Invasive Pulmonary Aspergillosis in a Young Adult With Hyperimmunoglobulin E Syndrome and Hypogammaglobulinemia Following Rituximab Therapy

Hyperimmunoglobulin E syndrome (HIES) is a rare primary immunodeficiency marked by elevated IgE levels, recurrent skin and pulmonary infections, and immune dysregulation. While typically diagnosed in childhood, adult presentations can occur, often complicated by structural lung disease, opportunistic infections, and malignancies. We report a 37-year-old female with signal transducer and activator of transcription 3 (STAT3)-deficient HIES, diffuse large B-cell lymphoma (DLBCL) in remission, rituximab-induced hypogammaglobulinemia, and recurrent infections, who presented with acute-on-chronic dyspnea. Imaging revealed a large cavitary lesion in the left upper lobe. Despite 30 days of appropriate antibiotics targeting methicillin-resistant Staphylococcus aureus (MRSA) and gram-negative organisms, her respiratory status deteriorated, necessitating intubation. Subsequent bronchoalveolar lavage and serum galactomannan testing confirmed invasive pulmonary aspergillosis (IPA) as the etiology of her deterioration, prompting combination antifungal therapy. This case highlights the importance of maintaining a broad differential diagnosis in immunocompromised patients with worsening respiratory symptoms despite antibiotics. Early consideration and testing for fungal infections in high-risk populations can prevent diagnostic delay and improve outcomes.