title: Educational paper: Pathogenesis of infantile haemangioma, an update 2014 (part I).
abstract: Infantile haemangioma (IH) is the most frequent childhood tumour. Although it is benign and self-limiting, severe complications can arise due to localisation and fast tumour growth. Management and therapy of IH has changed greatly after 2008 with propranolol. However, the pathogenesis remains elusive. This update provides an overview of all possible mechanisms currently considered. We discuss the possibility that several mechanisms act together, although local hypoxia seems to be important. Clinically, in about half of the cases, an IH is preceded by an anaemic macula (local ischaemia) or a so-called precursor lesion. Laboratory findings indicate stabilisation and an increased transcription activity of hypoxia-inducible factor 1 alpha (HIF1α), leading to up-regulation of its downstream target genes (such as vascular endothelial growth factor (VEGF)), which normally occurs in cases of hypoxia.
  
  
  CONCLUSIONS
  Three main hypotheses have been proposed, namely (1) the theory of tissue hypoxia, (2) the theory of embolization of placental endothelial cells and (3) the theory of increased angiogenic and vasculogenic activity.
authors.affiliation: Department of Paediatric Surgery, Erasmus University Medical Centre, Dr. Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands, s.janmohamed@erasmusmc.nl.
authors.forename: Sherief R
authors.initials: SR
authors.lastname: Janmohamed
authors.forename: Gerard C
authors.initials: GC
authors.lastname: Madern
authors.forename: Peter C J
authors.initials: PC
authors.lastname: de Laat
authors.forename: Arnold P
authors.initials: AP
authors.lastname: Oranje
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D018324:Hemangioma, Capillary / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007223:Infant; D009386:Neoplastic Syndromes, Hereditary / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D011433:Propranolol / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D011433:Propranolol