Simvastatin treatment for inflammatory attacks of the hyperimmunoglobulinemia D and periodic fever syndrome.
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.
Simon
Anna
A
Department of General Internal Medicine, University Medical Center St Radboud, Nijmegen, The Netherlands.
Drewe
Elizabeth
E
van der Meer
Jos W M
JW
Powell
Richard J
RJ
Kelley
Richard I
RI
Stalenhoef
Anton F H
AF
Drenth
Joost P H
JP
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
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D008798:Mevalonic Acid