Invasive Mould Infections in Chronic Granulomatous Disease: A Multicenter Study From Türkiye

Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency, predisposing to life-threatening invasive mould infection (IMI). While antifungal prophylaxis has improved outcomes, IMI remains the leading cause of mortality in CGD. This study aimed to evaluate the clinical and fungal epidemiology of IMI among CGD patients in Türkiye and explore diagnostic and treatment challenges.

Demographics, clinical characteristics, IMI episodes, diagnostic methods, and antifungal prophylaxis regimens of 72 CGD patients followed at the Division of Paediatric Immunology of Marmara, Cerrahpaşa and Çukurova University School of Medicine, Türkiye between 1991 and 2022 were analysed. IMI episodes were classified as proven, probable, or possible based on the European Organisation for Research and Treatment of Cancer/Mycoses Study Group criteria.

Of the patients, 79.1% were male, and 52.8% had autosomal-recessive CGD (AR-CGD). Forty-two IMI episodes were detected in 39 (54.2%) patients, predominantly involving the lungs. Proven IMI accounted for 28.5% of episodes, with Aspergillus fumigatus as the most frequent pathogen. Patients with X-linked CGD experienced earlier IMI onset than AR-CGD (34.0 months (IQR: 18.0-65.5) versus 122.0 months (IQR: 40.25-240.0; p = 0.005)). Presentation with IMI led to the CGD diagnosis in 20 (51.3%) patients, while 19 (48.7%) developed IMI under itraconazole prophylaxis (median: 96.0 months, IQR: 48.0-153.0). Of 13 deaths (18.0%), 84.6% were associated with IMI.

Our study highlights the persistently high burden of IMI among CGD patients, despite antifungal prophylaxis. Challenges in diagnosis, including limited access to invasive biopsy and diagnostic modalities, and gaps in prophylactic monitoring, underscore the need for optimised management strategies.