Autosomal dominant loss of function mutation of signal transducer and activator of transcription 3 (STAT3) gene (STAT3-deficiency) predisposes to recurrent bacterial pneumonia that are complicated in 67% of patients with bronchiectasis, cavitations and Aspergillus infection or colonization in 22% of patients1. We aimed to report the prevalence, describe clinical, mycological, pathological and radiological presentation and both medical and surgical treatment of mold infections in the National French cohort.
Referent physicians of STAT3-deficient patients (n= 74 patients) were contacted to know if patients had evidence of colonization or infection with molds. Clinical and mycological information were collected and imaging was centralized. An expert committee reviewed all charts and classified the cases (EC, SP, CT, AD, FL, OL, MOC).
Eighteen episodes of filamentous fungal infection in ten (13.5%) STAT3-deficient patients were identified. The median age at first episode was 12 years (IQR 10.2-25). Ninety percent of patients had underlying pulmonary disease, bronchiectasis and cavitations, usually multiple. Mold infections were classified as follow: three aspergillomas, six Chronic Pulmonary Aspergillosis (CPA), five Allergic BronchoPulmonary Aspergillosis (ABPA), two mixed forms ABPA and CPA, one Chronic Allergic Sinus Aspergillosis and one Rasamsonia invasive pulmonary infection. According to EORTC/MSG definitions, no cases of invasive aspergillosis were reported. Aspergillus fumigatus was isolated in 13 cases, Rasamsonia argillocea in one case. Aspergillus precipitins were detectable in 86 % of cases (12/14).
Two-thirds of fungal episodes (12/18) were breakthrough infections (itraconazole prophylaxis in most cases), and half of the cases (9/18) occurred while on immunoglobulin substitutive therapy. First line antifungal therapy was voriconazole only (8/18) or amphotericin B alone or in association (6/18). Five patients required surgery (4 CPA, 1 aspergilloma). One patient died from respiratory failure at 11 years old.
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Mold infections occurred in 13.5% of STAT3-deficient patients from the French cohort, mostly on anatomical modification of the lung. Notably, patients developed aspergilloma, ABPA or CPA, but no invasive aspergillosis. Despite prolonged antifungal treatment and/or surgery half of the patients (5/10) relapsed.
Chandesris M-O et al. Autosomal Dominant STAT3 Deficiency and Hyper-IgE Syndrome: Molecular, Cellular, and Clinical Features From a French National Survey. Medicine (Baltimore). 2012 Jul;91(4):e1–19.