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Background Infantile haemangioma (IH) has recently been reported as an aberrant proliferation and differentiation of a primitive mesoderm-derived haemogenic endothelium regulated by the renin-angiotensin system (RAS), leading us to propose angiotensin converting enzyme (ACE) as a potential therapeutic target. Objectives To present initial results of our open-labelled observational clinical trial using captopril, an ACE inhibitor (ACEi), in the treatment of problematic proliferating IH. Methods After initial screening investigations, infants with problematic IH were admitted for initiation of captopril with a 0·1 mg kg−1 test dose orally, followed by 0·15 8-hourly over 24 h. This was then followed by dose escalation to 0·3 mg kg−1 8-hourly for another 24 hours. The dosage was increased to 0·5 mg kg−1 8-hourly 1 week later, if a noticeable involution had not already occurred. The response of IH to captopril was documented clinically and photographically before and after treatment and any side-effect was recorded. Results Two boys and six girls aged 5-22 weeks (mean 12·9) with problematic IH were recruited with the lesions located in nasal tip ( n = 1), cervicofacial ( n = 3), periorbital ( n = 1) and perineal ( n = 2) areas, and shoulder ( n = 1). Transient mild renal impairment occurred in one subject but resolved spontaneously. No other complication was observed. The IHs in all patients responded to captopril at a dosage of 1·5 mg kg−1 daily which led to a dramatic response in three, moderate response in two, and slow response in three patients. Continued involution of IHs was observed during the follow-up period of 8-19 months (mean 15·8) in all subjects. Treatment was ceased at 14 months of age in seven patients with no rebound growth. In the remaining patient, rapid healing occurred with ongoing gradual reduction in the size and colour of a large ulcerated retroauricular lesion following 5·5 months of treatment. The lesion was excised to address its persistent distortion of the ear. Conclusions The response of IH to an ACEi supports a critical role for the RAS in IH and represents a paradigm shift in the understanding and treatment of this enigmatic condition. [ABSTRACT FROM AUTHOR]

Infantile haemangioma (IH) is a tumour of the microvasculature composed predominantly of proliferating endothelial cells. It expresses markers associated with endothelial, haematopoietic and mesenchymal lineages. We have previously shown that the cells forming the capillary endothelium of proliferating IH express cell surface markers and transcriptions factors consistent with it being a haemogenic endothelium. We wished to determine whether the expression of transcription factors associated with the erythroid lineage was of physiological relevance and sufficient for IH tissue cultured in vitro to undergo erythropoiesis. Immunohistochemical staining of paraffin-embedded sections of proliferating IHs was undertaken and expression of the embryonically associated haemoglobin ζ (HBZ) chain and the erythropoietin receptor (EPO-R) was determined. Relative expression of mRNA encoding these proteins was determined by quantitative reverse transcription-polymerase chain reaction using snap-frozen biopsy samples. Differentiation towards erythrocytes was investigated using freshly resected tissue cultured as explants in Matrigel. The endothelium of the microvessels, but not the pericyte layer, was strongly immunoreactive for the EPO-R and the embryonically associated HBZ chain. Abundant expression of transcripts encoding these proteins was also detected, corroborating the immunohistochemical staining. When tissue was grown in culture the cells emanating from IH explants were able to generate enucleated erythrocytes in vitro. The erythrocytes were immunoreactive for the erythrocyte-specific marker glycophorin A. The microvessels in IH are a functional haemogenic endothelium that expresses the embryonically associated HBZ chain and is able to form erythrocytes in vitro. IH thus represents a possible extramedullary site for tumour-associated primitive erythropoiesis. [ABSTRACT FROM AUTHOR]