography (CT) examination yielded the preliminary diagnosis of a vascular malformation, and surgery was performed to resect the tumor. Histopathological examination showed that the tumor mainly was consisted of adipose tissue, capillaries, and spindle cells in the fibrous stroma. Immunohistochemistry showed the positive expression of CD31, CD34, α-SMA, GLUT1 and WT-1 in the tumor tissue, and the tumor was eventually diagnosed as an infantile haemangioma. CONCLUSION: The final diagnosis of infantile hemangioma was depended on the histopathological immunohistochemical and CT examination of the neoplastic tissue. This is the first report of infantile hemangioma in a critically endangered species Chinese pangolin.

Infantile hemangiomas: a dermatologist's perspective.

Infantile hemangioma (IH), the most common vascular tumor in pediatrics, is thought to arise from aberrant stem cell responses to stimuli such as hypoxia. This review explores the diverse manifestations, complications, and management strategies for IH, emphasizing the importance of a multidisciplinary approach. The epidemiology and risk factors associated with IH, including connections to prematurity, low birth weight, and family background, are discussed. The intricate pathogenesis involving hemangioma stem cells, KIAA1429, hypoxia, and the renin-angiotensin system is examined. The natural history and clinical features, as well as extracutaneous involvements such as hepatic IH, PHACES syndrome, and LUMBAR syndrome, are detailed. Complications such as ulceration, functional impairment, hypothyroidism, and cosmetic concerns are highlighted. The differential diagnosis and diagnostic modalities, including colorimeters, high-frequency ultrasonography, and imaging techniques, are discussed. Management approaches, including the use of propranolol, atenolol, corticosteroids, alternative systemic treatments, topical therapy, laser therapy, and surgery, are comprehensively reviewed. The evolving landscape of IH management is underscored, with ongoing research exploring alternative treatments and individualized approaches based on IH characteristics.

Rare complication - skin atrophy - after systemic conservative therapy of infantile hemangioma.

BACKGROUND: Hemangiomas, also called infantile hemangiomas (IH) or hemangiomas of infancy are the most frequently seen benign vascular tumors of infancy. Different types of hemangiomas are described in the literature. The current approach is to assess the risk and, if needed, first line treatment is to initiate systemic propranolol. CASE PRESENTATION: A 3-month-old Caucasian female patient was brought as an outpatient. The main complaint was an infantile hemangioma in the facial area, which as per the parents' story appeared within a week of birth like a small reddish line and it rapidly grew. Systemic propranolol was proposed as a first-line treatment and the adverse effects were explained. The parents, afraid of the side effects, wanted to explore other possibilities such as topical timolol, however, since it had no effect, propranolol was initiated in the end. Hemangioma was completely reduced in size; however, a skin defect was detected. As per the dermatologist's counsel, topical cream was initiated. The skin defect was reduced but not fully healed. The child is still being monitored periodically. CONCLUSION: After successful treatment of hemangioma, we identified a skin defect, which was very similar to steroid-induced skin atrophy. However, we cannot attribute this to a single factor. The only thing that can be concluded is that the subject needs a thorough studying, since rate of infantile hemangioma is high, and pediatricians need a clear management strategy of how to approach skin atrophy after successfully treating the hemangioma itself.

Practical surgical technique using the SMISS approach for lip reduction in involuted lip infantile hemangiomas.

BACKGROUND: Lip infantile hemangiomas tend to show less volumetric regression and are more susceptible to visible sequelae in the involuted stage. Some of them still require surgical management after propranolol therapy. This study aimed to evaluate the efficacy and safety of the Stepwise, Multi-Incisional, and Single-Stage (SMISS) approach applied to lip reduction for those with involuted lip hemangiomas. METHODS: A retrospective review was performed to evaluate patients with lip hemangioma who received previous propranolol treatment and underwent the aforementioned procedure. Demographic characteristics, lesion morphology, and medical history were reviewed. The Visual Analog Scale was applied to assess the postoperative appearance. Complications within 12 months postoperatively were recorded. RESULTS: A total of 18 patients with lip hemangioma were eligible. All patients received oral propranolol therapy before surgery, with treatment duration ranging from 6.0 to 23.0 months. Their age at surgery ranged from 2.5 to 9.0 years. The median Visual Analog Scale scores were 8.0, ranging from 4.0 to 10.0. No severe complications were reported. CONCLUSIONS: This modified technique based on the SMISS approach has proven reliable and effective in improving the aesthetic outcome for involuted lip infantile hemangiomas. Practical surgical techniques still play an important part in the propranolol era.

Clinical characteristics of infantile haemangioma in twins: a retrospective study.

BACKGROUND: Infantile hemangioma is one of the most common benign soft tissue tumors in infants. The pathogenesis of infantile hemangioma remains unclear and twin studies regarding its incidence may help clarify disease pathogenesis. Thus, this study aimed to analyze the clinical characteristics of infantile hemangioma in twin patients and discuss its clinical incidence. METHODS: We retrospectively analyzed the data of 83 pairs of twins with infantile hemangioma admitted to the Guangdong Provincial Women and Children Hospital and Henan Provincial People's Hospital between May 2016 and May 2022. Thirty-one pairs of twins among whom both developed infantile hemangioma and 52 pairs of twins among whom only one twin was affected were included. Analysis was performed using the Spearman correlation. Additionally, we analyzed the influence of factors such as sex, twin zygosity, preterm birth, birth weight, and assisted reproduction on the clinical characteristics of twins. RESULTS: We observed that disease occurrence in both twins correlated with assisted reproduction (χ2 = 13. 102, P < 0.05) and preterm birth (χ2 = 36.523, P < 0.05). Twin zygosity (χ2 = 0.716, P > 0.05) and total birth weight of twins (t=-3.369, P > 0.05) were not correlated with infantile hemangioma. However, among twins, the ones with lesser birth weight were more likely to develop infantile hemangioma. CONCLUSIONS: The clinical characteristics of infantile hemangioma in twins were consistent with their epidemiological characteristics. Female sex, preterm birth, less birth weight, and assisted reproduction increased the probability of morbidity in both twins. Analysis of the characteristics of infantile hemangioma in twins may assist further research and clinical treatment.

Regimen for accelerated propranolol initial dosing (RAPID).

BACKGROUND: Infantile hemangiomas are common vascular tumors in children. Propranolol has proven effective in treating infantile hemangiomas and while generally safe, has potential risk for more serious side effects of hypoglycemia, hypotension, bradycardia, bronchospasm, and cardiovascular or respiratory compromise. Current prescribing guidelines recommend initiating propranolol doses at 1 mg/kg/day, with up-titration to 2 mg/kg/day. This study aims to compare the incidence of adverse events in infants and children treated with propranolol initiated at 1 mg/kg/day versus being initiated directly at 2 mg/kg/day. METHODS: A retrospective cohort study was conducted using medical records of patients receiving propranolol therapy for infantile hemangiomas between October 2018-March 2021 at the Children's Hospital of Philadelphia. Patients were categorized by initial propranolol dosage: 1 or 2 mg/kg/day. The primary outcome measures included parent-reported adverse events, hypotension (defined by the Pediatric Advanced Life Support criteria), and bradycardia (defined as <1st percentile for age) following propranolol initiation. RESULTS: Out of the 244 patients identified, 123 were initiated at the 1 mg/kg/day dose, and 121 at the 2 mg/kg/day dose. There was no significant difference in the incidence of adverse events between the two groups (p = .057). Additionally, among patients initiated at 2 mg/kg/day, there were no significant differences in the incidence of age-related or weight-related adverse events for those younger than 2 months or those in the 1st or 2nd quartile for weight (p = .53). CONCLUSION: Infants and children initiated at 2 mg/kg/day did not demonstrate an increased incidence of adverse events associated with propranolol compared to those initiated at 1 mg/kg/day. These findings provide clinical evidence for the practice of accelerated propranolol initiation dosing.

Basal cell carcinoma arising at the site of a previously irradiated infantile hemangioma.

We describe a case of a previously irradiated infantile hemangioma in a patient 1 year of age. At the age of 78, the patient presented with a pink, pearly plaque at the previously irradiated infantile hemangioma site and was found to have a nodular basal cell carcinoma. [Correction added on 30 August 2023, after first online publication: In the preceding sentence, patient age has been corrected in this version] This case highlights the rare, but long-term risks of radiation therapy for hemangiomas, but also presents an interesting historical vignette in dermatological treatments, with photographic documentation. It also represents the longest time interval between irradiation of an infantile hemangioma and the development of a basal cell skin cancer, 70 years in this case.

Large, ulcerated infantile hemangioma of the chest wall complicated by life-threatening hemorrhage: Case report and literature review.

While ulceration is one of the most common infantile hemangioma (IH) complications, severe bleeding is a rare consequence, with a paucity of patients reported. We report a 5-month-old girl with a very large, mixed, partial segmental IH of the upper chest wall who, despite medical intervention, developed severe ulceration and multiple episodes of life-threatening bleeding that ultimately led to hemorrhagic shock. Experience in our patient and a review of six previous reports shows that severe bleeding is a risk when ulceration extends directly into an arterial feeding vessel that is often visible clinically. Other potential predictors for severe bleeding include large to very large IH size with extension of the tumor into underlying structures, segmental or partial segmental patterning, mixed and bulky morphology, and white discoloration as a sign of impending or worsening ulceration.

An analysis of information about infantile hemangiomas on TikTok: A cross-sectional study.

The video app TikTok, a controversial platform, has increasingly been utilized for the dissemination of health-related topics. In this study, the quality of information on the top 50 most viewed TikTok videos on infantile hemangiomas (IHs) labeled #hemangioma was analyzed. The results showed that the videos were skewed toward more severe subtypes of IH, and most were directed at raising awareness about IH or combating stigmatizing attitudes toward birthmarks. Providers should be aware that social media applications such as TikTok are a commonly used venue for parents to cope and connect but may relay inaccurate or misleading information.

The burden of treatment of propranolol for infantile hemangiomas: A mixed methods study.

The burden of treatment (BOT) related to propranolol treatment for infantile hemangiomas (IH) has never previously been explored. A modified validated questionnaire, the Treatment Burden Questionnaire, and one-on-one semi-structured interviews were used to assess the BOT for propranolol for IH. Out of 80 caregivers, the overall burden score was very low at 1.2 out of 10; thematic analysis of interviews grouped themes into administration, monitoring, financial, and associated anomalies. The BOT of propranolol for IH is very low but could be reduced further by offering age-based risk stratification related to feeding frequency and risk of hypoglycemia, pragmatic advice around timing of doses before sleep, and reducing frequency of vital sign monitoring.

Massive spinal epidural infantile hemangioma, image findings, and treatment: a case report and review of literature.

Spinal involvement of infantile hemangiomas is rare with the predilection to involve the epidural space. A proper diagnosis might be challenging due to the atypical location and variable/inconsistent use of the International Society for the Study of Vascular Anomalies (ISSVA) classification by radiologists, pathologists, and clinicians. A proper diagnosis of epidural infantile hemangioma is key due to the different aggressiveness of the treatment options with inconstant literature regarding the best available treatment. Herein, we present a case of a massive epidural infantile hemangioma successfully treated with only beta-blocker. We discuss the clinical, MRI, CT, ultrasound, and histological features of this lesion as we review the literature with the objective of addressing some of the confusion surrounding the subject.

Liposomal propranolol for treatment of infantile hemangioma at compounding pharmacies.

Infantile hemangiomas (IH) are common benign soft tissue tumors, frequently affecting infants. While Propranolol Hydrochloride (Pro HCl) has emerged as a promising treatment for IH, its topical application remains challenging due to the need for stable and efficacious carriers. This study investigates the potential of preformulated liposomes as carriers for topical delivery of Pro HCl for the treatment of IH in compounding pharmacies. Liposomes loaded with Pro HCl were prepared using active pharmaceutical ingredient or commercially available propranolol tablets and various dilution media, including Water for Injection (WFI), Dextrose 5%, and NaCl 0.9%. The physicochemical properties of the liposomal formulations (Pro HCl content, encapsulation efficiency, loading capacity, and colloidal stability) were assessed over a 90-day storage at 4 °C. In vitro release kinetics and transdermal permeation of Pro HCl from liposomes were also evaluated. Liposome properties were influenced by the dilution medium. Pro HCl content remained stable in liposomes encapsulating API (Lipo-Pro), regardless of the dilution medium. Lipo-Pro showed sustained drug release over time, suggesting its potential for maintaining therapeutic levels. Pro HCl exhibited enhanced transdermal permeability from Lipo-Pro compared to aqueous solution, indicating its potential for topical IH treatment. Preformulated liposomes offer a stable and effective carrier for Pro HCl, potentially suitable for extemporaneous preparations in compounding pharmacies. Their enhanced transdermal permeability presents a promising alternative for topical IH treatment. This study provides valuable insights into the development of innovative and effective drug delivery strategies for managing IH, with future research focusing on in vivo applications and therapeutic potential.

Urgent Treatment of Complicated Ulcerated Infantile Hemangioma with ß-Blockers via Telemedicine: A Case Report.

Introduction: Infantile hemangiomas (IH) exacerbated by ulceration invariably necessitate hospitalization, although simple IHs are sometimes managed remotely. Furthermore, according to international regulations, ß-blocker medication for such hemangiomas should be systemic and performed in a clinic, especially if there is infection and risk of bleeding. Case: War in Ukraine made it impossible to hospitalize and properly examine a patient with a complex ulcerated and infected IH, forcing us to administer ß-blocker timolol therapy only through telemedicine. Conclusions: Our case demonstrates the possibility of successful distant treatment of IH with ulcer using only a topical ß-blocker carried out remotely through telemedicine, which is critical in the context of the COVID-19 pandemic, war, hostilities, or natural disasters where inpatient treatment is not available.

Aesthetic Reconstruction of the Sequelae of Large Facial Involuted Infantile Hemangioma with Tissue Expanders.

BACKGROUND: Large involuted infantile hemangioma remains a challenge in facial reconstruction. The characteristic fibrofatty residuum and multiple subunits/tissues involvement contribute significantly to the difficulty of surgical management. Tissue expander plays an important role in facial reconstruction, allowing plastic surgeons to repair skin damaged by both congenital and acquired defects. METHODS: Between 2009 and 2021, 30 patients who underwent tissue expansion surgery were reviewed in a single hospital. The demographic data, lesion characteristics, surgical approaches, complication rate, and aesthetic outcomes were analyzed. RESULTS: Thirty patients (5 men and 25 women) with a mean age of 14.03 ± 7.25 years (range, 4-33 years) were included. The mean follow-up is 35.92 months, ranging from 9 to 75 months. Tissue expansion-related complications include closed infection, 2/30 (6.67%); skin ischemia, 2/30 (6.67%); hematoma, 1/30 (3.33%); flap necrosis, 1/30 (3.33%). CONCLUSION: Large facial involuted infantile hemangiomas have variable patterns of presentation and necessitate tailored therapy. Tissue expansion is a reproducible approach to achieving aesthetic reconstruction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .