Abstract
BACKGROUND: Autosomal dominant signal transducer and activator of transcription 3 (STAT3) mutations are broadly classified into loss-of-function (LOF) and gain-of-function (GOF) variants. LOF mutations in STAT3 are responsible for autosomal dominant hyperimmunoglobulin E syndrome (AD-HIES), a rare primary immunodeficiency disorder. This condition is characterized by elevated serum immunoglobulin E (IgE) levels, chronic eczema, and recurrent respiratory tract infections. Current conventional management strategies include antimicrobial therapy, immunoglobulin replacement, and systematic airway clearance. However, there remains a lack of targeted therapies specifically for AD-HIES, leading to substantial morbidity and significantly compromised quality of life for affected patients. Omalizumab, a monoclonal anti-human IgE antibody, is approved for the treatment of asthma and chronic spontaneous urticaria, but is rarely used in AD-HIES. Relevant studies on the application of omalizumab in AD-HIES patients primarily focus on alleviating skin issues, with significant improvements reported in most cases, but rarely focus on alleviating the lung symptom. We report two cases in which both skin and lung symptoms improved through a combination of omalizumab and conventional treatment. CASE DESCRIPTION: We report two cases of AD-HIES caused by STAT3 mutations, both complicated by pulmonary involvement. These two patients continued to experience frequent acute infections despite long-term antibiotic use, regular airway clearance, and other conventional treatments. We introduced omalizumab as an adjunct to their existing therapy. After 9 months of treatment, both their skin and lung symptoms were well controlled. The administration of omalizumab in combination with conventional therapy resulted in varying degrees of clinical improvement. CONCLUSIONS: The combination of omalizumab with conventional therapy may contribute to improved pulmonary and dermatological symptoms in patients with AD-HIES resulting from STAT3 LOF mutations.