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与BRAF抑制剂维莫非尼相关的掌腱膜挛缩:一例报告

Dupuytren's contractures associated with the BRAF inhibitor vemurafenib: a case report.

作者信息

Chan Sze Wai, Vorobiof Daniel Alberto

机构信息

Sandton Oncology Centre, 159 Rivonia Road, Morningside, Sandton, Johannesburg, Gauteng, 2199, South Africa.

出版信息

J Med Case Rep. 2015 Jul 8;9:158. doi: 10.1186/s13256-015-0634-4.

Abstract

INTRODUCTION

Two previous cases of the development of Dupuytren's contractures were reported in association with BRAF inhibitor treatment for BRAF V600E mutation-positive metastatic melanoma and metastatic papillary thyroid carcinoma. We reported on a third case with a slower onset of presentation.

CASE PRESENTATION

A 66-year-old white man was diagnosed with a BRAF V600E mutated metastatic cutaneous melanoma. He was commenced on oral vemurafenib 960 mg twice daily. A marked response was achieved for his metastatic disease. He noticed a change of his hair characteristics and a feeling of "lumps" in both palms by 6 months. By 9 months, classical Dupuytren's contracture was apparent.

CONCLUSIONS

Dupuytren's contracture is not a known side effect of BRAF inhibitor treatment. The timeline for the development of Dupuytren's contracture on BRAF inhibitor treatment is not well defined. Although the etiology of Dupuytren's contracture is unknown, an increase in tumor necrosis factor has been demonstrated to be a possible mechanism. BRAF inhibition has been shown to increase immune reaction in the tumor microenvironment and is associated with high serum tumor necrosis factor level. We propose that an increased level of tumor necrosis factor associated with BRAF inhibition may increase the risk of the development of Dupuytren's contractures.

摘要

引言

之前有两例报道称,在使用BRAF抑制剂治疗BRAF V600E突变阳性转移性黑色素瘤和转移性甲状腺乳头状癌时出现了杜普伊特伦挛缩。我们报告了第三例发病较慢的病例。

病例介绍

一名66岁的白人男性被诊断为BRAF V600E突变的转移性皮肤黑色素瘤。他开始口服维莫非尼,每日两次,每次960毫克。他的转移性疾病取得了显著疗效。6个月时,他注意到头发特征发生了变化,双手掌有“肿块”感。到9个月时,典型的杜普伊特伦挛缩明显出现。

结论

杜普伊特伦挛缩不是BRAF抑制剂治疗已知的副作用。BRAF抑制剂治疗引发杜普伊特伦挛缩的时间线尚不明确。尽管杜普伊特伦挛缩的病因尚不清楚,但已证明肿瘤坏死因子增加是一种可能的机制。BRAF抑制已被证明可增加肿瘤微环境中的免疫反应,并与高血清肿瘤坏死因子水平相关。我们提出,与BRAF抑制相关的肿瘤坏死因子水平升高可能会增加杜普伊特伦挛缩发生的风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada2/4501278/bc79ed2fdadf/13256_2015_634_Fig1_HTML.jpg

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