Xie Tiange, Xu Na, Zhao He, Han Yingdong, Wu Juan, Di Hong, Peng Min, Zhang Ting, Fan Hongwei, Zhang Yun, Zeng Xuejun
Department of Family Medicine & Division of General Internal Medicine, Department of Internal Medicine. Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, State Key Laboratory of Complex Severe and Rare Diseases Peking, Union Medical College Hospital, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
Department of Pulmonary and Critical Care Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China.
Orphanet J Rare Dis. 2025 Jun 3;20(1):270. doi: 10.1186/s13023-025-03749-6.
The hyper-IgE syndromes (HIES) are a heterogeneous group of inborn errors of immunity-sharing manifestations including increased infection susceptibility, eczema, and raised serum IgE. Pulmonary complications are responsible for high morbidity and mortality rates in patients with HIES. This study examines the progression of pulmonary disease in adult patients with HIES and compares the subsequent findings with existing literature.
Ten adult patients with HIES diagnosed at Peking Union Medical College Hospital (PUMCH) from January 2016 to October 2023 were included in this study. Diagnosis was confirmed using the National Institutes of Health (NIH) criteria and whole-exome sequencing. Clinical data on pulmonary disease progression, microbiology, imaging and histology were collected. A systematic literature review was conducted for comparison.
Recurrent pulmonary infections led to significant structural lung damage, with 90.0% (9/10) of patients developing bronchiectasis and pneumatocele. Early infections (0-10 years) were predominantly due to Staphylococcus aureus (80.0%,8/10), while later stages (6-22 years) showed a shift to more complex infections with Aspergillus/fungus (70.0%,7/10), Mycobacterium tuberculosis (50.0%, 5/10), and Pseudomonas aeruginosa (40.0%, 4/10). Imaging revealed extensive bronchiectasis and pneumatocele formation. Histological examinations demonstrated acute inflammation (40%, 2/5), granuloma formation (80%, 4/5), and eosinophilic infiltration (100%, 5/5). Comparatively, our findings are consistent with previous reports that suggest a higher incidence of pulmonary structural damage in patients with the signal transducer and activator of the transcription 3 (STAT3) mutations than in those with other gene variants. However, our cohort showed a faster progression from initial infection to structural damage, highlighting the need for early intervention.
The progression of pulmonary disease in HIES patients underscores a critical three-step process: initial recurrent infections, development of structural lung damage, and subsequent reinfections that aggravate the damage. This rapid transition from infection to structural damage, especially in patients with STAT3 mutations, highlights the importance of early and aggressive intervention. Managing reinfections after structural lung damage is essential to prevent further deterioration and to improve long-term outcomes.
高免疫球蛋白E综合征（HIES）是一组异质性的先天性免疫缺陷疾病，具有包括感染易感性增加、湿疹和血清免疫球蛋白E升高在内的共同表现。肺部并发症是导致HIES患者高发病率和死亡率的原因。本研究探讨成年HIES患者肺部疾病的进展情况，并将后续结果与现有文献进行比较。
本研究纳入了2016年1月至2023年10月在北京协和医院（PUMCH）确诊的10例成年HIES患者。诊断采用美国国立卫生研究院（NIH）标准和全外显子测序进行确认。收集了关于肺部疾病进展、微生物学、影像学和组织学的临床资料。进行了系统的文献综述以作比较。
反复肺部感染导致显著的肺部结构损伤，90.0%（9/10）的患者出现支气管扩张和气囊肿。早期感染（0 - 10岁）主要由金黄色葡萄球菌引起（80.0%，8/10），而后期（6 - 22岁）则转变为更复杂的感染，包括曲霉/真菌（70.0%，7/10）、结核分枝杆菌（50.0%，5/10）和铜绿假单胞菌（40.0%，4/10）。影像学显示广泛的支气管扩张和气囊肿形成。组织学检查显示急性炎症（40%，2/5）、肉芽肿形成（80%，4/5）和嗜酸性粒细胞浸润（100%，5/5）。相比之下，我们的研究结果与先前的报告一致，即与其他基因变异的患者相比，信号转导和转录激活因子3（STAT3）突变的患者肺部结构损伤的发生率更高。然而，我们的队列显示从初始感染到结构损伤的进展更快，突出了早期干预的必要性。
HIES患者肺部疾病的进展强调了一个关键的三步过程：初始反复感染、肺部结构损伤的发展以及随后加重损伤的再感染。这种从感染到结构损伤的快速转变，特别是在STAT3突变的患者中，凸显了早期积极干预的重要性。在肺部结构损伤后管理再感染对于防止进一步恶化和改善长期预后至关重要。
