Long-term itraconazole prophylaxis against Aspergillus infections in thirty-two patients with chronic granulomatous disease,☆☆,

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Abstract

We conducted a prospective, open study of oral itraconazole therapy (5 and then 10 mg/kg per day) to assess tolerance and potential efficacy in preventing fungal infections in patients with chronic granulomatous disease. Thirty-two patients were enrolled in one center between 1985 and 1991. Tolerance was excellent in all cases. Poor compliance was suspected in three cases. Two patients were excluded from efficacy analysis because itraconazole was used as part of therapy for pulmonary aspergillosis. Of 30 patients, 3 developed a fungal (Aspergillus) lung infection, an incidence 3.4/100 patient-years versus 11.5 in a historical control group that did not receive any prophylaxis (p = 0.13) and 9.55 in a historical group of patients who received daily ketoconazole prophylaxis (p = 0.19). The percentage of patients infected with Aspergillus was significantly different: 10% in the itraconazole group versus 34.4% in the untreated group (p = 0.013). These results require further evaluation through a comparative randomized trial to assess the possible benefit of itraconazole prophylaxis in patients with chronic granulomatous disease. (J PEDIATR 1994;125:998-1003)

Section snippets

Patients

Every patient with CGD who was followed at Hôpital des Enfants Malades, Paris, was included in this trial. The diagnosis of CGD was based on personal and family history and confirmed by laboratory tests: defective reduction of nitroblue tetrazolium, impaired bacterial killing, absence of stimulated oxygen consumption, absence of superoxide formation, impaired chemiluminescence production by neutrophils, and absence of granulocyte cytochrome b559. The mode of inheritance was determined according

Efficacy of itraconazole prophylaxis

A fungal pulmonary infection was observed in five patients. In two patients, aspergillosis occurred within 4 months after interruption of curative treatment by amphotericin B. One of them had pulmonary chest wall and subcutaneous involvement treated with amphotericin B for 4 months; the infection was not completely healed when prophylaxis with itraconazole was begun at a dosage of 5 mg/kg per day. The other boy had been treated with amphotericin B (7 months), and the aspergillosis recurred

DISCUSSION

Ingestion of itraconazole is well tolerated; the known adverse drug reactions include gastrointestinal disturbances, headache, and diarrhea. Hypokalemia and increased serum liver enzyme values have been reported,20, 21 as have three cases of hepatitis.22 Our results are in accordance with these findings. A wider clinical experience is needed to confirm the absence of hepatic toxic effects during long-term treatment of children, because ketoconazole-induced hepatitis appears to be idiosyncratic.

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    From the Unité d'Immunologie et d'Hématologie and Unité d'Endocrinologie Pédiatrique, Hôpital des Enfants Malades, Paris, and the Laboratoires Janssen, Campus de Maigremont, Val de Reuil, France.

    ☆☆

    Reprint requests: Richard Mouy, MD, Unité d'Immunologie et d'Hématologie, Hôpital des Enfants Malades, 149, rue de Sèvres, 75743 Paris Cedex 15, France.

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