135 Mycobacterial Infections in cChildren With Chronic Granulomatous Disease

BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte NADPH oxidase activity. Affected patients display severe, recurrent and multiple infections from the first year of life onwards, in particular caused by various pyogenic bacteria and fungi. Mycobacterial infections have more rarely been reported in these patients. METHODS: We examined the clinical features of mycobacterial disease in 59 CGD patients from 52 kindreds in 16 countries of 4 continents. Tuberculosis or BCG adverse reactions were identified by culture, staining, biopsy, polymerase chain reaction (PCR), and/or by a combination of clinical criteria with response to treatment. CGD was confirmed by NBT, DHR, cytochrome C reduction assay, or a combination of these. Genetic diagnosis was achieved by means of immunoblotting, flow cytometry, PCR and automated gene sequencing. RESULTS: We found that mycobacterial infections are fairly common in patients with CGD living in certain regions of the world. Twenty-four patients (45%) had tuberculosis, 43 (80%) presented with adverse effects shortly after Bacille Calmette-Guérin (BCG) vaccination; 12 of the patients (21%) had both tuberculosis infection and BCG adverse reactions. Most patients (93%) had also pyogenic and fungal infections; 7% of them, however, presented solely with mycobacterial disease. Most cases were one-time self-limited localized infections, but recurrence (13 patients, 20%), disseminated disease (18 patients, 30%) and even death (5 patients, 8%) were observed. A recurrent finding was early age of presentation for BCG reaction, with a median of 3 months of age; BCG disease was the first manifestation of immunodeficiency in 60% of these patients. CONCLUSIONS: Our study offers compelling evidence for an important susceptibility to mycobacterial diseases in patients with CGD, more easily noticed in countries where tuberculosis is endemic and BCG vaccine mandatory. BCG adverse reactions should raise the suspicion of CGD.