Propranolol Therapy for an Abdominal Giant Haemangioma in a Neonate

Address for correspondence: Dr. Martine KF Docx E-mail: docxmartine@skynet.be 1Docx MKF, Department of Paediatric Chronic Diseases and Hypertension, Queen Paola Children’s Hospital Antwerp Belgium, 2Vandenberghe P, Department of Paediatric Cardiology, Queen Paola Children’s Hospital Antwerp, Belgium, 3Van de Broek, Department of Neonatology, General Hospital Middelheim, Antwerp, Belgium, 4Govaert P, Department of Neonatology, General Hospital Middelheim Antwerp, Belgium. Abstract


Introduction
I nfan le haemangioma are benign vascular tumours, most of which resolve spontaneously and do not require treatment.Treatment is only indicated when complica ons are expected like impairment of vital func ons by ocular or airway involvement, and secondly in cases where the haemangioma cause signifi cant bleeding by fric on, ulcera on and disfi gurement.An increasing incidence with decreasing gesta onal age is described: 1-4% in term infants to 23% in those with a birth weight < 1000 g 1 .The serendipitous discovery in 2008 of propranolol, a non selec ve beta-adrenergic antagonist and a few years later the topical variant molol maleate 0.5%, has become the fi rst-line therapy for complicated haemangioma 2 .The la er resulted in a rapid replacement of oral steroids, laser surgery, interferon and vincris ne treatment.
The present case is a 1-day-old boy who presented to our neonatology department with a huge tuberous haemangioma of the en re right lower abdomen.A er relevant inves ga ons we decided to start oral propranolol therapy to prevent ulcera on and disfi gurement.

The Case
An one day of age a Moroccan boy was admi ed to our neonatal unit with a diagnosis of giant tuberous right abdominal haemangioma.The clinical examina on revealed no other vascular tumours.There was no evidence of heart failure.Ultrasound and MRA (Fig 1a-b) documented a giant vascular structure compa ble with haemangioma and with the following measurements: laterolateral diameter: 7 cm, anteroposterior diameter: 1.2 cm and craniocaudal diameter: 4 cm.The feeding vessel was the right common femoral artery and draining happened via the right common femoral vein.According to protocol for giant haemangioma we started with propranolol treatment at the age of three weeks.Baseline echocardiography together with a 12 lead ECG and 72-hr hospitalisa on was done to monitor vital signs and blood glucose levels.The results were normal.Propranolol was gradually tapered over a period of 2 weeks started with an ini al dose of 0.16 mg/kg body weight to up a maximum daily dose of 2 mg/kg (Fig 2).There were no side eff ects.A re-evalua on a er 7 days and then every month was done.We re-visualised the lesion with MRA a er four months of treatment, supplemented with monthly photographic documenta on, clinical examina on and ultrasound.(Fig 3-4)     The volume had strikingly diminished a er eight months therapy.Ultrasound of the lesion (Fig. 5 ): the craniocaudal diameter: 1.29 cm (max.) and 0.72 cm (min.).

Discussion
Haemangiomas are the most common tumours of infancy, especially in Caucasians, aff ec ng up to 12% of all children, occurring more frequently in girls with a sex ra o of 3:1.60% Of infan le haemangiomas are located in the head and neck region, 80% are single lesions 2,4,7 .They undergo rapid and intermi ent growth throughout the fi rst year of life.By the age of nine years 90% of the lesions have involuted, but nevertheless in 50% a residue can be observed (teleangiecta c cutaneous vessels, fi brous-fa y ssue, scar forma ons).There are diff erent theories on the origin of infan le haemangioma.These include sugges ons of placental origin, intrinsic defect or soma c endothelial muta on, and extrinsic factors crea ng a conduc ve milieu for growth.
Three hypotheses for the benefi cial eff ect of propranolol have been described 3,6,7 :-Vasoconstric on and thus almost immediate change and so ening of the lesions;

Triggering of apoptosis of capillary endothelial cells;
Decreased expression of vascular endothelial growth factor (VEGF) and basic fi broblast growth factor (bFGF) genes through downregula on of the RAFmitogen ac vated protein kinase pathway.
Most haemangiomata require no treatment, but it is impera ve if drama c aesthe c, and/or func onal impairment, like visual or airway obstruc on or ulcera on arises 7 .The response of infan le haemangioma to propranolol was published by Léauté-Labrèze et.al. 4,5,6 .

Conclusion
Propranolol is eff ec ve and safe for trea ng with a minimal dose to achieve involu on of 2 mg/kg/d.Treatment should only be reserved for lesions resul ng in signifi cant morbidity/mortality and disfi gurement.The dura on of the treatment should be maintained un l the lesion is involuted with an acceptable cosme c result.

Fig 1 :
Fig 1: a-b: MRA:Giant vascular structure.Fig. 1-b: Feeding vessel was the right common femoral artery and draining happened via the right common femoral vein (white arrow).

Fig 4 :
Fig 4: Minimal lesion a er nearly 8 months of treatment.

Fig 3 :
Fig 3: Regression of size a er nearly 4 months treatment.

Fig 5 :
Fig 5: Ultrasound of the lesion a er 8 months therapy.