背景:慢性肉芽肿病(CGD)是一种罕见的遗传性原发性免疫缺陷综合征,表现为反复感染和炎症并发症。尽管抗生素和抗真菌药物的预防性治疗改善了CGD患者的预后,感染仍然是死亡的主要原因。
方法:一名3岁零8个月的男童住院,主诉唇肿伴发热半个月,颈部脓肿11天。经过彻底检查,重症肺炎,呼吸衰竭,口腔颌面部间隙感染,肛周脓肿得到证实。然而,初步综合治疗后,他的病情没有改善。随后,通过宏基因组下一代测序鉴定了诺卡氏菌和烟曲霉的重叠感染。他接受了亚胺培南治疗,利奈唑胺,和伏立康唑静脉注射,加口服复方磺胺甲恶唑。稍后,他的病情好转了。通过全外显子组测序,患儿最终被诊断为CYBB基因突变引起的X连锁慢性肉芽肿病(X-CGD).异基因造血干细胞移植是潜在的治疗方法,但没有可用于儿童的人类白细胞抗原相容供体。家属要求转到上级医院进一步治疗。两个月后,我们跟踪了孩子的家人。不幸的是,这个孩子因严重感染而过期。
结论:据我们所知,这是中国首例X-CGD患儿通过宏基因组下一代测序鉴定出的诺卡氏菌和烟曲霉重叠感染病例.对于传统检测方法难以诊断的感染性病原体,宏基因组下一代测序被推荐作为微生物鉴定的一种辅助或不可或缺的方法。X-CGD患者预后不良,早期诊断和干预X-CGD可能降低死亡率。
BACKGROUND: Chronic granulomatous disease (CGD) is a rare inherited primary immunodeficiency syndrome, manifested as recurrent infections and inflammatory complications. Although prophylactic treatment with antibiotics and antifungals improved the outcome of CGD patients, infections remain the major cause of mortality.
METHODS: A boy aged 3 years and 8 months was admitted to hospital complaining of lip swelling with fever for half a month and neck abscess for 11 days. After a thorough examination, severe pneumonia, respiratory failure, oral and maxillofacial space infection, and perianal abscess were confirmed. However, his condition didn\'t improve after initial comprehensive therapy. Subsequently, overlapping infections of Nocardia farcinica and Aspergillus fumigatus were identified by metagenomic next-generation sequencing. He was treated with imipenem, linezolid, and voriconazole intravenously, plus taking oral compound sulfamethoxazole. Later, his condition improved. Through whole-exome sequencing, the child was ultimately diagnosed as X-linked chronic granulomatous disease (X-CGD) caused by CYBB gene mutation. Allogeneic hematopoietic stem cell transplantation was the potential sanative approach but there were no available human leukocyte antigen compatible donors for the child. The family requested to transfer to a superior hospital for further treatment. Two months later, we followed up the child\'s family. Unfortunately, the child had expired due to severe infection.
CONCLUSIONS: To our knowledge, this is the first case of overlapping infection of Nocardia farcinica and Aspergillus fumigatus identified by metagenomic next-generation sequencing in a child with X-CGD from
China. For infectious pathogens that are hard to diagnosis by traditional detection methods, metagenomic next-generation sequencing is recommended as an adminicle or indispensable approach for microbial identification. Patients with X-CGD have poor prognosis, early diagnosis and intervention of X-CGD may reduce the mortality.