STAT1基因功能获得性突变致慢性皮肤黏膜念珠菌病继发噬血细胞性淋巴组织细胞增多症1例

Hemophagocytic lymphohistiocytosis secondary to chronic mucocutaneous candidiasis caused by gain-of-function STAT1 mutations:a case report

慢性皮肤黏膜念珠菌病的疾病特征为指甲、皮肤、口腔和生殖道黏膜的反复或持续白色念珠菌感染,本病临床较少见。本病例患儿主要表现为反复口腔念珠菌病、低体重、生长迟缓,入院查体提示肝、脾、淋巴结肿大,化验提示血三系偏低、低纤维蛋白原血症、高甘油三酯血症、高铁蛋白、NK细胞活性低,骨髓涂片提示噬血性细胞可见,静脉血宏基因组二代测序、血培养、骨髓培养均提示白色念珠菌感染。患儿全外显子测序发现STAT1基因杂合错义变异c.1154C>T(p.Thr385Met),为自发变异。诊断为STAT1基因功能获得性突变致慢性皮肤黏膜念珠菌病继发噬血细胞性淋巴组织细胞增多症。先后予卡泊芬净、氟康唑抗感染治疗,住院治疗5周后出院,随访1年余未见复发及后遗症。

Chronic mucocutaneous candidiasis disease is characterized by repeated or persistent candida albicans infection of the nail,skin,oral cavity and genital tract mucosa.This disease is rare in clinical practice.The patient in this case mainly presented with recurrent oral candidiasis,low body weight,and growth retardation.The examination on admission showed enlarged liver,spleen,and lymph nodes,and the laboratory tests showed low blood tertiary,hypofibrinogenemia,hypertriglyceridemia,high ferritin,low activity of NK cells,and the bone marrow smear showed hemophagocytic cells,and the peripheral blood metagenomic next generation sequencing,blood culture and bone marrow culture all suggested Candida albicans infection.Whole exon sequencing of the child revealed a heterozygous missense variation c.1154C>T(p.Thr385Met) in the STAT1 gene,which was a spontaneous variation.The diagnosis was acquired mutation in the STAT1 gene causing chronic mucocutaneous candidiasis disease secondary to hemophagocytic lymphohistiocytosis.The patient received anti-infection treatment with caspofungin and fluconazole successively,and was discharged from hospital after 5 weeks of hospitalization.No recurrence or sequelae were observed over 1 year after discharge.