Consecutive non-Aspergillus Fungal Invasive Infections in Chronic Granulomatous Disease: Data from the French National Reference Center for Primary ImmunoDeficiencies and literature review

BACKGROUND: Non-Aspergillus invasive fungal infections (NAFI) are increasingly reported in patients with Chronic Granulomatous Disease (CGD), but precise clinical descriptions remain scarce. OBJECTIVE AND METHODS: We conducted a retrospective analysis of NAFI cases among CGD patients in the French National Registry of Primary Immunodeficiencies (CEREDIH) and in a comprehensive literature review. RESULTS: We identified 16 proven NAFI (9 molds, 6 yeasts and 1 Pneumocystis) among 263 CGD patients from CEREDIH and included an additional 106 probable/proven NAFI from a literature review (75 molds, 29 yeasts, 1 Pneumocystis, 1 dimorphic). Mold NAFI occurred at a median age of 17 years [IQR 9-23], and were mostly located to the lungs (79%, 65/82). Mold NAFI were breakthrough in 59% of patients (35/59), and 24% were receiving immunosuppressive treatments (13/54, mostly high-dose corticosteroids, n = 11). Lung surgical biopsies yielded the highest diagnostic rate (39/39) compared to less invasive methods (BAL 8/18 and transthoracic punctures 8/12). Nine patients with mold NAFI, including 3 refractory cases, were cured after Hematopoietic Stem Cell Transplantation (HSCT). Overall mortality for mold NAFI was 25% (20/81). Yeast infections occurred at a median age of 5 years [IQR 0-13], and 36% were receiving immunosuppressive treatments (5/14, mostly anti-TNF agents, n = 4). Infections were frequently located to lymph nodes or lungs, and 64% (21/33) were disseminated. Two yeast NAFI were cured after HSCT. Mortality was 26% (7/27). CONCLUSION: NAFI in CGD patients are frequently severe, often occur despite prophylaxis and under additional immunosuppression, commonly require invasive procedures for diagnosis, and may be effectively managed with HSCT.