Spectrum of pulmonary aspergillosis in Hyper IgE syndrome with autosomal dominant STAT3 deficiency.

BACKGROUND: Autosomal dominant signal transducer and activator of transcription 3 (STAT3) deficiency predisposes to recurrent bacterial pneumonia, complicated by bronchiectasis and cavitations. Aspergillosis is a major cause of morbidity in these patients. However, its diagnosis, classification, and treatment are challenging.

OBJECTIVE: We aimed to assess the prevalence and describe the clinical, mycological, and radiological presentation and related therapy and outcome of Aspergillus infections of the respiratory tract in the STAT3 deficient patients of the National French cohort.

METHODS: We performed a retrospective study of all pulmonary aspergillosis cases in STAT3 deficient patients (n=74). Clinical and mycological data were collected up to October 2015 and imaging was centralized.

MAIN RESULTS: Twenty-one episodes of pulmonary aspergillosis in 13 (17.5%) STAT3deficient patients were identified. The median age at first episode was 13 years (IQR 10-26). Ninety percent of patients had previous bronchiectasis or cavitations. Infections were classified as follows: five single aspergilloma, nine chronic cavity pulmonary aspergillosis (CCPA), five allergic broncho-pulmonary aspergillosis-like disease (ABPA-like), and two mixed forms of concomitant ABPA-like and CCPA. No invasive aspergillosis cases were identified. Aspergillus sp. were isolated in 71% of episodes and anti-Aspergillus antibodies in 93%. Eleven episodes were breakthrough infections. Antifungal treatment was prolonged with a median of 13 months and six patients (seven episodes) required surgery with a high rate of post-surgical complications. One patient died and six relapsed.

CONCLUSION: Chronic and allergic forms of aspergillosis occurred in 17.5% of STAT3 deficient patients, mostly in lung cavities. Almost half had recurrences, despite prolonged antifungal treatment and/or surgery.