Chronic granulomatous disease as an SOS call for multicenter cooperative effort to prevent infections

Background Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disease. Patients with CGD experience recurrent life-threatening infections. Lack of large interventional trials generated several doubts for the treatment of infections in CGD. Objective To evaluate the effect of interferon gamma, antifungal drugs, and antibiotics in patients with CGD undergoing prophylaxis of infections. Methods A meta-analysis of the interventional trials was performed. The studies were identified by searching MEDLINE, ISI Web of Science, SCOPUS, and Cochrane database. The last search was run on January 2016. Reference lists of all studies included in the present systematic review were screened for potential additional eligible studies. Results Two studies with 163 patients with CGD were included in the interferon gamma analysis. Severe infections occurred in 17 of 73 patients (23%) treated with interferon gamma and in 49 of 90 patients (54%) not undergoing treatment with interferon gamma. Compared with control, severe infections were significantly reduced in patients treated with interferon gamma (relative risk, 0.46; 95% confidence interval, 0.29–0.73; P = .001). Interferon gamma treatment was associated with an absolute risk reduction of 31% and a number needed to treat of 3. Furthermore, compared with control, interferon gamma treatment reduced pulmonary infections (relative risk, 0.43; 95% confidence interval, 0.19–0.96; P = .04). Two studies with 172 patients with CGD were included in the antifungal drug analysis. Infections occurred in 4 of 69 patients (6%) treated with antifungals and in 17 of 103 patients (16%) not receiving treatment with antifungals. Compared with control, Aspergillus infections were not significantly reduced in patients treated with antifungals. No randomized prospective clinical trials of antibacterial prophylaxis in patients with CGD have been performed. Conclusion Despite the fact that interferon gamma prophylaxis seems to have a positive effect on severe infections, small sample sizes preclude definite conclusions. Further trials with interferon gamma and/or antifungal and antibiotics are necessary to optimize the treatment of CGD.