Clinical and biochemical effects of zileuton in patients with the Sjogren-Larsson syndrome

The Sjogren-Larsson syndrome (SLS) is an inborn error of lipid metabolism, characterised clinically by congenital ichthyosis, mental retardation and s pasticity. Patients also suffer from severe pruritus. The degradation of le ukotriene (LT) B-4 is one of the defective metabolic routes in SLS. Zileuto n inhibits the synthesis of LTB4 and the cysteinyl leukotrienes. Five SLS p atients were treated with zileuton for 3 months. Favourable effects were fo und on pruritus score (P = 0.006), general well-being, and background activ ity 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 cer ebral MRI and proton magnetic resonance spectroscopy did not change during therapy. Urinary concentrations of LTB4 and omega -OH-LTB4 decreased signif icantly (P=0.02 and P=0.003 respectively), while their concentrations in CS F were normal at baseline and remained so after therapy. Conclusion: patien ts with Sjogren-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 B-4 in the pathogenesis of pr uritus.