title: Langerhans cell histiocytosis and Erdheim-Chester disease.
abstract: OBJECTIVE
  To provide an updated overview of the pathogenesis and treatment of Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD).
  
  
  RESULTS
  There is ongoing debate as to the exact pathogenesis of these disorders and their classification as reactive versus neoplastic. Proinflammatory cytokines are known to play a role in both LCH and ECD and strengthen the hypothesis that, at least in part, they are disorders of immune dysregulation. The recent discovery of activating mutations in the proto-oncogene BRAF in a subset of LCH patients suggests that LCH is in fact a neoplastic disorder. Understanding of the mechanisms that promote proliferation and migration of histiocytes has led researchers to explore targeted immune-modulatory therapies for ECD. Similarly for LCH, alternative chemotherapeutic agents and reduced-intensity hematopoietic stem cell transplant are being evaluated for refractory disease.
  
  
  CONCLUSIONS
  More research is needed to better understand the cause of these disorders and may help in identifying new targeted therapies, particularly for patients with refractory or relapsed disease. Multinational trials are ongoing for LCH and are urgently needed for ECD.
authors.affiliation: Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada. marta.wilejto@sickkids.ca
authors.forename: Marta
authors.initials: M
authors.lastname: Wilejto
authors.forename: Oussama
authors.initials: O
authors.lastname: Abla
mesh_terms: D031249:Erdheim-Chester Disease / Q000188:drug therapy / Q000209:etiology*; D006646:Histiocytosis, Langerhans-Cell / Q000209:etiology* / Q000628:therapy; D006801:Humans; D000090063:Proto-Oncogene Mas