Simvastatin treatment for inflammatory attacks of the hyperimmunoglobulinemia D and periodic fever syndrome

Clin Pharmacol Ther. 2004 May;75(5):476-83. doi: 10.1016/j.clpt.2004.01.012.


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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Double-Blind Method
  • Familial Mediterranean Fever / drug therapy*
  • Familial Mediterranean Fever / pathology
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypergammaglobulinemia / drug therapy*
  • Hypergammaglobulinemia / pathology
  • Male
  • Mevalonic Acid / urine
  • Middle Aged
  • Simvastatin / administration & dosage
  • Simvastatin / therapeutic use*
  • Syndrome
  • Treatment Outcome


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Simvastatin
  • Mevalonic Acid