Infantile hemangiomas (IHs), in other words ”strawberry birthmarks” are spongy, raised naevi on the skin, usually with a soft, red surface. In Caucasian race they occur in 1 in 20 babies (1), whereas the incidence in Asian and black children reaches about 1% (2). They are more common in females and premature infants (3). Still only 30% of infantile hemangiomas are present at birth (1). Most of them develop in the first weeks of life. Studies show that up to 80% of lesions will have regressed by the age of 7(1). Generally in most cases the “wait and see” approach seems to be the best, but sometimes the treatment is vital. Due to the recurring complications of hemangiomas or strong interference with daily function doctors decide to intervene. Yet the best treatment option has not been established.
The pathogenesis of IH is poorly understood. There is evidence that the tumor shares some antigens with human placenta, but the mechanism of its development is not clear. The most popular and through classification of vascular birthmarks was proposed by the International Society for the Study of Vascular Anomalies (ISSVA) in 1996 (4). It recognizes two major group of vascular birthmarks – vascular malformations and vascular tumors. The distinction between these two is based on the histologic appearance, cellular markers (such as GLUT-1) and natural history.
IH is the most common vascular tumor of infancy, others are rather rare. It is characterized by rapid growth and subsequent slow spontaneous involution. On the contrary vascular malformations grow proportionately to the child and usually do not resolve themselves. Salmon patch, port wine stains and telengiectasia are the examples. Radiological examination of the birthmarks helps differentiate between them mainly with use of Doppler sonography, MR or arteriogram. However, in many clinics patients suspected of hemangioma do not undergo these diagnostic procedures.
Interestingly, according to the ISSVA classification infantile hemangioma is not associated with any of the genetic syndromes except for the PHACE. Syndromes such as Sturge-Weber, Klippel-Trenaunay or Beckwith-Wiedemann are characterized by various vascular malformations, but not hemangiomas, as it is sometimes suggested. Many clinicians use the histologic division of hemangiomas into capillary or cavernous. However, they seldom order biopsies but base on their clinical experience. Whatever the classification may be, the neonatologists rarely start the diagnostic procedures due to the hope that the mark will resolve itself in time.
Which cases exactly is the treatment important in? Hemangioma is by definition benign. It can be classified into three morphological subtypes: superficial, deep and combined. The superficial IH occurs in approximately 60% of cases (5). However, all lesions might be associated with ulceration, heavy bleeding and infection. These complications increase the risk of scarring. Considering the fact that the majority of hemangiomas is cutaneous and localized on the face, the intensive growth of the birthmark may cause severe disfigurement. Therefore it can negatively affect the child’s psychosocial development and distress the parents. Such unfortunate localization as an eye lid may cause potentially irreversible vision impairment.
Hemangiomas may appear extracutaneously. When placed in a mouth, or precisely on the mucosa of subglottic area, they might debilitate the function of breathing and feeding. In such cases the treatment is needed to provide the patient with the best conditions for proper development. Sometimes hemangiomas occur in the upper airways and may cause symptoms of airway obstruction. Approximately 10-25% of infants with hemangiomas have multiple hemangiomas. Studies show that 5 or more cutaneous hemangiomas might be a threshold for ultrasound screening for visceral hemangioma (6). Disease known as diffuse neonatal hemangiomatosis is a serious condition which can be associated with high-output congestive heart failure, visceral bleeding and hydrocephalus. Untreated patients have a high mortality rate thus the treatment should be introduced immediately. Interestingly, large or visceral IHs may be co-morbid with hypothyroidism due to the special metabolism of a tumor. But as the screening test for hypothyroidism is obligatory for all neonates, it rarely causes diagnostic problems.
According to the latest 2011 Cochrane Review there are several approaches to the treatment of problematic hemangiomas (7). The first-line treatment of 2-3mg/kg/day of prednisolone may be used during the proliferating phase. It is proved to slow down the growth of a tumor and even cause the shrinkage of a mass. The duration of treatment varies accordingly to the response, which is good in only 30% of cases. Moreover, adverse effects of steroids do discourage the clinicians and parents. Intralesional and topical use of corticosteroids has been proposed, but only for small, localized IHs.
Other treatment options include interferone-α, especially for life-threatening hemangiomas that did not respond to corticosteroids. Interferone-α is not a promising agent due to significant neurotoxicity. Other pharmaceuticals mentioned in literature and applicable to hemangioma patients are: intravenous vincrisitine, topical imiquimod and intralesional bleomycin. Nowadays they are mostly abandoned. The use of propranolol seems to be the new hope for problematic hemangioma and recently has become the second-line treatment. Some authors see propranolol as the first choice therapy (8).
For the drug – resistant hemangiomas surgical intervention is suitable. The early excision is indicated only for a small subset of hemangiomas, which include periorbicular tumor or painful chronically ulcerated hemangioma. Furthermore, the use of pulsed dye laser (PDL) is recommended for superficial lesions. Unfortunately it frequently causes atrophic scarring. Cryotherapy or radiation are rarely used, whereas arterial embolization is employed to treat life-threatening hemangiomas in order to reduce the high cardiac output.
As we see the subject of IH is very broad and surely worth pediatricians’ and general practitioners’ attention. In spite of the fact that the vast majority of infantile hemangiomas will regress, the rest will cause diagnostic and therapeutic problems. Although a research into the treatment of hemangioma has recently gathered speed, firstly clinicians need to know what they are looking at. The more we know about the disease the better health care we can provide for the youngest patients.
1.Current Paediatrics 1999;9(1):20-6. Vascular birthmarks: update on presentation and management..Syed SB
2.Journal of the Formosan Medical Association 1993;92(9):838-41. Birthmarks and congenital skin lesions in Chinese newborns. Tsai FJ, Tsai CH. .
3.Lancet 1959;2(7111):1057-9.. Natural history of cavernous haemangiomata. Simpson JR
4.Neonatal Dermatology textbook by Lawrence F. Eichenfield, Nancy B. Esterly, Ilona J. Frieden. (Chapter ‘’Vascular Stains, Malformations and tumors’’ by Odile Enjolras and Maria C.Garzon) 2nd edition, published January 2008, Elsevier Health Sciences
5.Curr Probl Pediatr. 1996 Jan;26(1):3-39.Cutaneous hemangiomas, vascular stains and malformations, and associated syndromes.Esterly NB.
6.Pediatr Dermatol. 2011 May-Jun;28(3):245-53. doi: 10.1111/j.1525-1470.2011.01420.x. Epub 2011 Apr 26.Prospective study of the frequency of hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas. Horii KA et al
7.Leonardi-Bee J, Batta K, O’Brien C, Bath-Hextall FJ. Interventions for infantile haemangiomas (strawberry birthmarks) of the skin. Cochrane Database of Systematic Reviews 2011, Issue 5. Art. No.: CD006545. DOI: 10.1002/14651858.CD006545.pub2.
8.Pediatr Dermatol. 2011 Oct 13. doi: 10.1111/j.1525-1470.2011.01569.x. [Epub ahead of print] Propranolol Therapy in 55 Infants with Infantile Hemangioma: Dosage, Duration, Adverse Effects, and Outcome. Schupp CJ, Kleber JB, Günther P, Holland-Cunz S
Do you want to know more about hemangioma? Watch on medtube.net: Cavernous hemangioma in the armpit