粒细胞集落刺激因子治疗先天性免疫缺陷继发深部真菌感染二例并文献复习

Application of granulocyte colony stimulating factor in the treatment of invasive fungal infections in congenital immunodeficiency： Two pediatric cases reports and review of literatures

目的讨论粒细胞集落刺激因子（G-CSF）在免疫缺陷合并白细胞介素-17降低后继发深部白色念珠菌感染中的治疗意义。方法回顾性研究2例经基因检查确诊的免疫缺陷患儿，继发深部白色念珠菌感染后的诊疗经过，并结合相关文献进行讨论。结果2例患儿分别为CARD9和STAT1缺陷，分别患有白色念珠菌性脑膜炎和肺脓肿，血白细胞介素-17水平下降，正规抗真菌药物治疗效果不佳，经过G-CSF辅助治疗后，2例患儿的症状/体征及影像学异常均恢复，并经过5～10个月随访，感染未再反复。结论抗真菌药物联合G-CSF治疗，可以有效地提高部分免疫缺陷合并深部真菌感染患儿的治疗效果。对于不明原因条件致病菌引发深部真菌感染的患儿，应介入基因检测寻找可能存在的免疫缺陷，利于制定更个体化的治疗方案。

ObjectiveTo discuss the therapeutic significance of granulocyte colony stimulating factor （G-CSF） in the treatment of invasive Candida infections in congenital immunodeficiency, especially in cases with low level of interleukin 17（IL-17）.MethodsTherapeutic processes of 2 children suffering from invasive Candida infections secondary to congenital immunodeficiency were retrospectively studied, furthermore, the related literatures were also reviewed.ResultsWhole-exome sequencing revealed CARD9 mutation in the first patient, who suffered from Candida albicans meningoencephalitis, while the other patient revealed STAT1 mutation suffering from recurrent lung abscess caused by Candida albicans, and both of them showed low level of blood IL-17.Routine antifungal drugs were insufficiency, even treatment period had prolonged for several months.But after the G-CSF adjuvant therapy, their symptoms, signs and images recovered.With 5 to 10 months follow-up, no recurrent infections were found.ConclusionAntifungal drugs combined with G-CSF can effectively improve the treatment effect in invasive fungal infections secondary to immunodeficiency.Further more, genetic screening especially whole-exome sequencing can be suggested to find unusual immunodeficiency, which helps more individualized treatment.