University of Illinois College of Medicine, Chicago.
Department of Dermatology, Harvard Medical School, Boston, Massachusetts.
JAMA Dermatol. 2014 Mar;150(3):307-11. doi: 10.1001/jamadermatol.2013.7919.
Targeted BRAF inhibitor therapy (vemurafenib, dabrafenib) is an effective, novel treatment for patients with metastatic melanoma with the V600E BRAF mutation. This therapy is associated with squamous cell carcinomas and keratoacanthomas. Granulomatous eruptions have not been previously reported.
Two patients with melanoma developed cutaneous granulomatous eruptions during targeted BRAF inhibitor therapy. In case 1, after 2 months of treatment with dabrafenib and trametinib (MEK inhibitor), a papular eruption concerning for progression of disease prompted cessation of treatment. After the histopathologic diagnosis of granulomas, the patient was treated with clobetasol ointment with resolution within days and resumption of therapy. In case 2, after 5 months of vemurafenib treatment, the patient developed a granulomatous eruption, which resolved 3 weeks after cessation of therapy.
We report 2 cases of cutaneous granulomatous eruptions on treatment with targeted BRAF inhibitors, a previously unreported association. Although additional investigations are necessary to better elucidate the pathogenic mechanisms, our report includes a treatment plan that prevents unnecessary discontinuation of therapy. Given the Food and Drug Administration approval of vemurafenib for metastatic melanoma, clinicians should be aware of this possible cutaneous reaction and treatment option to optimize patient management.
针对 BRAF 抑制剂(vemurafenib、dabrafenib)的靶向治疗是一种有效的新型治疗方法,适用于 V600E BRAF 突变的转移性黑色素瘤患者。这种治疗方法与鳞状细胞癌和角化棘皮瘤有关。以前未报告过肉芽肿性皮疹。
两名接受靶向 BRAF 抑制剂治疗的黑色素瘤患者出现了皮肤肉芽肿性皮疹。在病例 1 中,在用 dabrafenib 和 trametinib(MEK 抑制剂)治疗 2 个月后,出现了丘疹性皮疹,提示疾病进展,因此停止了治疗。在组织病理学诊断为肉芽肿后,患者接受了卤米松软膏治疗,数天内皮疹消退,并恢复了治疗。在病例 2 中,在接受 vemurafenib 治疗 5 个月后,患者出现了肉芽肿性皮疹,停药 3 周后皮疹消退。
我们报告了 2 例接受靶向 BRAF 抑制剂治疗的皮肤肉芽肿性皮疹,这是以前未报道过的关联。尽管需要进一步研究以更好地阐明发病机制,但我们的报告包括了一种治疗方案,可以防止不必要地停止治疗。鉴于食品和药物管理局批准 vemurafenib 用于转移性黑色素瘤,临床医生应该意识到这种可能的皮肤反应和治疗选择,以优化患者管理。