Itraconazole to prevent fungal infections in chronic granulomatous disease

N Engl J Med. 2003 Jun 12;348(24):2416-22. doi: 10.1056/NEJMoa021931.


Background: Chronic granulomatous disease is a rare disorder in which the phagocytes fail to produce hydrogen peroxide. The patients are predisposed to bacterial and fungal infections. Prophylactic antibiotics and interferon gamma have reduced bacterial infections, but there is also the danger of life-threatening fungal infections. We assessed the efficacy of itraconazole as prophylaxis against serious fungal infections in chronic granulomatous disease.

Methods: Thirty-nine patients at least 5 years old (6 female and 33 male; mean age, 14.9 years) were enrolled in a randomized, double-blind, placebo-controlled study. After the initially assigned treatment, each patient alternated between itraconazole and placebo annually. Patients 13 years of age or older and all patients weighing at least 50 kg received a single dose of 200 mg of itraconazole per day; those less than 13 years old or weighing less than 50 kg received a single dose of 100 mg per day. The primary end point was severe fungal infection, as determined by histologic results or culture.

Results: One patient (who had not been compliant with the treatment) had a serious fungal infection while receiving itraconazole, as compared with seven who had a serious fungal infection while receiving placebo (P=0.10). No patient receiving itraconazole but five patients receiving placebo had a superficial fungal infection. No serious toxic effects were noted, although one patient had a rash and another had elevated results on liver-function tests; both of these effects resolved with the discontinuation of itraconazole.

Conclusions: Itraconazole prophylaxis appears to be an effective and well-tolerated treatment that reduces the frequency of fungal infections in chronic granulomatous disease, but monitoring for long-term toxic effects is warranted.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Antifungal Agents / adverse effects
  • Antifungal Agents / blood
  • Antifungal Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Granulomatous Disease, Chronic / complications
  • Granulomatous Disease, Chronic / drug therapy*
  • Humans
  • Itraconazole / adverse effects
  • Itraconazole / blood
  • Itraconazole / therapeutic use*
  • Male
  • Middle Aged
  • Mycoses / etiology
  • Mycoses / prevention & control*
  • Patient Compliance
  • Rare Diseases / drug therapy


  • Antifungal Agents
  • Itraconazole