Novel STAT3 Mutation in a Patient with Hyper-IgE Syndrome Presenting with Recurrent Pulmonary Infections (Job Syndrome)

Background: Autosomal dominant hyper-IgE syndrome (AD-HIES), caused by signal transducer and activator of transcription 3 (STAT3) mutations, is a rare primary immunodeficiency disorder characterized by recurrent eczema-like rashes, skin and pulmonary abscesses, and significantly elevated serum IgE levels. The purpose of this article is to highlight the distinct clinical presentation, the importance of genetic studies in diagnosing AD-HIES, and the role of bronchoscopy lavage in managing pulmonary complications. Case report: Herein, we report a 9-year-11-month-old girl of Chinese origin who presented with recurrent eczema-like rashes, fingertip abscesses, and recurrent pulmonary infections. In her past medical history, she experienced severe allergies to seafood and peanuts, and frequent infections such as congenital pneumonia, recurrent bacterial and viral pneumonia, and cutaneous abscesses. The immunological workup revealed normal T cells, B cells, and natural killer cells (TBNK) panel, normal general immunology results, and an increase in IgE level > 5000 IU/mL. The genetic testing confirmed a heterozygous STAT3 mutation (autosomal dominant) while the National Institutes of Health (NIH) AD-HIES score was 45 (>40, highly suggestive of Job Syndrome). She underwent extensive immunological and genetic workups, including STAT3 expression testing via flow cytometry, which showed normal expression despite the detected pathogenic variant. Bronchoscopy lavage was performed as part of her pulmonary infection management, which was preferred over surgical intervention. Conclusion: Further studies on STAT3 mutations are required to better understand genotype-phenotype correlations in HIES. Bronchoscopy lavage should be considered over invasive procedures for managing pulmonary infections in pediatric patients with HIES.