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在溃疡性结肠炎治疗过程中使用托法替尼出现类血管炎带状疱疹:通过 RNA 原位杂交评估局部病毒分布。

Vasculitis-like herpes zoster in the course of treatment with tofacitinib in ulcerative colitis: An assessment of local viral distribution by RNA in situ hybridization.

机构信息

Department of Dermatology, Kanazawa Medical University, Uchinada, Japan.

Department of Dermatology, Aichi Medical University, Nagakute, Japan.

出版信息

J Dermatol. 2024 Sep;51(9):1248-1251. doi: 10.1111/1346-8138.17169. Epub 2024 Feb 27.

Abstract

A 67-year-old man had taken the janus kinase (JAK) inhibitor, tofacitinib, for ulcerative colitis. He was referred to our department for a refractory ulcer on his lower leg. We suspected vasculitis and performed skin biopsy. Histopathological examination showed multinucleated giant cells in the epidermis and fibrinoid degeneration of small vessels in the upper dermis. Varicella zoster virus (VZV) DNA was detected by polymerase chain reaction and we diagnosed the patient with atypical vasculitis-like herpes zoster. The patient was treated with oral valacyclovir, but the rash persisted and took 2 months to heal. Immunostaining using anti-VZV antibody was positive mainly in epidermal keratinocytes, but was also observed to be positive in cells in the dermis. We further performed RNA in situ hybridization using a VZV ORF9 mRNA probe and clearly showed that the distribution of VZV mRNA extended into the dermis, including the dermal vessel walls and the eccrine sweat glands as well as the epidermis. The internal administration of JAK inhibitors may induce regional widespread VZV infection including vessels and involved in the formation of prolonged vasculitis-like manifestation. RNA in situ hybridization can be a potent tool for detecting the spread of VZV infection in the skin.

摘要

一位 67 岁男性因溃疡性结肠炎接受了 Janus 激酶(JAK)抑制剂托法替布治疗。他因小腿难治性溃疡被转至我科。我们怀疑为血管炎,并进行了皮肤活检。组织病理学检查显示表皮内有多核巨细胞和真皮浅层小血管纤维蛋白样变性。聚合酶链反应检测到水痘带状疱疹病毒(VZV)DNA,我们诊断为非典型血管炎样带状疱疹。患者接受了口服伐昔洛韦治疗,但皮疹持续存在,2 个月后才愈合。使用抗 VZV 抗体的免疫染色主要在表皮角质形成细胞中呈阳性,但在真皮细胞中也观察到阳性。我们进一步使用 VZV ORF9 mRNA 探针进行 RNA 原位杂交,清楚地显示 VZV mRNA 的分布延伸到真皮,包括真皮血管壁和外分泌汗腺以及表皮。JAK 抑制剂的内用可能会导致包括血管在内的区域性广泛 VZV 感染,并参与形成持久的血管炎样表现。RNA 原位杂交可以成为检测皮肤中 VZV 感染扩散的有效工具。

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