Adolescents and Adults Presenting at VACS with symptoms suggesting prior IH and PHACE
Infantile hemangiomas are the most common benign vascular tumor of infants and children. The reported incidence is as frequent as 12%. A subgroup of patients with infantile hemangiomas most commonly facial hemangioma exhibit associated structurally anomalies of the brain, arteries, cardiovascular system eye, sternal clefting and supraumbilical raphe have a disorder known as PHACE. Infants born today with a large facial hemangioma and 1-2 of the other associated diagnostic criteria, Metry et.al. are considered for the PHACE dignosis. These patients are followed and monitored for long term complications of PHACE. However, many adolescents and adults may not know they had had a prior facial hemangioma and unless symptomatic may not know they have any structural anomalies for which they should be concerned.
In the 20 years I have been working with vascular anomaly families I have seen many children with large facial hemangioma. Many of these children had laser or medical treatment to resolve the hemangioma in early childhood. PHACE was first named in 1996 by Dr. Ilonia Frieden, the Diagnostic Criteria was not published by Metry and associates until 2009. Until this time there was no consensus on the diagnosis of the association of these symptoms and many patients simply did not receive a diagnosis beyond, “large hemangioma”. Where are these individuals today and what is happening with them is of particular interest to us at NOVA. We are interested in knowing what has happened to those we have lost contact with on a personal level but also from a medical and scientific level. There is so much that can be learned from the medical history of these individuals that can help direct treatment and research.
At the 2014 ISSVA meeting Dr. Fran Blei and associates presented a poster abstract on the Adult Faces of PHACE. Three cases of PHACE syndrome incidentally diagnosed radiologically after presentation with acute neurological symtoms were presented. Two patients suffered post traumatic concussion and seizure and one patient chronic hearing loss. The radiologic exam of the carotid arteries, subclavian arteries and brain demonstrated similarities to findings with PHACE. The medical history revealed the patients had a facial segmental hemangioma of infancy. The published diagnostic criteria for PHACE allows the clinician to make the diagnosis of PHACE in the adult patient even after the hemangioma has involuted or has been resolved by treatment.
Garzon and associates also presented a poster abstract at the 2014 ISSVA meeting. This review of the literature searched for definite and possible PHACE based on the diagnostic criteria of PHACE. Twenty-seven definite and thirty-four possible cases were identified in adult and adolescent case studies. Infantile Hemangioma was identified in 100% of the cases reported and 92% of he cases had arterial abnormalities. Other associated symptoms were reported as CNS abnormalities 57%, cardiac abnormalities 35%, eye abnormalities 15%. In 23 of the case a neurological status was described. 57% had developmental delay or impaired IQ, 22% had TIA or stroke, 9% had seizures and 9% had headaches, 26% were described as neuro-developmentally normal or functioning independently. This abstract summary tells us that we need a better recognition for adult patients with PHACE. Understanding the true prevalence will help us better understand our outcomes in this patient population.
The incidence of infantile hemangioma is up to 12%, the true incidence of the associated diagnosis of PHACE syndrome is unknown. Today a diagnostic criteria helps the clinician diagnose PHACE syndrome in early infancy and monitor, manage and treat any of the associated abnormalities early leading to better outcomes. Unfortunately there is an unknown number of individuals who may have structural abnormalities of PHACE and not have them identified. These patients are at risk for cardiovascular, and CNS incident. Identifying these individuals in the population through screening will help us understand the long term clinical outcomes for PHACE and direct treatment for the infants today. If you had a child with a large facial hemangioma, any of the symptoms associated with PHACE and were not previously diagnosed with PHACE you may want to consider speaking with someone about the PHACE diagnosis.
ISSVA Announces 2014 Award Winners
Elisa Boscolo, Kyu-Tae Kang, Nisha Limaye, Julie Soblet, Melanie Uebelhoer, Mariut Natynki, Carlo Brugnara, Emmanuel Seront, Lauri Eklund, Miikka Vikkula, Laurence Boon
Michel Wassef, Denise Adams, Ahmad Alomari, Eulalia Baselga, Alejandro Berenstein, Francine Blei, Patricia Burrows, Ilona Frieden, Maria Garzon, Juan-Carlos Lopez-Gutierrez, David Lord, Julie Prendiville and Miikka Vikkula
Pedro Redondo, Leyre Aguado, Maider Pretel, Laura Marques, Alejandro Sierra, Pablo Boixeda and Eulalia Baselga
sildenafil for the treatment of lymphatic malformations.
Lymphatic Malformations can be very challenging for the clinician to treat. Interventions include sclerotherapy and surgery are invasive and may result in complications and recurrence of the lesion. A new study published in the Journal of the American Academy of Dermatology 2014 March 20 pii: S0190-9622(14)0119-0 examines sildenafil generic for viagra to treat lymphatic malformations.
Patients were placed on 20 weeks of oral sildenafil, LM were assessed for volum and symptoms. Sever male children and 3 females were observed; ages 13-85 months. There was a therapeutic response of softening and compressiblity in all patients. Adverse events were minimal. A larger randomized controlled study is needed to better verify these results however; it seems sildenafil may reduce lymphatic malformation volume and symptoms in some patients.
J Am Acad Dermatol. 2014 Mar 20. pii: S0190-9622(14)01119-0. doi: 10.1016/j.jaad.2014.02.005. [Epub ahead of print]
An open-label study to evaluate sildenafil for the treatment of lymphatic malformations.
- 1Department of Dermatology, Lucile Packard Children’s Hospital at the Stanford University School of Medicine, Palo Alto.
- 2Department of Radiology, Stanford University School of Medicine, Stanford.
- 3Department of Dermatology, Lucile Packard Children’s Hospital at the Stanford University School of Medicine, Palo Alto. Electronic address: firstname.lastname@example.org.
Summary on Propranolol
Just finished reading 6 Abstracts on the use of Propranolol in the management of Infantile Hemangioma. All of the information came from presentations at the 2014 ISSVA meeting in Melbourne, Australia last week. A summary is below. Much of the information is just now being published in the latest Medical Journals so it truly is the latest medical information on the subject.
Propranolol is a widely prescribed medication classified as a beta-blocker used for the treatment of infantile hemangioma. Since 2007 it has been used off-label because there has not been an approved formulation of propranolol, specific for infants and the treatment of infantile hemangioma. Several institutions here in the USA and Europe have taken part in a 2+ year study assessing the safety of propranolol in infants. As a result an oral formulation will be available here in the USA in June 2014 under the brand name Hemangeol. (Pierre Fabre Pharmaceuticals USA will be manufacturing the medication) The studies have not only produced a new brand name of propranolol here in the USA but it has produced data on the safety and efficacy of this medication in the treatment of infantile hemangioma.
Oral Propranolol has a favorable risk profile in the pediatric population studied. In one study of 460 infants the IH improved in 88% of the patients treated with no unexpected safety concerns. This same group reported that patients tolerated the medication with mild or moderate side effects. The only contraindication being noted is bronchial reactivity. (1,2)
Another study examined the impact of propranolol on pediatric growth and human growth hormone levels in infants. No impact was found. (3)
A group from Russia studied the effects of propranolol on the cardiovascular system with and without preexisting heart problems. 154 infants with IH were prescribed propranolol and cardiological evaluation with EKG, ECHO, holter monitoring and blood pressure was observed for more then 9 months. Only a small percentage of adverse events were noted. This group recommends monitoring children at risk for cardiac complications during use of propranolol. A similar study out of Oregon concluded that routine ECG monitoring for patients prior to propranolol use is not necessary and a more purposed driven strategy is a better approach. (4,5)
272 Hemangioma Patients were evaluated for developmental psychomotor skills. No delays or effects on psychomotor development was found. (6)
In my review of this information propranolol appears to be safe to use in most infants and children presenting with infantile hemangioma. Patients should be monitored during treatment and physicians should be awear of the indications for concern. More studies are on going.
1.Christine Leaute-Labreze, Ilona Frieden, Pierre Vabres, Sorilla Prey, Jean-Jacques Voisard, Propranolol in IH: Results from an international randomized placebo controlled study.
2.Sorilla Prey, Christinen Leute-Labreze, Ilona Frieden, Allain Delarue, Jean Jacquez Voisard, Safety of oral propranolol for the treatment of IH: 2 years results of a controlled multicenter trial
3.Rachel Giese, Mario Cleves, Jessica Boswell, James Suen, Gresham Richter, Propranolol for Treatment of IH: Efficacy and Effect on Growth and Development
4. Margarita Timofeeva and Natalia Katlukova, Cardiovascular Complications of Propranolol Treatment for IH
5.Kevin Yarbrough, Alfan Krol, Julianne Mann, Sabra Leitenberger, Carol MacArthur, Is Routine ECG necessary prior to initiation of propranolol for treatment of IH
6. Andre Moyakine, Denise Hermans, Joris Fuijkschot, Carine van der Vleuten, Development Milestone: no negative effects detected upon psychomotor development
As these articles get published we will update the references and citations.
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NOVA Research Update
Infantile Hemangioma is the most common benign tumor o infancy and children. Although benign, patients diagnosed with IH often experience complications. It is often challenging for parents to determine if and when treatment is necessary. Many primary care physicians delay referral to physicians with experience in the diagnosis and treatment of IH based on the misconception that these lesions do not require treatment.
We have known for nearly 30 years that most infantile Hemangioma (IH) do not require medical intervention since they spontaneously regress in a process known as involution. Most of these lesions resolve to an acceptable state. However; a significant subset of Hemangioma patients do require treatment. Dr. Drolet and associates report that many patients experience complications including ulceration, bleeding, pain, visual impairment, airway impairment, residual scaring and permanent disfigurement. Dr. Frieden and associates have divided these complications into 3 categories as reasons to intervene.
- · Ulceration
- · Disfigurement
- · Impairment of function or vital structures
It is also noted that certain IH have a risk of structural anomalies which must be addressed.
Current research suggest s that the decision of if and when to intervene requires an understanding and “detailed knowledge” of the natural history of Hemangioma and the clinical indications of the increased risk. The data from recent studies reveal insights into the identification, evaluation and management of IH. The indication for treatment and the type of treatment; specifically medical treatments like corticosteroids, Beta-Blockers and Vincristine is revealed by Dr. Drolet’s recent publication.
NOVA Thanks all of the researchers and physicians dedicated to continuing the work to understanding the diagnosis and treatment of IH and other vascular anomalies. This work simplifies the decisions parents must make in seeking treatment for their child.
National Organization of Vascular Anomalies
1. Br J Dermatol. 2013 May 22. doi: 10.1111/bjd.12436. [Epub ahead of print], Hemangioma: Clinical Course, Complications, and Management. Luu M., Frieden IJ.
2. Am J Clin Dermatol. 2013 Apr;14(2):111-23. doi: 10.1007/s40257-013-0008-x., Infantile hemangiomas : an update.
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Ground-breaking technology to be used to study PHACE syndrome
Our laboratory and collaborators at the Medical College of Wisconsin/Children’s Hospital of Wisconsin are getting closer every day in our mission to identify the cause of PHACE syndrome. We are using whole genome sequencing to look for changes in genes that could cause PHACE syndrome. To successfully complete this work, we need to obtain more grant funding. Our grant will be much stronger if we have DNA from 100 families- that means getting a blood sample or buccal swab from both parents. We already have some initial results, but we can only make sense of these if we can compare the results to the parents’ DNA samples. In addition, the most helpful information is coming from tissue samples. If your child has any surgery for the revision of the hemangioma or aorta, please let us know!
Dawn Siegel, MD
Beth Drolet, MD
The PHACE syndrome Clinical Registry and Genetic Repository
Medical College of Wisconsin/Children’s Hospital of Wisconsin
Gene Identified in SWS and Port Wine Stains
After 25 years of searching, the Sturge-Weber Foundation (SWF) is thrilled to join patients, physicians, researchers and government agencies in celebrating the identification of the gene mutation responsible for Sturge-Weber syndrome and port-wine birthmarks. The new research was published online today in The New England Journal of Medicine. http://www.sturge-weber.org/