How is WBC function improved in patients with pediatric chronic granulomatous disease (CGD)?

Updated: Aug 07, 2019
  • Author: Lawrence C Wolfe, MD; Chief Editor: Cameron K Tebbi, MD  more...
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Answer

Based on preliminary observations suggesting the efficacy of interferon-gamma, a multi-institutional, randomized double-blind placebo-controlled study of interferon-gamma 50 mcg/m2/dose 3 times per week in patients with chronic granulomatous disease showed that it was well tolerated and that it reduced the frequency of serious infections. [18] The relative risk of a serious infection was 67% lower in the treated group than in the untreated group. Therapy seemed to benefit the youngest children the most.

Interferon-gamma does not correct or enhance phagocyte superoxide production in the vast majority of patients with chronic granulomatous disease. The exact mechanisms underlying the beneficial effect of interferon-gamma is not completely understood but most likely includes augmentation of oxidant-independent antimicrobial pathways. In a subset of patients with X91–chronic granulomatous disease, an increase in functional gp91 was produced.

Data have suggested that interferon-gamma partially corrects the oxidative burst defect in circulating phagocytes from patients with variant X-linked chronic granulomatous disease (X-CGD) or recessive chronic granulomatous disease. Induction of a dose-dependent increase in neutrophil aspergillicidal activity and FcgR1 expression are additional possible explanations for the beneficial role of interferon-gamma in chronic granulomatous disease.

Long-term interferon-gamma therapy was safe in a 9-year open-label study that concluded in 2001. [19] In that study, 76 patients (accounting for 328.4 patient-years) had no life-threatening event or delay in growth or development related to interferon-gamma. Adverse effects were reported by 38% of patients and included fever (most common event; treated with acetaminophen), headache, myalgias, fatigue, irritability, and flulike syndrome. Three (4%) of 76 patients withdrew from the study because of adverse effects. The study showed no increase in proinflammatory symptoms, such as granuloma formation or inflammatory bowel disease (IBD).

Interferon-gamma is now recommended as life-long therapy for infection prophylaxis in chronic granulomatous disease.


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