Jantzem H, Dupre-Goetghebeur D, Spindler P, Merrer J
Centre régional de pharmacovigilance de Brest, CHU La-Cavale-Blanche, boulevard Tanguy-Prigent, 29609 Brest cedex, France.
Ann Dermatol Venereol. 2009 Dec;136(12):894-7. doi: 10.1016/j.annder.2009.09.010.
Sorafenib has been approved for use in the treatment of metastatic renal cell carcinoma. Cutaneous side-effects are common, including rash, hand-foot syndrome, alopecia, pruritus, dry skin and erythema. We report an original unexpected cutaneous effect: multiple keratoacanthomas. In the light of a literature review of drug-induced keratoacanthomas, we discuss the potential underlying physiopathological mechanism.
Three weeks after starting treatment with sorafenib for metastatic renal cell carcinoma, a 64-year-old man developed skin lesions on the face, ears, forearms and thighs having the appearance of dome-shaped nodules with central keratotic cores. Eruptive keratoacanthomas were suspected and were in fact confirmed by histology. Thanks to effective antiangiogenic treatment and the mild discomfort of the keratoacanthomas, sorafenib could be continued. Three weeks after the end of treatment, all lesions had regressed and the patient's skin returned to normal.
Although the precise aetiology is unknown, the development of eruptive keratoacanthomas is associated with impaired immunity, sun exposure, viral infection, genetic predisposition, radiation therapy and exposure to chemical carcinogens. A few cases of drug-induced keratoacanthomas have been described in the literature and certain immunosuppressant drugs have been implicated. This case suggests that the novel antineoplastic agent sorafenib has a complex activity that, in addition to tyrosine kinases inhibition, includes an immunosuppressant mechanism that can occasionally cause skin lesions.
索拉非尼已被批准用于治疗转移性肾细胞癌。皮肤副作用很常见,包括皮疹、手足综合征、脱发、瘙痒、皮肤干燥和红斑。我们报告了一种原本未预料到的皮肤效应:多发性角化棘皮瘤。鉴于对药物性角化棘皮瘤的文献综述,我们讨论了潜在的生理病理机制。
一名64岁男性在开始使用索拉非尼治疗转移性肾细胞癌三周后,面部、耳部、前臂和大腿出现皮肤病变,表现为带有中央角质核心的圆顶形结节。怀疑为爆发性角化棘皮瘤,组织学检查证实了这一诊断。由于有效的抗血管生成治疗以及角化棘皮瘤引起的不适较轻,索拉非尼得以继续使用。治疗结束三周后,所有病变均消退,患者皮肤恢复正常。
尽管确切病因尚不清楚,但爆发性角化棘皮瘤的发生与免疫功能受损、阳光照射、病毒感染、遗传易感性、放射治疗以及接触化学致癌物有关。文献中已描述了一些药物性角化棘皮瘤病例,某些免疫抑制药物与之有关。该病例表明,新型抗肿瘤药物索拉非尼具有复杂的活性,除了抑制酪氨酸激酶外,还包括一种免疫抑制机制,偶尔会导致皮肤病变。