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.

LUMBAR syndrome-OEIS complex overlap: A case series and review.

We present three new and six published infants with overlapping features of LUMBAR syndrome (lower body hemangioma, urogenital anomalies, spinal cord malformations, bony deformities, anorectal/arterial anomalies and renal anomalies) and OEIS complex (omphalocele, exstrophy, imperforate anus, and spinal defects), also known as cloacal exstrophy. OEIS is included under the recently proposed umbrella coined recurrent constellations of embryonic malformations (RCEMs). The RCEMs represent a phenotypically overlapping spectrum of rare disorders of caudal dysgenesis with unknown cause but likely shared pathogenesis. It has recently been proposed that LUMBAR be considered an RCEM. This report of infants with combined features of OEIS and LUMBAR is the first to demonstrate an overlap between LUMBAR and another RCEM, which supports LUMBAR's inclusion within the RCEM spectrum.

An infant with LUMBAR syndrome complicated by severe perineal ulceration managed with diverting colostomy.

Infantile hemangiomas are the most common childhood vascular lesions. LUMBAR syndrome (lower body hemangioma, urogenital abnormalities/ulceration, myelopathy, bony deformities, anorectal malformations/arterial anomalies, and rectal anomalies) warrants special treatment considerations. Here we describe a case of an infant with LUMBAR syndrome who presented with severe perineal ulceration refractory to standard medical therapy and was managed with a temporary diverting sigmoid colostomy. This case demonstrates that adjunctive surgical management can be considered in infants with aggressive perineal wounds refractory to standard medical therapy.

Green nail syndrome complicated by pseudomonal keratitis in a teenager with artificial nails.

Green nail syndrome (GNS) is a pseudomonal nail infection that presents with characteristic green nail discoloration. It typically affects patients with preexisting nail conditions or chronic exposure to wet environments but can also be seen with local trauma. Our patient presented with a pseudomonal corneal ulcer of the left eye and was incidentally found to have GNS, which developed after home artificial nail application. This unusual case of extensive pediatric GNS illustrates a rare and serious infectious complication of prolonged artificial nails.

Successful use of telemedicine for evaluation of infantile hemangiomas during the early COVID-19 pandemic: A cross-sectional study.

BACKGROUND/OBJECTIVES: The COVID-19 pandemic prompted a rapid expansion in the use of telemedicine. This study aimed to assess the experiences of hemangioma specialists utilizing telemedicine during the COVID-19 pandemic to evaluate and manage infantile hemangiomas (IH), including perceived effectiveness of different modalities and barriers to care delivery. METHODS: Multicenter cross-sectional study asking providers to describe their experiences using telemedicine for initial evaluation of IH from March to September 2020. RESULTS: The study included 281 patients from 15 medical centers internationally. Median time from referral to evaluation was 17 days. Median physician confidence in performing evaluations via telemedicine was 95.0 (IQR 90.0-100.0). Most evaluations were performed via video communication with photographs or audio communication with photographs; when not initially available, photographs were requested in 51.4%. Providers preferred follow-up modalities that included photographs. CONCLUSIONS: Physicians with extensive expertise in managing IH are confident in their abilities to assess and manage IH via telemedicine including initiating treatment in patients without risk factors for beta-blocker therapy. There was a preference for hybrid modalities that included photographs. The data suggest that telemedicine can be effective for managing IH and may decrease wait times and improve specialist reach to underserved areas.

The genetics of vascular birthmarks.

One in 10 infants are born with a vascular birthmark each year. Some vascular birthmarks, such as infantile hemangiomas, are common, while vascular malformations, such as capillary, lymphatic, venous, and arteriovenous malformations, are less so. Diagnosing uncommon vascular birthmarks can be challenging, given the phenotypic heterogeneity and overlap among these lesions. Both sporadic and germline variants have been detected in various genes associated with vascular birthmarks. Identification of these genetic variants offers insight into both diagnosis and underlying molecular pathways and can be fundamental in the discovery of novel therapeutic approaches. The PIK3/AKT/mTOR and RAS/MEK/ERK signaling pathways, which mediate cell growth and angiogenesis, are activated secondary to genetic variations in vascular malformations. Somatic variants in TEK (TIE2) and PIK3CA cause venous malformations. Variants in PIK3CA also cause lymphatic malformations as well as a number of overgrowth syndromes associated with vascular anomalies. Variants in GNAQ and GNA11 have been identified in both so-called "congenital" hemangiomas and capillary malformations. RASA1 and EPHB4 variants are associated with capillary malformation-arteriovenous malformation syndrome. This review discusses the genetics of vascular birthmarks, including the various phenotypes, genetic variants, pathogenesis, associated syndromes, and new diagnostic techniques.

Management of infantile hemangiomas during the COVID pandemic.

The COVID-19 pandemic has caused significant shifts in patient care including a steep decline in ambulatory visits and a marked increase in the use of telemedicine. Infantile hemangiomas (IH) can require urgent evaluation and risk stratification to determine which infants need treatment and which can be managed with continued observation. For those requiring treatment, prompt initiation decreases morbidity and improves long-term outcomes. The Hemangioma Investigator Group has created consensus recommendations for management of IH via telemedicine. FDA/EMA-approved monitoring guidelines, clinical practice guidelines, and relevant, up-to-date publications regarding initiation and monitoring of beta-blocker therapy were used to inform the recommendations. Clinical decision-making guidelines about when telehealth is an appropriate alternative to in-office visits, including medication initiation, dosage changes, and ongoing evaluation, are included. The importance of communication with caregivers in the context of telemedicine is discussed, and online resources for both hemangioma education and propranolol therapy are provided.

Hamartomas and midline anomalies in association with infantile hemangiomas, PHACE, and LUMBAR syndromes.

BACKGROUND/OBJECTIVE: The pathogenesis of infantile hemangiomas (IH), PHACE, and LUMBAR syndromes remains unknown. We aim to describe histopathologic features of midline anomalies associated with IH, including patients with PHACE and LUMBAR syndromes. METHODS: A multicenter retrospective chart review was performed to identify patients with IH, PHACE, and LUMBAR syndrome with histopathologic specimens from sternal or midline anomalies. A total of 18 midline lesions from 13 patients were included. Out of 18, 14 midline lesions underwent both histopathologic and clinical review. Three hamartoma-like chin plaques and one supraumbilical raphe underwent only clinical review. RESULTS: All 13 patients had midline lesions and IH. Histopathologic diagnoses were as follows: rhabdomyomatous mesenchymal hamartoma (3), folliculosebaceous cystic hamartoma (1), fibroepithelial polyp (1), verrucous epidermal hyperplasia with vascular proliferation and fibroplasia (1), congenital midline cervical cleft (1), pericardium with fibrosis (1), fibrous components with increased collagen (1), atrophic skin/membrane (3), angiolipomatous mass with neural components (1), and lipomatous mass (1). Due to the retrospective nature of this study, it was not possible to obtain pathology slides for all midline lesions that had previously been biopsied or resected. We show clinically and histopathologically a new association between PHACE syndrome and rhabdomyomatous mesenchymal hamartoma (RMH), in addition to demonstrating the association between PHACE syndrome and chin hamartomas. We also display histopathologic findings seen in midline lesions resected from LUMBAR patients. CONCLUSION: Rhabdomyomatous mesenchymal hamartoma is thought to be related to aberrations of mesenchymal cells during development; therefore, this may provide clues to the pathogenesis of IH and related syndromes.

Structural malformations of the brain, eye, and pituitary gland in PHACE syndrome.

PHACE syndrome is the association of segmental facial hemangiomas with congenital arterial, brain, cardiac, and ocular anomalies. Structural brain malformations affect 41-52% of PHACE patients and can be associated with focal neurologic deficits, developmental delays, and/or intellectual disability. To better characterize the spectrum of structural brain and other intracranial anomalies in PHACE syndrome, MRI scans of the head/neck were retrospectively reviewed in 55 patients from the PHACE Syndrome International Clinical Registry and Genetic Repository. All registry patients with a diagnosis of definite PHACE syndrome who had MRI scans of satisfactory quality were included. Of 55 patients, 34 (62%) demonstrated ≥1 non-vascular intracranial anomaly; structural brain malformations were present in 19 (35%). There was no difference in the prevalence of brain anomalies between genders. Brain anomalies were more likely in patients with S1 and/or S2 distribution of facial hemangioma. The most common structural brain defects were cerebellar hypoplasia (25%) and fourth ventricle abnormalities (13%). Dandy-Walker complex and malformations of cortical development were present in 9% and 7%, respectively. Extra-axial findings such as pituitary anomalies (18%) and intracranial hemangiomas (18%) were also observed. Six patients (11%) had anomalies of the globes or optic nerve/chiasm detectable on MRI. Brain malformations comprise a diverse group of structural developmental anomalies that are common in patients with PHACE syndrome. Along with brain malformations, numerous abnormalities of the pituitary, meninges, and globes were observed, highlighting the need for careful radiologic assessment of these structures in the neuroimaging workup for PHACE syndrome.

Congenital cardiac, aortic arch, and vascular bed anomalies in PHACE syndrome (from the International PHACE Syndrome Registry).

PHACE syndrome represents the association of large infantile hemangiomas of the head and neck with brain, cerebrovascular, cardiac, ocular, and ventral or midline defects. Cardiac and cerebrovascular anomalies are the most common extracutaneous features of PHACE, and they also constitute the greatest source of potential morbidity. Congenital heart disease in PHACE is incompletely described, and this study was conducted to better characterize its features. This study of the International PHACE Syndrome Registry represents the largest central review of clinical, radiologic, and histopathologic data for cardiovascular anomalies in patients with PHACE to date. Sixty-two (41%) of 150 subjects had intracardiac, aortic arch, or brachiocephalic vessel anomalies. Aberrant origin of a subclavian artery was the most common cardiovascular anomaly (present in 31 (21%) of 150 subjects). Coarctation was the second most common anomaly, identified in 28 (19%) of 150 subjects, and can be missed clinically in patients with PHACE because of the frequent association of arch obstruction with aberrant subclavian origin. Twenty-three (37%) of 62 subjects with cardiovascular anomalies required procedural intervention. A greater percentage of hemangiomas were located on the left side of the head and neck in patients with coarctation (46% vs 39%); however, hemangioma distribution did not predict the presence of cardiovascular anomalies overall. In conclusion, PHACE is associated with a high risk of congenital heart disease. Cardiac and aortic arch imaging with detailed assessment of arch patency and brachiocephalic origins is essential for any patient suspected of having PHACE. Longitudinal investigation is needed to determine the long-term outcomes of cardiovascular anomalies in PHACE.

Neurodevelopmental abnormalities in children with PHACE syndrome.

Prior case reports have identified neurodevelopmental abnormalities in children with PHACE syndrome, a neurocutaneous disorder first characterized in 1996. In this multicenter, retrospective study of a previously identified cohort of 93 children diagnosed with PHACE syndrome from 1999 to 2010, 29 children had neurologic evaluations at ≥ 1 year of age (median age: 4 years, 2 months). In all, 44% had language delay, 36% gross motor delay, and 8% fine motor delay; 52% had an abnormal neurological exam, with speech abnormalities as the most common finding. Overall, 20 of 29 (69%) had neurodevelopmental abnormalities. Cerebral, but not posterior fossa, structural abnormalities were identified more often in children with abnormal versus normal neurodevelopmental outcomes (35% vs. 0%, P = .04). Neurodevelopmental abnormalities in young children with PHACE syndrome referred to neurologists include language and gross motor delay, while fine motor delay is less frequent. Prospective studies are needed to understand long-term neurodevelopmental outcomes.

Variable response to propranolol treatment of kaposiform hemangioendothelioma, tufted angioma, and Kasabach-Merritt phenomenon.

Propranolol is a non-selective beta-adrenergic antagonist successfully used in a case of kaposiform hemangioendothelioma (KHE) associated with Kasabach-Merritt phenomenon (KMP). We report 11 patients treated with propranolol for KHE and the related variant tufted angioma (TA), six of whom also had KMP. The varied responses to treatment, with only 36% responding in our series, demonstrate the need for further study of this medication before routine use for these indications.

Measuring the severity of infantile hemangiomas: instrument development and reliability.

OBJECTIVES: To develop instruments that measure the severity of infantile hemangiomas (Hemangioma Severity Scale [HSS]) and the complications of infantile hemangiomas for longitudinal use (Hemangioma Dynamic Complication Scale [HDCS]). DESIGN: Instrument development and reliability study. SETTING: Academic research. PARTICIPANTS: The HSS and the HDCS were developed through the collaborative effort of members of the Hemangioma Investigator Group Research Core, an expert multi-institutional research group. After development of the scales, 13 pediatric dermatologists used the HSS to score 20 different hemangiomas. In addition, 12 pediatric dermatologists used the HDCS to score hemangioma-related complications for 24 clinical scenarios. Interrater and intrarater reliability was measured for both scales. MAIN OUTCOME MEASURES: Interrater and intrarater reliability. RESULTS: For the HSS, interrater reliability and intrarater reliability exceeded 99%. Similarly, the HDCS had a high rate of interrater agreement; for individual items, agreement among raters was 67% to 100%, with most clinical scenarios demonstrating greater than 90% agreement. Intrarater reliability was excellent for all individual items of the HDCS. CONCLUSION: The HSS and the HDCS are reliable scales that can be used to measure the severity of infantile hemangiomas, including the severity of complications for longitudinal use.

Neonatal linear immunoglobulin a bullous dermatosis: a rare presentation.

Linear immunoglobulin A bullous dermatosis (LABD) is an autoimmune blistering disease that most commonly presents in preschool-aged children. There have been few neonatal reports, all of which had life-threatening aerodigestive complications requiring mechanical intervention and systemic therapy. We present a case of LABD in a neonate who had an uncomplicated course and was treated conservatively with only low-potency topical corticosteroids and wound care before resolution of his skin lesions.

Spinal dysraphism associated with the cutaneous lumbosacral infantile hemangioma: a neuroradiological review.

BACKGROUND: Spinal dysraphism is suspected in patients with midline abnormalities, especially in those with lumbosacral cutaneous markings. A recent prospective study demonstrated that isolated cutaneous infantile hemangiomas (IH) of the lumbosacral region have one of the highest risks (relative risk of 438) of associated spinal dysraphism. OBJECTIVE: The specific types of dysraphism and radiological findings associated with cutaneous IH of the lumbosacral region have not been described in detail, to the best of our knowledge. The aim of this multicenter study is to retrospectively classify types of spinal anomalies associated with the cutaneous lumbosacral IH. MATERIALS AND METHODS: The radiological images of 20 cases of lumbosacral infantile hemangioma associated with spinal dysraphism were reviewed. RESULTS: Tethered cord was found in 60% of the 20 cases, spinal lipoma was present in 50% and 45% had intraspinal hemangiomas. Sinus tract was found in 40% of the children. CONCLUSION: A range of spinal anomalies is associated with cutaneous lumbosacral infantile hemangiomas and MRI can be used to characterize these abnormalities.

Clinical spectrum and risk of PHACE syndrome in cutaneous and airway hemangiomas.

OBJECTIVE: To describe the clinical presentation and risk of PHACE syndrome in infants with large facial hemangiomas and concomitant airway hemangiomas. DESIGN: The study involved a case series of infants with cutaneous hemangiomas and airway hemangiomas extracted from a prospective multicenter cohort study. Data regarding clinical features, diagnosis, treatment, and clinical course were obtained from medical charts and physician intake forms. All patients were evaluated for PHACE syndrome using a standardized protocol. SETTING: Six academic pediatric dermatology clinics. PATIENTS: The study included 17 patients younger than 1 year who were diagnosed as having large (>22 cm(2)) facial hemangiomas and airway hemangiomas. RESULTS: Thirteen patients (76%) had hemangiomas in the bilateral mandibular distribution. Other observed facial patterns included limited involvement of the lip and chin, unilateral reticular frontotemporal and preauricular hemangiomas, and large unilateral hemifacial hemangiomas. Fourteen patients (82%) had symptomatic airway involvement. All symptomatic patients had subglottic airway hemangiomas. The airway hemangioma was circumferential in 10 patients (58%) and more focal in distribution in 7 patients (42%). All patients were treated with oral prednisolone. Eleven patients required additional multimodal therapy. Eight patients (47%) met the criteria for PHACE syndrome. CONCLUSIONS: Airway hemangiomas represent a potentially fatal complication of infantile hemangiomas. Our data highlight cutaneous presentations in patients with subglottic hemangiomas and large (>22 cm(2)) cutaneous hemangiomas. PHACE syndrome was detected in 8 such patients (47%) in our series.