Infantile hemangioma - Role of Propranolol in its management

Introduction
Hemangiomas are common in children. It is seen in 1 in 10 of all children. About 50% of all hemangiomas in children are located in the head and neck area. Majority of them are single lesions which are inconspicuous at birth but undergoes rapid growth throughout the first year of life. Studies have also demonstrated that infantile hemanigomas are more common in premature infants. This has been attributed to the fact that mothers with premature uterine contractions receive tocolytics which are potential vasodilators.

Theories of infantile hemangioma:

1.Infantile hemangiomas have been postulated to originate from placenta – Studies have shown that endothelial cells constituting infantile hemangiomas resemble placental vessels
2.Mutation of endothelial cells
3.Environmental factors have been postulated to stimulate growth of these infantile hemangiomas

Regulators of hemangioma growth:

The topic of regulators involved in the growth and involution of infantile hemangiomas is still in infancy. Histologically infantile hemangiomas is composed of a mixture of clonal endothelial cells, pericytes, dendritic cells and mast cells.

Hemangiomas usually appears within the first few weeks of birth, undergoes rapid increase in size as the infant grows. The increase in size of infantile hemangiomas is much more rapid than that of infant's growth curve. This active proliferative phase is characterized histologically by plump endothelial cells showing evidence of frequent mitosis, increased number of mast cells and multilaminated basement membranes. Studies have demonstrated the involvement of two angiogenetic factors during this phase, they are basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). This phase of active proliferation is followed by a phase of spontaenous slow involution (possibly due to apoptosis). This phase is characterized histologically by the presence of flat inactive normal looking endothelial cells in a matrix of fibrofatty tissue.

Treatment modalities:

1.Oral steroids
2.Systemic steroids
3.Cyclophosphamide
Among the above three treatment modalities systemic steroids offer the best results, of course with its attendant complications. Intralesional steroid injections have caused significant reduction in the size of these masses.

Use of Propranolol in the management of infantile hemagiomas was noticed by accident when a few children who underwent treatment for their cardiopulmonary conditions with propranolol showed significant reduction in the size of the hemagiomatous lesions. This led to a flurry of activity in the medical world. Propranolol was discovered by Sir James Black. It is a non selective beta blocker which revolutionized cardiac and hypertension management for a long time.


Therapeutic effects of propranolol in hemangioma:

1.Vasoconstriction – The ability of this drug to cause constriction of blood vessels supplying hemangioma tissue will cause significant reduction in its size. The hemangioma also undergoes significant softening in response to propranolol
2.Down regulation of angiogenetic factors like bFGF and VEGF
3.Upregulation of apoptosis of capillary endothelial cells


Dosage:

Propranolol should be administered during the proliferative phase of infantile hemangiomas in doses of 2-3 mg /kg /day divided into 2-4 doses.

Precaution:

The drug should not be discontinued abruptly and should be done in a tapered manner (during the period of 2-3 weeks) to prevent rapid increase in the size of the lesion.