title: Differentiating skin-limited and multisystem Langerhans cell histiocytosis.
abstract: OBJECTIVE
  To identify features associated with multisystem involvement and therapeutic failure in patients with skin Langerhans cell histiocytosis (LCH).
  
  
  METHODS
  We reviewed medical records of 71 consecutive patients with LCH with skin involvement evaluated at Texas Children's Hospital and analyzed clinical features, laboratory results, and the presence of circulating cells with the BRAF-V600E mutation with respect to initial staging and clinical outcomes.
  
  
  RESULTS
  Skin disease in patients older than 18 months of age at diagnosis was associated with the presence of multisystem disease (OR, 9.65; 95% CI, 1.17-79.4). Forty percent of patients referred for presumed skin-limited LCH had underlying multisystem involvement, one-half of these with risk-organ involvement. Patients with skin-limited LCH had a 3-year progression-free survival of 89% after initial therapy, and none developed multisystem disease. Patients with skin/multisystem involvement had a 3-year progression-free survival of 44% with vinblastine/prednisone therapy, and risk-organ involvement did not correlate with failure to achieve nonactive disease. Circulating cells with BRAF-V600E were detected at higher frequency in patients with multisystem involvement (8 of 11 skin/multisystem vs 1 of 13 skin-limited; P = .002).
  
  
  CONCLUSIONS
  Skin-limited LCH necessitates infrequent therapeutic intervention and has a lower risk of progression relative to skin plus multisystem LCH. The less-aggressive clinical course and lack of circulating cells with the BRAF-V600E mutation in skin-limited LCH suggest a different mechanism of disease origin compared with multisystem or risk-organ disease.
authors.affiliation: Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX. Electronic address: sjsimko@txch.org.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Simko
authors.affiliation: Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Garmezy
authors.affiliation: Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.
authors.forename: Harshal
authors.initials: H
authors.lastname: Abhyankar
authors.affiliation: Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Lupo
authors.affiliation: Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.
authors.forename: Rikhia
authors.initials: R
authors.lastname: Chakraborty
authors.affiliation: Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.
authors.forename: Karen Phaik Har
authors.initials: KP
authors.lastname: Lim
authors.affiliation: Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.
authors.forename: Albert
authors.initials: A
authors.lastname: Shih
authors.affiliation: Department of Pathology, Baylor College of Medicine, Houston, TX.
authors.forename: M John
authors.initials: MJ
authors.lastname: Hicks
authors.affiliation: Pediatric Dermatology Service, Baylor College of Medicine, Houston, TX.
authors.forename: Teresa S
authors.initials: TS
authors.lastname: Wright
authors.affiliation: Pediatric Dermatology Service, Baylor College of Medicine, Houston, TX; Pediatric Dermatology Service, Dell Children's Medical Center, Austin, TX; Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Moise L
authors.initials: ML
authors.lastname: Levy
authors.affiliation: Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: McClain
authors.affiliation: Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.
authors.forename: Carl E
authors.initials: CE
authors.lastname: Allen
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006646:Histiocytosis, Langerhans-Cell / Q000175:diagnosis* / Q000628:therapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D012871:Skin Diseases / Q000175:diagnosis* / Q000628:therapy; D016019:Survival Analysis; D013781:Texas