title: Simvastatin treatment for inflammatory attacks of the hyperimmunoglobulinemia D and periodic fever syndrome.
abstract: Hyperimmunoglobulinemia D (hyper-IgD) and periodic fever syndrome, a hereditary autoinflammatory syndrome, is characterized by lifelong recurrent episodes of fever and inflammation. No effective treatment is known. It is caused by a defect of mevalonate kinase, an enzyme that follows 3'-hydroxy-3'-methylglutaryl-coenzyme A (HMG-CoA) reductase in the isoprenoid pathway. We wanted to test the hypothesis that inhibition of HMG-CoA reductase would ameliorate the inflammatory attacks. Six patients with hyper-IgD syndrome and proven mevalonate kinase deficiency were followed up for 2 treatment periods with either simvastatin, 80 mg/d, or placebo for 24 weeks, separated by a 4-week washout period in a double-blind fashion. Simvastatin resulted in a drop in urinary mevalonic acid concentration in all patients and decreased the number of febrile days in 5 of 6 patients. No side effects were observed. These data offer preliminary evidence for the hypothesis that simvastatin may improve inflammatory attacks in the hyper-IgD syndrome. This highlights the anti-inflammatory properties of HMG-CoA reductase inhibition.
authors.affiliation: Department of General Internal Medicine, University Medical Center St Radboud, Nijmegen, The Netherlands.
authors.forename: Anna
authors.initials: A
authors.lastname: Simon
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Drewe
authors.forename: Jos W M
authors.initials: JW
authors.lastname: van der Meer
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Powell
authors.forename: Richard I
authors.initials: RI
authors.lastname: Kelley
authors.forename: Anton F H
authors.initials: AF
authors.lastname: Stalenhoef
authors.forename: Joost P H
authors.initials: JP
authors.lastname: Drenth
mesh_terms: D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D010505:Familial Mediterranean Fever / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006942:Hypergammaglobulinemia / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008798:Mevalonic Acid / Q000652:urine; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D013577:Syndrome; D016896:Treatment Outcome
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D008798:Mevalonic Acid