Tang Xiaolei, Shen Yuelin, Zhou Chunju, Yang Haiming, Liu Hui, Li Huimin, Liu Jinrong, Zhao Shunying
The Second Department of Respiratory Medicine Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China.
Department of Pathology Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China.
Pediatr Investig. 2019 Dec 21;3(4):201-206. doi: 10.1002/ped4.12162. eCollection 2019 Dec.
Surfactant protein C (SP-C) dysfunction is a rare disease associated with interstitial lung disease. Early therapies may improve outcomes but the diagnosis is often delayed owing to variability of manifestations.
To investigate the manifestations and outcomes of SP-C dysfunction.
We retrospectively analyzed the records of five pediatric patients who were diagnosed with SP-C dysfunction between February 2014 and April 2017 at Beijing Children's Hospital.
The five patients included two boys and three girls with a median age at diagnosis of 1.3 years. All patients presented with interstitial lung disease and had a heterozygous mutation, including an I73T mutation in three patients, a V39L mutation in one patient, and a Y104H mutation in one patient. In addition to common respiratory manifestations, hemoptysis and anemia were observed in one patient with the I73T mutation. Elevated levels of autoantibodies and a large number of hemosiderin-laden macrophages in bronchoalveolar lavage fluid were found in two patients with the I73T mutation, suggesting the presence of diffuse alveolar hemorrage and autoimmunity. Chest high-resolution computed tomography features included ground-glass opacities, reticular opacities, cysts, and pleural thickening. Transbronchial lung biopsy was performed in one patient with the I73T mutation, which revealed the presence of some hemosiderin-laden macrophages in alveolar spaces. All patients received treatment with corticosteroids; two received combined treatment with hydroxychloroquine. During follow-up, the two patients who received hydroxychloroquine showed improved symptoms; of the remaining three patients, two died after their families refused further treatment, while the final patient was lost to follow-up.
This is the first report to describe a new phenotype of diffuse alveolar hemorrhage with autoimmunity in patients with I73T mutation. Treatment with hydroxychloroquine should be considered for patients with SP-C dysfunction.
表面活性物质蛋白C（SP-C）功能障碍是一种与间质性肺疾病相关的罕见疾病。早期治疗可能改善预后，但由于临床表现的变异性，诊断往往延迟。
研究SP-C功能障碍的临床表现和预后。
我们回顾性分析了2014年2月至2017年4月在北京儿童医院被诊断为SP-C功能障碍的5例儿科患者的病历。
5例患者包括2名男孩和3名女孩，诊断时的中位年龄为1.3岁。所有患者均表现为间质性肺疾病，且有杂合突变，其中3例患者为I73T突变，1例患者为V39L突变，1例患者为Y104H突变。除常见的呼吸道表现外，1例I73T突变患者出现咯血和贫血。2例I73T突变患者支气管肺泡灌洗液中自身抗体水平升高，并有大量含铁血黄素巨噬细胞，提示存在弥漫性肺泡出血和自身免疫。胸部高分辨率计算机断层扫描特征包括磨玻璃影、网状影、囊肿和胸膜增厚。1例I73T突变患者接受了经支气管肺活检，结果显示肺泡腔内存在一些含铁血黄素巨噬细胞。所有患者均接受了皮质类固醇治疗；2例接受了羟氯喹联合治疗。随访期间，接受羟氯喹治疗的2例患者症状改善；其余3例患者中，2例在其家属拒绝进一步治疗后死亡，最后1例患者失访。
这是首份描述I73T突变患者出现伴有自身免疫的弥漫性肺泡出血新表型的报告。对于SP-C功能障碍患者，应考虑使用羟氯喹治疗。
