Denise W Metry

Medical College of Wisconsin, Milwaukee, Wisconsin, United States

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Publications (90)227.91 Total impact

  • Pediatric Dermatology 01/2014; 31(1):103-4. · 1.04 Impact Factor
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    ABSTRACT: 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.
    The American journal of cardiology 09/2013; · 3.58 Impact Factor
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    ABSTRACT: Segmental hemangiomas of the head and neck can be associated with multiple congenital anomalies in the disorder known as PHACE syndrome (OMIM 606519) (posterior fossa malformations, hemangioma, arterial anomalies, cardiac defects, and eye anomalies). All reported cases of PHACE syndrome to date have been sporadic, and the genetic basis of this disorder has not yet been established. PHACE syndrome has a striking female predominance which has raised the question of X-linked inheritance. In this study, the X chromosome-inactivation (XCI) patterns of 31 females with PHACE syndrome and their mothers were analyzed using blood-derived DNA and X-chromosome locus methylation assay. This study was performed to test the hypothesis that some cases of PHACE syndrome are due to X-linked inheritance and favorable skewing in the mothers may protect against a severe phenotype, but the clinical phenotype may be unmasked in daughters with a random pattern of X-inactivation. XCI analysis was informative in 27/31 mothers. Our results identified skewed XCI in 5 of 27 (19%) informative mothers, which is not statistically significant with a p value of 0.41. None of the mothers reported significant medical problems, although a full PHACE work-up has not been performed in these individuals. Skewed XCI in the mothers of children with PHACE was identified in only a minority of cases. Based on these results, genetic heterogeneity is likely in PHACE syndrome, although it is possible a subset of cases are caused by a mutation in an X-linked gene.
    Molecular syndromology 03/2013; 4(3):114-8.
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    ABSTRACT: Infantile hemangiomas (IHs) are common neoplasms composed of proliferating endothelial-like cells. Despite the relative frequency of IH and the potential severity of complications, there are currently no uniform guidelines for treatment. Although propranolol has rapidly been adopted, there is significant uncertainty and divergence of opinion regarding safety monitoring, dose escalation, and its use in PHACE syndrome (PHACE = posterior fossa, hemangioma, arterial lesions, cardiac abnormalities, eye abnormalities; a cutaneous neurovascular syndrome characterized by large, segmental hemangiomas of the head and neck along with congenital anomalies of the brain, heart, eyes and/or chest wall). A consensus conference was held on December 9, 2011. The multidisciplinary team reviewed existing data on the pharmacologic properties of propranolol and all published reports pertaining to the use of propranolol in pediatric patients. Workgroups were assigned specific topics to propose protocols on the following subjects: contraindications, special populations, pretreatment evaluation, dose escalation, and monitoring. Consensus protocols were recorded during the meeting and refined after the meeting. When appropriate, protocol clarifications and revision were made and agreed upon by the group via teleconference. Because of the absence of high-quality clinical research data, evidence-based recommendations are not possible at present. However, the team agreed on a number of recommendations that arose from a review of existing evidence, including when to treat complicated IH; contraindications and pretreatment evaluation protocols; propranolol use in PHACE syndrome; formulation, target dose, and frequency of propranolol; initiation of propranolol in infants; cardiovascular monitoring; ongoing monitoring; and prevention of hypoglycemia. Where there was considerable controversy, the more conservative approach was selected. We acknowledge that the recommendations are conservative in nature and anticipate that they will be revised as more data are made available.
    PEDIATRICS 12/2012; · 4.47 Impact Factor
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    ABSTRACT: PHACE syndrome is the association of large segmental facial hemangiomas and congenital anomalies, such as posterior fossa malformations, cerebral arterial anomalies, coarctation of the aorta, eye anomalies, and sternal defects. To date, the reported cases of PHACE syndrome have been sporadic, suggesting that PHACE may have a complex pathogenesis. We report here genomic copy number variation (CNV) analysis of 98 individuals with PHACE syndrome as a first step in deciphering a potential genetic basis of PHACE syndrome. A total of 3,772 CNVs (2,507 duplications and 1,265 deletions) were detected in 98 individuals with PHACE syndrome. CNVs were then eliminated if they failed to meet established criteria for quality, spanned centromeres, or did not contain genes. CNVs were defined as "rare" if not documented in the database of genomic variants. Ten rare CNVs were discovered (size range: 134-406 kb), located at 1q32.1, 1q43, 3q26.32-3q26.33, 3p11.1, 7q33, 10q24.32, 12q24.13, 17q11.2, 18p11.31, and Xq28. There were no rare CNV events that occurred in more than one subject. Therefore, further study is needed to determine the significance of these CNVs in the pathogenesis of PHACE syndrome.Journal of Investigative Dermatology advance online publication, 25 October 2012; doi:10.1038/jid.2012.367.
    Journal of Investigative Dermatology 10/2012; · 6.19 Impact Factor
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    ABSTRACT: The objective of this retrospective study of patients evaluated between July 2008 and October 2011 in seven pediatric dermatology centers was to combine collective clinical experience using oral propranolol therapy in 32 infants with PHACE syndrome (Posterior fossa [brain malformations present at birth], Hemangioma [usually covering a large area of the skin of the head or neck >5 cm]; Arterial lesions [abnormalities of the blood vessels in the neck or head]; Cardiac abnormalities or aortic coarctation [abnormalities of the heart or blood vessels that are attached to the heart]; Eye abnormalities) with cervical or intracranial arterial anomalies. Patients were given an average daily dose of oral propranolol of 1.8 mg/kg divided two or three times per day for an average duration of 12.3 months. The main outcome measure was adverse neurologic events. Seven (22%) patients were categorized as being at higher risk for stroke, defined on magnetic resonance imaging as severe, long-segment narrowing or nonvisualization of major cerebral or cervical vessels without anatomic evidence of collateral circulation, often in the presence of concomitant cardiovascular comorbidities. Only one patient developed a change in neurologic status during propranolol treatment: mild right hemiparesis that remained static and improved while propranolol was continued. An additional three patients had worsening hemangioma ulceration or tissue necrosis during therapy. This is the largest report thus far of patients with PHACE syndrome treated with propranolol. Although no catastrophic neurologic events occurred, serious complications, particularly severe ulcerations, were seen in a minority of patients, and given the sample size, we cannot exclude the possibility that propranolol could augment the risk of stroke in this population. We propose radiologic criteria that may prove useful in defining PHACE patients as being at high or standard risk for stroke. We continue to advise caution in using systemic beta-blockers, particularly for children with vascular anomalies at higher risk for stroke. Use of the lowest possible dosage, slow dosage titration, three times per day dosing to minimize abrupt changes in blood pressure, and close follow-up, including neurologic consultation as needed, are recommended.
    Pediatric Dermatology 09/2012; · 1.04 Impact Factor
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    ABSTRACT: 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.
    Journal of child neurology 07/2012; · 1.59 Impact Factor
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    ABSTRACT: PHACE syndrome (OMIM #606519) is a neurocutaneous syndrome of unknown etiology and pathogenesis. We report on an individual with PHACE syndrome with a complete deletion of SLC35B4 on 7q33. In order to further analyze this region, SLC35B4 was sequenced for 33 individuals with PHACE syndrome and one parental set. Common polymorphisms with a possible haplotype but no disease causing mutation were identified. Sixteen of 33 samples of the PHACE syndrome patients were also analyzed for copy number variations using high-resolution oligo-comparative genomic hybridization (CGH) microarray. A second individual in this cohort had a 26.5 kb deletion approximately 80 kb upstream of SLC35B4 with partial deletion of the AKR1B1 on 7q33. The deletions observed on 7q33 are not likely the singular cause of PHACE syndrome; however, it is possible that this region provides a genetic susceptibility to phenotypic expression with other confounding genetic or environmental factors.
    American Journal of Medical Genetics Part A 04/2012; 158A(6):1363-7. · 2.30 Impact Factor
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    ABSTRACT: PHACE is an acronym for posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities. Several case reports of arterial ischemic stroke (AIS) in individuals with PHACE have been published, but risk factors for AIS in PHACE have not been clearly defined. The objective of this article is to review all cases of stroke in PHACE in children and describe clinical characteristics that may be associated with an increased risk of AIS. A literature and registry search was conducted to identify patients with PHACE who had experienced AIS. Data were analyzed to determine age of onset, presenting signs and symptoms, and clinical features among this cohort compared with PHACE without AIS. Twenty-two individuals with PHACE and AIS were identified. Imaging of the arteries of the head and neck was reported in 20 of 22. Narrowing or nonvisualization of at least 1 great cerebral vessel was present in 19 of 20 and of those, 15 had ≥ 2 vessels involved. Aortic arch anomalies were reported in 13 of 22 individuals. Aplasia, hypoplasia, or occlusion of a major cerebral artery appears to be a significant risk factor for AIS in children with PHACE, especially when >1 vessel is involved or if there is coarctation of the aorta.
    Stroke 03/2012; 43(6):1672-4. · 6.16 Impact Factor
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    ABSTRACT: 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. Pediatr Blood Cancer 2012; 59: 934-938. © 2012 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 02/2012; 59(5):934-8. · 2.35 Impact Factor
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    ABSTRACT: 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]). Instrument development and reliability study. Academic research. 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. Interrater and intrarater reliability. 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. 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.
    Archives of dermatology 02/2012; 148(2):197-202. · 4.76 Impact Factor
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    ABSTRACT: To highlight an association of facial segmental hemangiomas with gastrointestinal bleeding in infants with infantile hemangiomas. We conducted a multicenter retrospective case series study. Ten female patients met study inclusion criteria; 8 were Caucasian, 9 had a facial segmental hemangioma, and 9 cases met the diagnostic criteria for definitive posterior fossa malformations, hemangioma, arterial lesions, cardiac anomalies/coarctation of the aorta and eye abnormalities syndrome with abnormalities of the aorta and cerebral arteriopathy. Severe gastrointestinal bleeding requiring blood transfusion occurred in 9 cases, with age at presentation of gastrointestinal bleeding ranging from 8 days to 6 months. When detected, the location of the hemangioma in the small intestine was in the distribution of the superior mesenteric artery. More than one agent was required to control the gastrointestinal bleeding, including oral or intravenous steroids, vincristine, oral propranolol, interferon, and resection of the small intestine. All cases needed ongoing support care with red blood cell transfusions. Gastrointestinal bleeding is a rare complication of true infantile hemangioma. The segmental pattern of the cutaneous hemangioma associated with gastrointestinal bleeding should suggest a segmental infantile hemangioma of the lower gastrointestinal tract.
    The Journal of pediatrics 01/2012; 160(6):1021-6.e3. · 4.02 Impact Factor
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    ABSTRACT: 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. 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. The radiological images of 20 cases of lumbosacral infantile hemangioma associated with spinal dysraphism were reviewed. 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. A range of spinal anomalies is associated with cutaneous lumbosacral infantile hemangiomas and MRI can be used to characterize these abnormalities.
    Pediatric Radiology 12/2011; 42(3):315-20. · 1.57 Impact Factor
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    ABSTRACT: 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.
    Pediatric Dermatology 09/2011; 29(5):610-3. · 1.04 Impact Factor
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    ABSTRACT: To describe the clinical presentation and risk of PHACE syndrome in infants with large facial hemangiomas and concomitant airway hemangiomas. 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. Six academic pediatric dermatology clinics. The study included 17 patients younger than 1 year who were diagnosed as having large (>22 cm(2)) facial hemangiomas and airway hemangiomas. 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. 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.
    Archives of otolaryngology--head & neck surgery 07/2011; 137(7):680-7. · 1.92 Impact Factor
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    ABSTRACT: Multiple cutaneous infantile hemangiomas have been associated with hepatic hemangiomas. Screening of infants with five or more cutaneous infantile hemangiomas with abdominal ultrasound is often recommended. The aim of this study was to determine the frequency with which hepatic hemangiomas occur in infants with five or more cutaneous infantile hemangiomas compared to those with one to four cutaneous infantile hemangiomas and to characterize the clinical features of these hepatic hemangiomas. A multicenter prospective study of children with cutaneous infantile hemangiomas was conducted at pediatric dermatology clinics at Hemangioma Investigator Groups sites in the United States, Canada, and Spain between October 2005 and December 2008. Data were collected, and abdominal ultrasonography was performed on infants younger than 6 months old with five or more cutaneous infantile hemangiomas and those with one to four cutaneous infantile hemangiomas. Twenty-four (16%) of the 151 infants with five or more cutaneous infantile hemangiomas had hepatic hemangiomas identified on abdominal ultrasound, versus none of the infants with fewer than five (p = 0.003). Two of the 24 infants with hepatic hemangiomas received treatment specifically for their hepatic hemangiomas. Infants with five or more cutaneous infantile hemangiomas have a statistically significantly greater frequency of hepatic hemangiomas than those with fewer than 5. These findings support the recommendation of five or more cutaneous infantile hemangiomas as a threshold for screening infants younger than 6 months old for hepatic hemangiomas but also demonstrate that the large majority of these infants with hepatic hemangiomas do not require treatment.
    Pediatric Dermatology 05/2011; 28(3):245-53. · 1.04 Impact Factor
  • Archives of dermatology 03/2011; 147(3):345-50. · 4.76 Impact Factor
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    ABSTRACT: We present two cases of PHACE syndrome (an acronym for the neurocutaneous association of posterior fossa defects, hemangiomas, arterial anomalies, cardiac anomalies, and eye defects) associated with arteriovenous fistulae/malformation (AVF/AVM). While cerebral arterial anomalies are a main feature of this syndrome, the diagnostic criteria do not include AVF/AVM. To our knowledge, our cases are the fifth and sixth reported cases of PHACE syndrome and AVF/AVM occurring in the same patient. Given the rarity of both PHACE syndrome and AVM, and the known relationship between cerebrovascular anomalies and segmental infantile hemangioma, we suggest that the simultaneous occurrence in these patients is related.
    Pediatric Dermatology 01/2011; 28(2):180-4. · 1.04 Impact Factor
  • Sarah J Seyfer, Nnenna G Agim, Denise W Metry
    Pediatric Dermatology 01/2011; 28(2):189-90. · 1.04 Impact Factor
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    ABSTRACT: We report an extremely rare case of a patient with a large, cervical, and upper thoracic cutaneous hemangioma associated with a separate, underlying mediastinal hemangioma extending to the epidural space causing significant spinal cord compression. A 6-week-old female presented with decreased movement of her right arm and bilateral lower extremity hyperreflexia. Her arm weakness progressed to paralysis over the course of 24 h. She underwent emergent surgical decompression and medical therapy with propranolol and systemic corticosteroids. While several recent reports have described dramatic responses of hemangiomas to propranolol, this is the first case in which it was used as part of a multimodal approach to symptomatic spinal cord compression. The infant improved immediately after surgery. She is neurologically intact and has radiographic regression of the hemangiomas on follow-up examination 6 months later.
    Child s Nervous System 12/2010; 26(12):1799-805. · 1.24 Impact Factor

Publication Stats

1k Citations
227.91 Total Impact Points

Institutions

  • 2010–2013
    • Medical College of Wisconsin
      • • Department of Dermatology
      • • Division of Pediatric Urology
      Milwaukee, Wisconsin, United States
  • 2008–2013
    • Texas Children's Hospital
      Houston, Texas, United States
  • 2000–2013
    • Baylor College of Medicine
      • Department of Dermatology
      Houston, Texas, United States
  • 2010–2011
    • Indiana University-Purdue University Indianapolis
      • • Department of Dermatology
      • • Department of Biostatistics
      Indianapolis, IN, United States
  • 2009
    • Harvard Medical School
      • Department of Dermatology
      Boston, MA, United States
  • 2006–2008
    • University of California, San Francisco
      • Department of Dermatology
      San Francisco, CA, United States
  • 2007
    • University of North Carolina at Chapel Hill
      • Department of Dermatology
      Chapel Hill, NC, United States
  • 2004
    • Changi General Hospital
      • Department of Dermatology
      Singapore, Singapore