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Infantile Hemangioma

  • Author: Richard J Antaya, MD; Chief Editor: William D James, MD  more...
 
Updated: Apr 24, 2015
 

Practice Essentials

Infantile hemangiomas are benign vascular neoplasms that have a characteristic clinical course marked by early proliferation and followed by spontaneous involution. Hemangiomas are the most common tumors of infancy and usually are medically insignificant. See the image below.

This proliferating superficial infantile hemangiom This proliferating superficial infantile hemangioma on the trunk required no therapy.

See 13 Common-to-Rare Infant Skin Conditions, a Critical Images slideshow, to help identify rashes, birthmarks, and other skin conditions encountered in infants.

Signs and symptoms

Infantile hemangiomas may be cutaneous or extracutaneous. Frequency of cutaneous hemangiomas at particular sites is as follows:

  • Head and neck - 60%
  • Trunk - 25%
  • Extremities - 15%

Sites of extracutaneous hemangiomas include the following:

  • Liver
  • Gastrointestinal tract
  • Larynx
  • Central nervous system
  • Pancreas
  • Gallbladder
  • Thymus
  • Spleen
  • Lymph nodes
  • Lung
  • Urinary bladder
  • Adrenal glands

Cutaneous hemangiomas progress sequentially through the following stages:

  • Blanching of the involved skin
  • Occasionally (especially with lip and buttock lesions), a shallow ulceration
  • Fine telangiectasias
  • A red or crimson macule or papule, often surrounded by a faint halo of vascular blanching

Features are as follows:

  • Usual maximum size 0.5-5 cm
  • Range from the size of a pinhead to greater than 20 cm in diameter
  • Most remain well circumscribed and focal
  • A minority are segmental in nature and more extensive

Infantile hemangiomas characteristically exhibit early rapid growth followed by slow involution, as follows[1, 2, 3, 4] :

  • Rapid growth during the neonatal period (birth to 4 wk) is the historical hallmark of infantile hemagiomas
  • The hemangioma becomes elevated and dome shaped, lobulated, plaquelike, tumoral, or any combination of these morphologies
  • The most growth occurs during the first 4-6 months of life
  • Proliferation slows considerably between 6-12 months of life
  • Complete involution in 50% of infantile hemangiomas by age 5 years and 70% by age 7 years
  • Complete involution may take an additional 3-5 years in the remainder

See Clinical Presentation for more detail.

Diagnosis

Skin biopsy can be performed if the diagnosis is in question after a thorough history and physical examination. Infantile hemangiomas uniformly stain positively for glucose transporter 1 (GLUT-1) during both the proliferation and the involution phases.

The following laboratory studies have been investigated as possible markers of hemangioma proliferation and differentiation[5, 6] :

  • Serum and urinary vascular endothelial growth factor (VEGF)
  • Urinary beta-fibroblast growth factor
  • Urinary matrix metalloproteinases (MMPs)

Magnetic resonance imaging (MRI) has the following uses:

  • Delineate the location and extent of cutaneous and extracutaneous hemangiomas
  • Differentiate proliferating hemangiomas from other high-flow vascular lesions (eg, arteriovenous malformations)

Features of ultrasonography:

  • Can help differentiate hemangiomas from other deep dermal or subcutaneous structures, (eg, cysts, lymph nodes)
  • Cannot fully evaluate the magnitude and extent of the hemangioma
  • High vessel density (>5 vessels/cm 2) and high peak arterial Doppler shift (>2 kHz) are sensitive and specific for infantile hemangiomas, as compared with other soft tissue masses [7]

See Workup for more detail.

Management

The vast majority of infantile hemangiomas do not require any medical or surgical intervention.[8] Treatment options for clinically significant hemangiomas include the following:

  • Laser surgery
  • Surgical excision
  • Medication

Features of laser surgery:

  • Flashlamp-pumped pulsed-dye laser most widely used
  • Pulsed-dye laser surgery effective for treating ulcerated hemangiomas and thin superficial hemangiomas
  • Lasers used especially on areas likely to result in significant functional or psychological impact (eg, fingers, eyes, lips, nasal tip, ears, face) [9, 10]
  • Many ulcerated hemangiomas respond with decreased pain (sometimes as early as a few days after the initial treatment), rapid reepithelialization, and hastened involution
  • Laser treatments generally performed every 2-4 weeks until complete healing results
  • Scarring or residual skin changes may occur
  • Laser treatment may worsen ulceration, particularly of deep or combined superficial and deep lesions

Features of surgical excision:

  • Not uncommonly used for correction of cutaneous defects from involuted hemangiomas [11]
  • Specially trained surgeons needed for surgical excision of proliferating hemangiomas because of the risk of hemorrhage and damage to vital structures
  • Early excision may save life, preserve vision, or eliminate a cosmetically disfiguring lesion

Features of pharmacologic treatment:

  • Corticosteroids can slow the growth and decrease the size of proliferating infantile hemangiomas
  • Oral corticosteroids preferred over intralesional injection
  • Propranolol has become the treatment of choice for disfiguring or functionally significant hemangiomas [12] ; an expert panel recently developed provisional recommendations for the use of propranolol in complicated infantile hemangioma [13, 14]
  • The FDA has approved an oral pediatric formulation of propranolol hydrochloride (Hemangeol) for the treatment of proliferating infantile hemangioma requiring systemic therapy

See Treatment and Medication for more details.

Next

Background

Infantile hemangiomas are benign vascular neoplasms that have a characteristic clinical course marked by early proliferation and followed by spontaneous involution. During the proliferative phase in the neonatal period or early infancy, a rapidly dividing endothelial cell proliferation is responsible for the enlargement of infantile hemangiomas. Finally, an involutional phase occurs, whereby most infantile hemangiomas are clinically resolved by age 9 years.

Hemangiomas are the most common tumors of infancy, and most infantile hemangiomas are medically insignificant. Occasionally infantile hemangiomas may impinge on vital structures, ulcerate, bleed, cause high-output cardiac failure or significant structural abnormalities or disfigurement. Rarely, a cutaneous infantile hemangioma may be associated with one or more underlying congenital anomalies.

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Pathophysiology

Infantile hemangiomas are composed of proliferating, plump endothelial cells. Early in proliferation, the cells are in disarray, but, with time, they form vascular spaces and channels replete with blood cells (see image below).

Histopathology of a proliferating infantile hemang Histopathology of a proliferating infantile hemangioma with plump endothelial cells in the dermis.

These benign-appearing endothelial cells produce limited basement membrane structures. Hemangiomas assume a lobular architecture as proliferation slows and ends. Mast cells appear to affect this process and are implicated in the promotion of feeding arterioles and veins that supply each lobule. They also have been found in high concentrations during involution.

Takahashi hypothesized that during the third trimester of fetal development, immature endothelial cells coexist with immature pericytes, which maintain their proliferative capacity for a limited period during postnatal life.[12] Angiogenic peptides, such as beta-fibroblast growth factor, vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen, induce proliferation of these immature cells, resulting in the development of the hemangioma. As the endothelial cells differentiate, an influx of mast cells, various myeloid cells, and tissue inhibitors of metalloproteinases (TIMPs) occurs.[15] TIMPs, along with interferon and transforming growth factor produced by the mast cells, terminate the endothelial cell proliferation and passively induce involution by senescence of endothelial cells.

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Mortality/Morbidity

Most infantile hemangiomas are benign and do not cause any morbidity or mortality. Occasionally, they may impinge on vital structures and interfere with breathing, vision, eating, or hearing. Ulceration of certain areas (eg, diaper area, neck, mucosal surfaces) is not uncommon. Excessive bleeding is infrequent and rarely, if ever, life threatening. In the past, infantile hemangiomas were confused with other vascular neoplasms, particularly kaposiform hemangioendothelioma and tufted angiomas, which can incite a consumptive coagulopathy that may be life threatening. This is referred to as Kasabach-Merritt phenomenon (KMP). It is now generally accepted that infantile hemangiomas are rarely, if ever, responsible for KMP.[16, 17]

Large cutaneous or visceral hemangiomas (particularly liver) can result in high-output cardiac failure resulting from increased vascular flow. Permanent significant structural abnormalities may result, particularly when facial structures are involved. The highest risk appears to be with involvement of the nasal tip, lips, and ears.[18] Segmental hemangiomas, which cover a particular section or area of skin, may be markers for underlying malformations or developmental anomalies of the heart, blood vessels, or nervous system (PHACE and PELVIS syndromes [see below] and lumbosacral hemangiomas) and, depending on the severity of the associated anomaly, can result in increased morbidity or mortality.[19, 20]

PHACE syndrome (see image below) is posterior fossa structural brain abnormalities (Dandy-Walker malformation and various forms of hypoplasia); hemangiomas of the face, head, and neck (segmental, >5 cm in diameter); arterial lesions (especially carotid, cerebral, and vertebral); cardiac anomalies (coarctation of the aorta in addition to many other structural anomalies); eye abnormalities; and, rarely, associated midline ventral defects such as sternal cleft or supraumbilical raphe). A consensus statement with detailed diagnostic criteria for both PHACE and possible PHACE syndromes was published in 2009.[21]

Segmental infantile hemangioma in a female infant Segmental infantile hemangioma in a female infant with PHACE syndrome involving the posterior neck and right forehead associated with an absent right vertebral artery and a laryngeal hemangioma.

PELVIS syndrome (see image below) is perineal hemangioma with any of the following: external genital malformations, lipomyelomeningocele, vesicorenal abnormalities, imperforate anus, and/or skin tags.

Segmental infantile hemangioma with minimal or arr Segmental infantile hemangioma with minimal or arrested growth of the bilateral buttocks and posterior thigh in this male infant with PELVIS syndrome (complicated by cutaneous ulceration, hypospadias, anal stenosis, intraspinal lipoma with tethered cord). The white material is a barrier diaper cream.

 

Content.

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Epidemiology

United States

Infantile hemangiomas occur in approximately 1-2% and 10% of white infants at birth and at age 1 year, respectively.[3, 4] African American and Japanese infants have a similar incidence of 1-2% at birth; however, there are no studies regarding the incidence at age 1 year (the actual incidence since the majority are not present at birth) in other nonwhite populations.[4, 22] The incidence of infantile hemangiomas is approximately 22-30% of preterm infants with birthweight less than 1 kg; for preterm infants with birthweight greater than 1.5 kg,[23] the incidence is the same as for term infants. An increased incidence is recognized in infants from multiple gestations.

The incidence is increased with older maternal age, maternal placenta previa, and preeclampsia.[24] Some, but not all, surveys have demonstrated increased incidence in infants born to mothers who have undergone prenatal chorionic villus sampling.

Race

Hemangiomas occur most commonly in white infants, with an incidence rate 10-12 times that of black and Asian infants.

Sex

Females are affected more often than males by a ratio of 3:1. This disparity is higher (9:1) in those infants with large cervicofacial segmental hemangiomas associated with PHACE syndrome.

Age

Thirty percent of infantile hemangiomas are present at birth, and 70% of them initially appear in the first several weeks of life.

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Contributor Information and Disclosures
Author

Richard J Antaya, MD Director of Pediatric Dermatology, Professor, Departments of Dermatology and Pediatrics, Yale University School of Medicine

Richard J Antaya, MD is a member of the following medical societies: American Academy of Dermatology, Society for Pediatric Dermatology, American Academy of Pediatrics

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Van Perry, MD Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Van Perry, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Jean Paul Ortonne, MD Chair, Department of Dermatology, Professor, Hospital L'Archet, Nice University, France

Jean Paul Ortonne, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

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Histopathology of a proliferating infantile hemangioma with plump endothelial cells in the dermis.
This proliferating superficial infantile hemangioma on the trunk required no therapy.
Exquisitely painful ulcerated mixed hemangioma (superficial and deep) of the left deltoid in a 6-month-old female infant. This lesion was treated successfully with pulsed dye laser.
This superficial and deep infantile hemangioma resulted in astigmatism of the left eye, requiring spectacles to correct the refractive error and to prevent amblyopia. Further growth of this hemangioma necessitated a course of oral prednisolone. The hemangioma shrunk rapidly, and the patient's astigmatism decreased such that the spectacles were unnecessary 1 month after beginning steroids.
Segmental infantile hemangioma in a female infant with PHACE syndrome involving the posterior neck and right forehead associated with an absent right vertebral artery and a laryngeal hemangioma.
Segmental infantile hemangioma with minimal or arrested growth of the bilateral buttocks and posterior thigh in this male infant with PELVIS syndrome (complicated by cutaneous ulceration, hypospadias, anal stenosis, intraspinal lipoma with tethered cord). The white material is a barrier diaper cream.
 
 
 
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