Treatment of Infantile Haemangioma

Also known as a strawberry naevus, an infantile haemangioma is a proliferative benign tumour affecting the cutaneous blood vessels, in which the endothelial cells lining the vessels proliferate in an overgrowth manner. A haemangioma may be superficial, deep, or mixed (both superficial and deep). The pathogenesis is yet to be fully defined, but it is thought that they arise as a result of foetal hypoxia, in which endothelial progenitor cells (EPCs) responding to hypoxia cause new blood vessels to form. Usually EPCs are gone by the time a baby is born but they may still be present in premature or low birth-weight babies, leading to the development of haemangiomas. It is likely that the disappearance of EPCs as the child matures leads to the regression of haemangiomas.

Infantile haemangiomas may not be present at birth and usually develop within the first one to three weeks of life, with the vast majority (> 80%) developing on the head or neck. Initially the area may only have a few superficial blood vessels visible, but as the vessels divide and multiply the area becomes a noticeable bright strawberry red colour. The proliferation is rapid in the first three months, with growth usually slowing or stopping by five months; however, haemangiomas may continue to grow for up to 18 months in some cases. Once growth halts the haemangioma naturally starts to slowly involute and disappear, a process that may take up to 10 years in some cases. In at least half of cases involving larger ‘bulky’ haemangiomas there may not be complete regression and a scar, excess skin, or telangiectasia may remain.

In contrast, other types of birth mark, for example capillary vascular malformations (also known as port-wine stains), are present and visible at birth and are unlikely to improve without treatment.

Haemangiomas are considered the most common of the benign tumours that occur in infants. Up to 10% of neonates develop one or more infantile haemangiomas, affecting girls more commonly than boys (ratio of 2:1). In addition to gender other risk factors include prematurity, birth weight less than 1kg, multiple gestation, white skin and advanced maternal age. No genetic component has been identified for developing haemangiomas, but a family history is considered by some sources as an additional risk factor.

An infant’s GP or paediatrician should be made aware of the presence of a haemangioma, regardless of location, for assessment since the treatment of haemangioma requires specialist involvement. While some haemangiomas cause no problems to the infant and will resolve without issue, some require urgent referral (see Table 1) as they are more likely to be associated with complications and may require treatment.

Table 1. Haemangiomas that require urgent referral

The decision to treat infantile haemangiomas is based on location, size and complexity. When deciding to treat, the risks and benefits should be carefully considered, and in many cases (particularly if a haemangioma is not on the face or in another high-risk area) treatment is not required. Treatment may be considered for haemangiomas that: are in close proximity to important structures (for example the eyes, ears, nose, or airways), become ulcerated, or pose a risk to the child’s self-esteem or social development.

Currently available treatments include medication, surgery or laser therapy. Medicines that are most commonly used include beta-blockers such as oral propranolol or topical timolol, or corticosteroids. Other potential therapies include sirolimus, vincristine, imiquimod, interferon alpha, and angiotensin-converting enzyme inhibitors, but these agents have less evidence and safety data to support their use.

Oral propranolol is considered first-line treatment for patients that require systemic therapy, but the complex mechanism of action for haemangioma resolution is yet to be fully understood. Consensus guidelines recommend that propranolol is initiated in healthy infants at a dose of 1mg/kg/day split over two doses, which can be increased to 2mg/kg/day after one week if required. In high-risk infants, for example if the infant has a low body weight or has a risk of hypoglycaemia, a lower initiation dose of 0.5mg/kg/day may be given in a setting in which the heart rate and blood glucose level may be monitored for the first three hours after initiation. Side effects that have been reported with the use of oral propranolol for this indication include hypotension, bradycardia, cold extremities, hypoglycaemia, bronchospasm, diarrhoea, and sleep disturbances. It is recommended that propranolol is administered with food, and it should be withheld if the child has a decreased food intake or if they develop an illness.

In the past, oral or intralesional corticosteroids were considered first line therapy; however, corticosteroid use has fallen out of favour in preference for propranolol. Propranolol was shown to be more efficacious when compared to corticosteroids in a 2016 meta-analysis and is considered to have a preferable safety profile. Systemic steroids may be considered for patients who are unable to use beta-blockers, such as those with bradycardia or asthma.

A systematic review and meta-analysis conducted in 2017 investigated the efficacy and adverse effects of using topical timolol preparations. Researchers found that most studies used timolol 0.5% applied topically to the area twice daily, although preparation strength varied between studies from 0.1% to 0.5%. Low participant numbers in the included studies (N = 691) resulted in an inability to draw sound conclusions regarding the comparative efficacy between the studied timolol strengths, but pooled meta-analysis for timolol 0.5% indicated a 91% resolution rate compared to 9% in patients receiving placebo or no treatment. It was found that the incidence of side effects was relatively low and that the preparations were well tolerated, however, researchers noted that this is based on a low number of participants and that participant selection bias may have affected results. Researchers concluded that the results of the analysis appear to support the use of topical timolol, but recommended that it be reserved for superficial, small, uncomplicated haemangiomas until more evidence is available.

Whilst most infantile haemangiomas are harmless and will resolve over time, it is important that infants with one or more suspected haemangiomas are referred promptly for review, specialist referral, and treatment if necessary.