Department of Dermatology, Hôpital Cochin, APHP, University René Descartes, Paris, France.
Br J Dermatol. 2013 Oct;169(4):934-8. doi: 10.1111/bjd.12555.
Vemurafenib, a selective BRAF (v-raf murine sarcoma viral oncogene homologue B1) kinase inhibitor, is a new targeted biotherapy that improves survival in patients with metastatic melanomas harbouring the BRAF V600E mutation. However, this drug has significant dermatological adverse effects. We report a new severe cutaneous reaction to this drug associated with acute kidney injury (AKI). Four patients presented a generalized grade 3 (Common Terminology Criteria for Adverse Events) erythematous eruption with hyperkeratosis pilaris, 5-14 days after the introduction of vemurafenib. These symptoms were associated with AKI in all cases and transitory hypereosinophilia in two cases. Vemurafenib treatment was stopped in three patients and the dose was reduced in the fourth, leading to a gradual improvement of skin symptoms and renal function. Positron-emission tomography scans showed a complete response in three cases and a major response in one case. Vemurafenib was reintroduced at a lower dose, without a relapse of the rash, but renal function again deteriorated. Thus, we report a cluster of four cases of AKI associated with similar, severe, grade 3 cutaneous drug reactions related to vemurafenib.
维莫非尼，一种选择性 BRAF（鼠肉瘤病毒致癌基因同源物 B1）激酶抑制剂，是一种新的靶向生物疗法，可改善携带 BRAF V600E 突变的转移性黑色素瘤患者的生存。然而，这种药物有显著的皮肤不良事件。我们报告了一种与急性肾损伤（AKI）相关的新的严重皮肤反应。四名患者在接受维莫非尼治疗 5-14 天后出现全身性 3 级（不良事件通用术语标准）红斑性皮疹，伴有毳毛角化过度。这些症状在所有情况下均与 AKI 相关，在两种情况下与短暂性嗜酸性粒细胞增多相关。三名患者停止了维莫非尼治疗，第四名患者减少了剂量，导致皮肤症状和肾功能逐渐改善。正电子发射断层扫描显示，三名患者完全缓解，一名患者主要缓解。维莫非尼以较低剂量重新引入，皮疹无复发，但肾功能再次恶化。因此，我们报告了四例 AKI 相关的类似严重 3 级皮肤药物反应的病例，这些反应均与维莫非尼有关。
