<i>STAT1</i>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

阮培森; 郑耀; 陈赫赫

doi:10.16766/j.cnki.issn.1674-4152.003443

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

doi: 10.16766/j.cnki.issn.1674-4152.003443

1.
宁波市妇女儿童医院重症医学科, 浙江宁波 315000
2.
宁波市妇女儿童医院血液科

基金项目:

浙江省医药卫生科技计划项目 2023RC085

宁波市科技计划项目 2019A21002

宁波市医学重点学科建设计划项目 2022-B17

宁波市第一批医疗卫生高端团队重大攻坚项目 2022020405

宁波市卫生健康科技计划项目 2022Y17

详细信息

作者简介:
陈赫赫，E-mail：pt1223@126.com

中图分类号: R756.5 R557.4
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- 被引次数: 0
出版历程
- 收稿日期: 2023-07-27
- 网络出版日期: 2024-05-27

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

1.
Department of Critical Care Medicine, Ningbo Women and Children' s Hospital, Ningbo, Zhejiang 315000, China

摘要

摘要: 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。
- 慢性皮肤黏膜念珠菌病 /
- STAT1基因 /
- 侵袭性念珠菌病 /
- 噬血细胞性淋巴组织细胞增多症
Abstract: 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.
- Chronic mucocutaneous candidiasis disease /
- Gain-of-function STAT1 mutations /
- Invasive candidiasis /
- Hemophagocytic lymphohistiocytosis

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图 1 患儿血培养菌落及涂片镜检情况

注：A示外观浅绿色、翠绿色、深绿色、隆起、表面光滑的乳酪样菌落(37 ℃，CHROMagar Candida显色培养基，培养48 h)；B示革兰染色阳性，着色不均，孢子圆形、卵圆形、长圆形，壁薄，大小不等，有的孢子出芽形成芽孢、牙管或假菌丝(油镜下，革兰染色，×1 000)。

Figure 1. Blood culture colonies and microscopic smear examination in pediatric patient

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图 2 患儿骨髓涂片

注：A示涂片可见巨噬细胞对幼红细胞吞噬，偶见吞噬真菌；B示涂片可见巨噬细胞对幼红细胞和中性粒细胞吞噬。

Figure 2. Bone marrow smear of a pediatric patient

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图 3 患儿家系基因测序图

注：在患儿的STAT1基因中存在杂合错义变体c.1154C>T(p.Thr385Met)，父亲及母亲未见该变异。箭头表示先证者；圆圈表示女性；方块表示男性。箭头指示填充的符号表示受影响的个体。

Figure 3. Genetic sequencing diagram depicting the family lineage of a pediatric patien

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表 1 AD-STAT1-GOF致CMCD继发HLH患儿随访临床特征分析

Table 1. Analysis of clinical characteristics during follow-up in children with secondary HLH resulting from STAT1-GOF associated with CMCD

项目	随访次数
项目	1	2	3	4	5	6	7	8
离出院日(d)	7	28	64	118	188	272	354	452
临床症状(发热、肝脾大、CMCD症状等)	×	×	×	×	×	×	×	×
实验室检查
白细胞计数(×10⁹/L)	5.3	5.1	6.9	8.6	8.0	9.7	6.3	5.8
血红蛋白(g/L)	126	133	135	118	123	135	121	124
血小板计数(×10⁹/L)	279	251	266	148	295	359	226	247
超敏C反应蛋白(mg/L)	0.6	0.5	0	0	0	0.1	0	0.7
丙氨酸氨基转移酶(U/L)	46	17	21	16	13	35	10	24
血肌酐(μmol/L)	28	15	17	22	10	31	17	8
甘油三酯(mmol/L)	0.47	0.32	0.54	0.34	0.31	0.27	0.51	0.36
活化部分凝血活酶时间(s)	38.3	27.6	30.5	40.6	28.2	36.3	34.1	31.2
纤维蛋白原(mg/dL)	192	233	256	247	289	250	235	255
铁蛋白(ng/mL)	103	63	42	45	35	40	58	32
真菌(1, 3)-β-d-glucan(pg/mL)	＜37.5	＜37.5	＜37.5	＜37.5	＜37.5	＜37.5	＜37.5	＜37.5
血培养	×	×	O	×	O	×	×	×
注：AD-STAT1-GOF，常染色体显性遗传STAT1基因功能获得性变异；CMCD，慢性皮肤黏膜念珠菌病；HLH，噬血细胞性淋巴组织细胞增多症；“×”为阴性; “O”为未检测。

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