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伴有严重前房积血的葡萄膜炎患者房水中水痘带状疱疹病毒的基因分析

Genetic analysis of varicella-zoster virus in the aqueous humor in uveitis with severe hyphema.

作者信息

Hosogai Mayumi, Nakatani Yoko, Mimura Kensuke, Kishi Shoji, Akiyama Hideo

机构信息

Department of Ophthalmology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.

Department of Virology and Preventive Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.

出版信息

BMC Infect Dis. 2017 Jun 15;17(1):427. doi: 10.1186/s12879-017-2518-2.

DOI:10.1186/s12879-017-2518-2
PMID:28619012
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5472993/
Abstract

BACKGROUND

Genetic variations have been identified in the genome of varicella-zoster virus (VZV) strains using vesicle fluid, varicella scabs and throat swab samples. We report a rare case of VZV-associated uveitis with severe hyphema, which was immediately diagnosed by polymerase chain reaction (PCR) using the aqueous humor, in which we were able to analyze the VZV genotype for the first time.

CASE PRESENTATION

A 16-year-old Japanese boy was referred to our hospital with a 20-day history of unilateral anterior uveitis and 11-day history of hyphema. At presentation, details of the iris, the iridocorneal angle, and the fundus were not visible due to the severe hyphema. Serum anti-VZV IgG and anti-VZV IgM were elevated, and 1.61 × 10 copies/mL of VZV-DNA were detected by real-time PCR using the aqueous humor. As there were no eruptions on his face or body, we diagnosed zoster sine herpete and started intravenous administration of prednisolone and acyclovir. The hyphema completely disappeared 2 weeks after presentation, while sectorial iris atrophy and mild periphlebitis of the fundus became gradually apparent. Anterior inflammation and periphlebitis gradually improved and VZV-DNA in the aqueous humor was reduced to 1.02 × 10 copies/mL at 4 weeks after presentation. Examination by slit lamp microscope revealed no inflammation after 5 months, and VZV-DNA could no longer be detected in the aqueous humor. Serum anti-VZV IgG and anti-VZV IgM also showed a gradual decrease along with improvement in ocular inflammation. The genetic analysis of multiple open reading frames and the R5 variable repeat region in the VZV genes, using DNA extracted from the aqueous humor at presentation, showed that the isolate was a wild-type clade 2 VZV strain (prevalent in Japan and surrounding countries) with R5A allele and one SNP unique to clade 1 (both are major types in Europe and North America).

CONCLUSIONS

VZV-associated uveitis may develop hyphema that obscures ocular inflammation, thus PCR analysis using the aqueous humor is the key investigation necessary for the diagnosis. The measurement of VZV-DNA copies by real-time PCR would be useful for evaluation of therapeutic effects. We could amplify and analyze VZV genotype using the aqueous humor including a very large number of VZV-DNA copies (1.61 × 10 copies/mL).

摘要

背景

已利用水疱液、水痘痂皮和咽拭子样本在水痘-带状疱疹病毒(VZV)毒株的基因组中鉴定出基因变异。我们报告了一例罕见的伴有严重前房积血的VZV相关性葡萄膜炎病例,通过使用房水进行聚合酶链反应(PCR)立即确诊,在此过程中我们首次能够分析VZV基因型。

病例介绍

一名16岁日本男孩因单侧前葡萄膜炎20天病史和前房积血11天病史转诊至我院。就诊时,由于严重的前房积血,虹膜、虹膜角膜角和眼底的细节均不可见。血清抗VZV IgG和抗VZV IgM升高,使用房水通过实时PCR检测到1.61×10拷贝/mL的VZV-DNA。由于其面部和身体无皮疹,我们诊断为无疱疹性带状疱疹,并开始静脉注射泼尼松龙和阿昔洛韦。就诊2周后前房积血完全消失,而扇形虹膜萎缩和眼底轻度静脉周围炎逐渐明显。前葡萄膜炎和静脉周围炎逐渐改善,就诊4周时房水中的VZV-DNA降至1.02×10拷贝/mL。裂隙灯显微镜检查显示5个月后无炎症,房水中不再能检测到VZV-DNA。血清抗VZV IgG和抗VZV IgM也随着眼部炎症的改善而逐渐下降。使用就诊时从房水中提取的DNA对VZV基因中的多个开放阅读框和R5可变重复区域进行基因分析,结果显示分离株为野生型2型VZV毒株(在日本及周边国家流行),具有R5A等位基因和1型特有的一个单核苷酸多态性(两者均为欧洲和北美的主要类型)。

结论

VZV相关性葡萄膜炎可能会出现掩盖眼部炎症的前房积血,因此使用房水进行PCR分析是诊断所需的关键检查。通过实时PCR测量VZV-DNA拷贝数将有助于评估治疗效果。我们能够使用含有大量VZV-DNA拷贝(1.61×10拷贝/mL)的房水扩增并分析VZV基因型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f18/5472993/c5ca3ac7b7bc/12879_2017_2518_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f18/5472993/59ca5faf23ba/12879_2017_2518_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f18/5472993/59ca5faf23ba/12879_2017_2518_Fig1_HTML.jpg
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