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JEADV:芳香酶抑制剂治疗乳腺癌患者额部纤维性脱发2例

2022-03-12 医路坦克 MedSci原创

脱发是已知的芳香化酶抑制剂的潜在副作用,本文报告了两例服用阿那曲唑辅助治疗的绝经后激素受体(雌激素和孕酮)阳性的乳腺癌患者发展为额叶纤维性脱发的病例。

    脱发是已知的芳香化酶抑制剂的潜在副作用,但调查其患病率和结局的研究有限。在接受阿那曲唑治疗的乳腺癌幸存者中,还没有关于瘢痕性脱发的描述。我们报告两例服用阿那曲唑辅助治疗的绝经后激素受体(雌激素和孕酮)阳性的乳腺癌患者,她们发展为额叶纤维性脱发。

     一名70岁出头的女性出现进行性脱发6个月,她绝经后20年,在出现前18个月开始服用阿那曲唑(图1)。第二位患者年近七十,逐渐脱发,发际线衰退达三个月之久。她绝经27年后,在她出现之前已经开始服用阿那曲唑4个月(图2)。这两名患者都是激素受体阳性的乳腺癌,接受了肿块切除和放射治疗。他们没有接受化疗,病情仍在缓解中。两例患者头皮检查均显示额部和颞部发际线中度至重度变薄,经毛管镜检查证实,毛囊开口呈片状消失,毛囊周围有红斑,毛发沿发际线有管状铸型。女性模式的头发稀疏,眉毛脱落也很明显。两种头皮活检的组织病理学均显示纤维束和纤维化,小叶周围有中等程度的地衣样淋巴细胞浸润。两名患者的临床和组织病理学结果均与额叶纤维性脱发相一致。患者1服用羟氯喹200 mg,每日2次,连续1年,随后逐渐减少至每日1次。视网膜筛查和重新评估是正常的。例2服用多西环素100 mg,每日1次,未见不良反应。两名患者均每日外用5%米诺地尔和0.1%他克莫司软膏治疗,治疗3年后病情稳定。在此期间,两名患者的阿那曲唑治疗均未中断。

图1 激素受体阳性乳腺癌阿那曲唑治疗18个月后绝经后妇女的前发际衰退。

图2 激素受体阳性乳腺癌患者服用阿那曲唑四个月后的前额发际线后退。

    FFA的特征是毛囊突起的免疫豁免性崩溃,上皮毛囊干细胞遭到破坏。我们的患者在服用阿那曲唑后额部和颞部头皮脱发的快速进展表明,疾病过程可能是由这种药物引发的。细胞色素P-450芳香化酶是一种微粒体酶,能将睾酮和4-雄烯二酮分别转化为雌二醇和雌酮。它是一种重要的酶,通过将雄激素转化为雌激素来限制毛囊中雄激素的含量。它还影响5a还原底物的形成,这些底物与雄激素受体具有很高的亲和力,从而启动雄激素细胞事件。

    因此,芳香化酶抑制剂治疗的患者可能会出现雄激素性脱发作为不良反应之一。5α-还原酶抑制剂(5ARI)最近被列为FFA治疗的一部分,回顾研究表明,5ARI特别是一起接受度他雄胺治疗的FFA患者的病情已趋于稳定。

   我们曾假设雄激素敏感区的小型化毛发是FFA的靶点,因此5ARI协同最大限度地减少了毛囊靶点的进一步破坏和瘢痕性脱发的发展。然而,激素因素在其发病机制中的确切机制和影响尚不清楚。芳香酶抑制剂导致的雄激素性脱发的加速进展可能是导致这些易感患者的FFA炎症过程的原因。

    这些患者的FFA可能是在这些患者中偶然发生的,然而,在这个队列中进行更大规模的研究是有必要的,以更好地了解瘢痕性脱发的发病机制。这使得在开始治疗前对病人进行更有效的咨询。最后,应该进一步研究乳腺癌幸存者的FFA治疗方案和结果。

文献来源: Murad A,  Wolinska A,  Bergfeld WF,Frontal fibrosing alopecia in breast cancer patients on aromatase-inhibitor: 2 cases.J Eur Acad Dermatol Venereol 2022 Jan 23.

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    2022-11-09 仁医06
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    2022-06-06 jklm09
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