Spectrum of Pulmonary Aspergillosis in Hyper-IgE Syndrome with Autosomal-Dominant STAT3 Deficiency

Abstract

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.

Results: Twenty-one episodes of pulmonary aspergillosis in 13 (17.5%) STAT3-deficient patients were identified. The median age at first episode was 13 years (interquartile range, 10-26 years). Ninety percent of patients had previous bronchiectasis or cavitations. Infections were classified as follows: 5 single aspergilloma, 9 chronic cavity pulmonary aspergillosis, 5 allergic bronchopulmonary aspergillosis-like disease, and 2 mixed forms of concomitant allergic bronchopulmonary aspergillosis-like disease and chronic cavity pulmonary aspergillosis. No invasive aspergillosis cases were identified. Aspergillus species 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 6 patients (7 episodes) required surgery, with a high rate of postsurgical complications. One patient died and 6 had a relapse.

Conclusions: 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.

Keywords: Allergic bronchopulmonary aspergillosis; Aspergilloma; Aspergillosis; Cavitary chronic pulmonary aspergillosis; STAT3-deficient patient.