Article Author:
Amal Chamli
Article Editor:
Noureddine Litaiem
4/10/2019 2:50:27 PM
PubMed Link:


Hemangiomas, also known as hemangiomas of infancy or infantile hemangiomas (IH), are the most common benign tumor of infancy.  [1] They are usually called "strawberry marks" because of their clinical appearance. They are a proliferation of endothelial cells. Infantile hemangiomas are angiomas and are characterized by early, rapid growth followed by spontaneous involution. They usually appear after birth in contrast to congenital hemangiomas which are visible at birth.


The etiology of infantile hemangiomas is poorly understood. But several hypotheses have been suggested. The most likely hypothesis involves hypoxic stress which upregulates expression of GLUT 1 and VEGF leading to the mobilization of endothelial progenitor cells CD133 + into CD31 positive cells.[2] Some authors suggest that placental trophoblast is a possible origin to stem cells.[3] Further authors support that IH development involves vasculogenesis from progenitor cells (de novo formation) as well as the formation of new vessels from existing ones (angiogenesis).[2] Angiogenic factors have been suggested to act on endothelial cells and pericytes to initiate the formation of a capillary network. Initially, this process is excessive, followed by an inhibition phase which is regulated by inhibitors of endothelial growth leading to regression of formed blood vessels.[4]


Infantile hemangioma is the most frequent noncancerous vascular tumor of infancy and affects about 4% to 5 % of newborns.[5] This abnormal cluster of small blood vessels occurs during the first year of life, usually after birth. Infantile hemangiomas occur more frequently in Caucasian infants compared to other racial groups. There is a female predominance with a female to male ratio of 2-5 to 1. Premature infants are more prone to develop hemangioma. Similarly, babies born with low birth weight or in the context of anterior or prenatal hypoxia may also develop hemangiomas. Infantile hemangioma is common in infants whose mothers are older. The disorder is often seen after post chorionic villus sampling or as part of multiple births as with twins and triplets. Most cases are sporadic but infantile hemangioma may run in families and has been linked to an autosomal dominant pattern of inheritance[6], but no specific genes are implicated.[7]


The histopathological examination shows proliferating of infantile hemangioma in a multinodular pattern fed by a single arteriole.[8] The nodules are composed of endothelial cell hyperplasia and pericytes with or without lumens; a prominent basement membrane is also seen. The involution stage is marked by dilated vascular lumens, flattened endothelial cells giving the IH a lobular architecture. Fibrosis becomes pronounced as involution progress.[9] Immunohistochemically, endothelial cells express CD31, von Willebrand factor, and urokinase in all phases. Infantile hemangioma expresses glucose transporter protein-1 (GLUT 1) during all phases of their development. Vascular endothelial growth factor (VEGF) expression predominates in the proliferating phase as well as proliferating cell nuclear antigen and type IV collagenase. In the involuting phase, infantile hemangioma expresses mostly tissue inhibitor of metalloproteinase which is reported to be an inhibitor of angiogenesis.[4] Placenta-associated vascular antigens staining, including FcRII, Lewis Y antigen (LeY) and merosin, is observed. Thus, immunohistochemical study can define the phenotype that could distinguish the different phases of hemangioma.

History and Physical

Infantile hemangioma is usually absent at birth but can present with several types of premonitory lesions such as a pale area of vasoconstriction, an erythematous macule, a telangiectatic red macule or blue bruise-like patches. Infantile hemangiomas become clinically apparent within 1 to 4 weeks. The localization is ubiquitous, and they may occur on the skin and mucosal surfaces. The majority present as a single localized cutaneous hemangioma but infantile hemangioma may be multifocal or segmental. Hemangiomas occur most commonly on the head and the neck in 60 % of cases, followed by the trunk in 25% of cases, and less commonly, the extremities in 15% of cases. [6] Hemangiomas can be superficial, deep or mixed composed of both superficial and deep components. Superficial lesions involve the superficial dermis and are raised lobulated and bright red. Deep hemangiomas, also called subcutaneous hemangioma, arise from the reticular dermis and/or subcutis and appear as a bluish-hued nodule, plaque or tumor. Mixed hemangiomas have features of both locations.

The natural history of infantile hemangioma has a triphasic evolution:

  • Early proliferative or growth phase: Usually rapid during the three first months and gradual growth during the first 6 to 8 months of life; deep infantile hemangiomas tend to proliferate for a longer period (until the ninth or 12th month of life). Infantile hemangioma tends to be firm and noncompressible.[3]
  • Plateau phase: The lesion remains stable and quiescent for a period of months (between 6 and 12 months of life).
  • Involution phase: May occur within the first year of life and can continue for several years. The regressive infantile hemangiomas become softer and more compressible, and the color changes from bright red to purple or gray. The skin may return to normal, but often there are residual changes (excessive fibrofatty tissue, telangiectasia, skin laxity).[3][7]


Most Infantile hemangiomas are usually diagnosed clinically. A skin biopsy can be performed in case of doubt – infantile hemangioma stain positively to GLUT 1. Imaging studies like ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI) are particularly indicated to confirm the diagnosis and extent of deep IH without superficial changes, to rule out associated anomalies and to differentiate proliferating IH from other tumors.

Treatment / Management

Most infantile hemangiomas do not require treatment because they usually regress on their own. Complicated infantile hemangioma requires treatment. Recently beta blockers like oral propranolol are used as the first line therapy because of it effectiveness; the usual dose is 2 mg/kg per day. Serious adverse effects of propranolol include bradycardia, hypotension, bronchospasm, and hypoglycemia. Oral prednisone is an alternative therapy in case of a contradiction of propranolol and is given at a dose of 2 to 4 mg/kg per day. The high dose is slowly tapered over weeks to months. Adverse reactions are common and include irritability, sleep disturbance, hypertension, bone demineralization, cardiomyopathy, and growth retardation. Intralesional and topical corticosteroids can be used to treat small focal lesions. [3] Topical beta blocker timolol is used for smaller superficial and uncomplicated infantile hemangioma.

Surgical excision may be considered for focal hemangioma to prevent complications; one removes the residual fibrofatty tissue which improves treatment outcomes.

Pulsed dye laser (PDL) is indicated for telangiectasia or but PDL remains controversial for infantile hemangioma with a deep component.[10]

Differential Diagnosis

  • Congenital hemangioma
  • Pyogenic granuloma
  • Kaposiform hemangioendothelioma
  • Tufted hemangioma
  • Venous malformation
  • Capillary malformation: port wine stain
  • Macrocystic lymphatic malformation
  • Malignant tumors: sarcoma, a cutaneous location of neuroblastoma, lymphoma


The prognosis is very good for noncomplicated IH with complete involution in the majority of cases. 50% of hemangiomas resolve in 5 years, 70% by 7 years and 90% by 9 years. Approximately 8% of IH leave cosmetic disfigurement and require some intervention.


The complications depend on the age of the child, localization, and size of the hemangioma. Complications of IH include:

  • Ulceration: The most common complication occurs in up to 10%, locations with higher risk include the anogenital, lower lip, axilla, and neck.
  • Ophthalmologic complications include amblyopia, astigmatism, myopia, retrobulbar involvement and tears duct obstruction.
  • Airway obstruction: Nasal, subglottic and laryngeal obstruction.
  • Feeding difficulty: Perioral or lip hemangiomas.
  • Visceral hemangiomatosis: Multifocal hemangiomas (greater than or equal to 5 skin lesions) may be associated with liver or gastrointestinal involvement.
  • Cosmetic disfigurement: nasal tip (Cyrano nose), ear, perioral, lip, large facial.
  • PHACES syndrome: Large segmental facial hemangioma (greater than or equal to 5 cm) are associated with PHACES syndrome (acronym of Posterior fossa malformations, Hemangioma of the cervicofacial region, Arterial anomalies, Cardiac anomalies, Eye anomalies, and Sternal or abdominal clefting or ectopia cordis).[3]
  • LUMBAR syndrome: Lumbosacral hemangiomas may be associated with underlying developmental anomalies: LUMBAR syndrome (acronym of Lumbosacral hemangioma, Urogenital anomalies, Myelopathy, Bony deformities, Anorectal and arterial, and Renal anomalies).[3]

Enhancing Healthcare Team Outcomes

The key goal is preventing or reversing life or function-threatening complications of IH as well as the prevention of permanent cosmetic disfigurement that may have a psychosocial impact on the patient and the family.

The management of IH is best done with a multidisciplinary approach including a team of pediatricians, dermatologist, ophthalmologist, and other specialists. Besides, physicians must first determine whether treatment is indicated. The treatment must be carefully weighed against potential benefits.


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[2] Yu Y,Flint AF,Mulliken JB,Wu JK,Bischoff J, Endothelial progenitor cells in infantile hemangioma. Blood. 2004 Feb 15;     [PubMed PMID: 14576053]
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[4] Takahashi K,Mulliken JB,Kozakewich HP,Rogers RA,Folkman J,Ezekowitz RA, Cellular markers that distinguish the phases of hemangioma during infancy and childhood. The Journal of clinical investigation. 1994 Jun;     [PubMed PMID: 7911127]
[5] Léauté-Labrèze C,Harper JI,Hoeger PH, Infantile haemangioma. Lancet (London, England). 2017 Jul 1;     [PubMed PMID: 28089471]
[6] Bruckner AL,Frieden IJ, Hemangiomas of infancy. Journal of the American Academy of Dermatology. 2003 Apr;     [PubMed PMID: 12664009]
[7] Margileth AM,Museles M, Cutaneous hemangiomas in children. Diagnosis and conservative management. JAMA. 1965 Nov 1;     [PubMed PMID: 5897362]
[8] TOMPKINS VN,WALSH TS Jr, Some observations on the strawberry nevus of infancy. Cancer. 1956 Sep-Oct;     [PubMed PMID: 13364872]
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[10] Stier MF,Glick SA,Hirsch RJ, Laser treatment of pediatric vascular lesions: Port wine stains and hemangiomas. Journal of the American Academy of Dermatology. 2008 Feb;     [PubMed PMID: 18068263]