title: Clinical and biochemical effects of zileuton in patients with the Sjögren-Larsson syndrome.
abstract: The Sjögren-Larsson syndrome (SLS) is an inborn error of lipid metabolism, characterised clinically by congenital ichthyosis, mental retardation and spasticity. Patients also suffer from severe pruritus. The degradation of leukotriene (LT) B4 is one of the defective metabolic routes in SLS. Zileuton inhibits the synthesis of LTB4 and the cysteinyl leukotrienes. Five SLS patients were treated with zileuton for 3 months. Favourable effects were found on pruritus score (P = 0.006), general well-being, and background activity of electroencephalographic studies. Neuropsychological test results did not change significantly. There was, however, a clinically important trend towards improvement in the speed of information processing. Results of cerebral MRI and proton magnetic resonance spectroscopy did not change during therapy. Urinary concentrations of LTB4 and omega-OH-LTB4 decreased significantly (P=0.02 and P=0.003 respectively), while their concentrations in CSF were normal at baseline and remained so after therapy.
  
  
  CONCLUSIONS
  Patients with Sjögren-Larsson syndrome might benefit from treatment with zileuton, especially with respect to the agonising pruritus. The findings reported here, point to a crucial role for leukotriene B4 in the pathogenesis of pruritus.
authors.affiliation: Department of Paediatric Neurology, University Medical Centre St Radboud, Nijmegen, The Netherlands. m.willemsen@ckskg.azn.nl
authors.forename: M A
authors.initials: MA
authors.lastname: Willemsen
authors.forename: M A
authors.initials: MA
authors.lastname: Lutt
authors.forename: P M
authors.initials: PM
authors.lastname: Steijlen
authors.forename: J R
authors.initials: JR
authors.lastname: Cruysberg
authors.forename: M
authors.initials: M
authors.lastname: van der Graaf
authors.forename: M W
authors.initials: MW
authors.lastname: Nijhuis-van der Sanden
authors.forename: J W
authors.initials: JW
authors.lastname: Pasman
authors.forename: E
authors.initials: E
authors.lastname: Mayatepek
authors.forename: J J
authors.initials: JJ
authors.lastname: Rotteveel
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology; D004569:Electroencephalography; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use*; D016859:Lipoxygenase Inhibitors / Q000378:metabolism / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009483:Neuropsychological Tests; D016111:Sjogren-Larsson Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D016859:Lipoxygenase Inhibitors; C063449:zileuton; D006918:Hydroxyurea