title: Diverse Cutaneous Presentations of Langerhans Cell Histiocytosis in Children: A Retrospective Cohort Study.
abstract: BACKGROUND
  Langerhans cell histiocytosis (LCH) is a rare disease, frequently affecting young children.
  
  
  METHODS
  We performed a retrospective study in patients younger than 16 years old manifesting with skin symptoms, and documented their different cutaneous lesions and systemic symptoms. We compared subgroups of children with single-system, skin-only, and multisystem disease and sought signs predictive for multisystem disease. In a small sample of patients, BRAF mutations were analyzed in archived biopsies.
  
  
  RESULTS
  A wide spectrum of cutaneous presentations varying from crusted nodules and papules, blisters, vascular tumor-like lesions, scaling orange to red macules (frequently in seborrheic regions) to purpuric macules, and papules was documented in our cohort of 32 children. Otitis externa was a common manifestation and mucosal lesions were seen in three patients. A novel manifestation was a red-blue nodule that appeared in a patient after a vaccination. None of the cutaneous lesions was predictive for the classification or final outcome as a single-system or multisystem disease. However, later onset and a more protracted course of skin lesions were more frequent findings in multisystem LCH. Mucosal lesions and otitis externa were almost exclusively seen in patients with multisystem disease, a finding that warrants further investigation. Both wild-type (WT) and mutated BRAF were found not only in multisystem LCH, but also in skin-only LCH. Two cases with rapidly resolving congenital lesions had WT BRAF.
  
  
  CONCLUSIONS
  Late onset and a protracted course of skin lesions are associated with MS-LCH, whereas WT BRAF is found in rapidly resolving skin lesions.
authors.affiliation: Department of Dermatology, University Hospitals Leuven, Leuven, Belgium and Department of Microbiology and Immunolgy KU Leuven, Belgium.
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Morren
authors.affiliation: Department of Dermatology, University Hospitals Leuven, Leuven, Belgium and Department of Microbiology and Immunolgy KU Leuven, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Vanden Broecke
authors.affiliation: Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Leen
authors.initials: L
authors.lastname: Vangeebergen
authors.affiliation: Department of Dermatology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Johannes Henk
authors.initials: JH
authors.lastname: Sillevis-Smitt
authors.affiliation: Department of Human Genetics, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Van Den Berghe
authors.affiliation: Department of Pathology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Esther
authors.initials: E
authors.lastname: Hauben
authors.affiliation: Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Jacobs
authors.affiliation: Laboratory of Pediatric Immunology, KU Leuven, Leuven, Belgium.
authors.forename: Stefaan W
authors.initials: SW
authors.lastname: Van Gool
mesh_terms: D005260:Female; D006646:Histiocytosis, Langerhans-Cell / Q000473:pathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011379:Prognosis; D012189:Retrospective Studies; D012867:Skin / Q000473:pathology*
keywords: BRAF; Langerhans cell histiocytosis; congenital self-healing reticulohistiocytosis; skin