Clinical Features of Adults Aged 50 and Older with STAT3DN Hyper IgE Syndrome

Backgrounds and Aims Hyper IgE syndrome (HIES) resulting from dominant negative STAT3 (STAT3DN) mutations is a multisystem disease where pulmonary infections and complications are recognized as a cause of disability and mortality. Comorbidities for patients with STAT3 DN HIES include hypertension, chronic pain, and depression, which can lead to disruption of daily activities and contribute to decreased quality of life. The aim of this project is to describe the clinical features and disease burden of older patients with STAT3 DN HIES. Methods We retrospectively reviewed patients with STAT3 DN HIES, identifying 18 patients aged 50 years or older (9 male, 11 living, median age 56 years). Fifteen patients (83%) had parenchymal lung abnormalities with 6 (33%) requiring oxygen. Thirteen patients (72%) had decreased 6-minute walk distances, which was compounded by chronic pain, which was seen in 10 patients (55%). Three patients had joint replacement and seven had other orthopedic surgeries. 14 (78%) had osteoporosis/osteopenia. Other comorbid conditions include significant gastrointestinal bleeding (5), reflux (12), history of cancer—lymphoma (2), lung (1), thyroid (1), and skin cancer (2). Hearing loss is documented in 9 patients. Eleven patients (61%) take medication for anxiety, depression, or sleep disturbance. Causes of death include pneumonia, respiratory failure, sepsis, lung cancer, and suicide. Conclusions With earlier age of diagnosis, aggressive treatment for pulmonary infections, and availability of antifungal agents, people with STAT3 DN HIES may live longer with fewer complications of pulmonary disease. However, this population is medically complicated and has risk factors for cardiovascular disease, bleeding, fractures, and malignancy. There is significant musculoskeletal disease that often leads to chronic pain and decreased mobility. Further study of the vascular and musculoskeletal complications of this disease is needed to improve survival and quality of life. Funded by the NCI Contract No. 75N91019D00024.