Exemestane‐induced radiation recall dermatitis and morbilliform rash
Exemestane‐induced radiation recall dermatitis and morbilliform rash
复制标题
依西美坦诱发的放射回忆性皮炎和麻疹样皮疹
DOI：
10.1111/1346-8138.13238
复制
发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Y. Le Corre
中科院分区：
文献类型：
--
作者：
A. Marchand;M. Georgin;P. Cellier;Ludovic Martin;M. Avenel‐Audran;Y. Le Corre
放射性回忆性皮炎（RRD）是一种罕见的现象，定义为放射治疗或紫外线照射后全身性药物给药引发的先前照射区域内的急性炎症性皮肤反应。我们报告第一例放射性回忆性皮炎（RRD）引起的西司坦。一位74岁的女性被诊断为右乳腺II级浸润性导管癌。她接受了肿瘤切除术和腋窝前哨淋巴结活检，结果为阴性，然后在她的右乳房接受了66戈伊。辐射诱发I级放射性皮炎。阿那曲唑是一种芳香化酶抑制剂，在放射治疗后被用于对乳腺癌敏感的乳腺癌的辅助治疗。由于严重的多关节痛，阿那曲唑停药，另一种芳香酶抑制剂阿司美坦在症状完全缓解后被替代。三周后，她的右乳房出现肿胀和水肿斑块，严格限制在先前照射的皮肤上（图1）。第二天，躯干和上肢出现弥漫性斑丘疹。1400/mm时存在嗜酸性粒细胞增多。对丘疹进行皮肤活检，发现表皮海绵状增生，真皮浅层单核细胞和嗜酸性粒细胞穿过，与药物反应一致。在停用维司坦后几天，嗜酸性粒细胞增多和皮疹消退，未使用任何药物。患者拒绝皮肤试验，但临床表现符合RRD和药疹。放射性回忆性皮炎是一种急性皮肤炎症反应，发生在先前照射的区域。放射治疗和插补药物给药之间的时间间隔从一周到几年不等。传统上，患者在放射治疗期间对辐射的反应较低。剂量调整和分次给药似乎不影响发生率。皮肤是辐射回忆毒性的主要部位，但据报道也涉及其他器官。它可以从轻微的皮疹到溃疡或皮肤坏死。当不严重时，它往往会在停药后迅速自发消退，但仍需密切观察。可以使用局部皮质类固醇，很少需要全身皮质类固醇。降低剂量可进行再激发，且不一定会诱导反应。放射性回忆性皮炎已报告与几种药物，包括抗癌药，他莫昔芬和维罗非尼，但从来没有与阿司美坦。值得注意的是，RRD从未被观察到与一些常用的化疗药物，如环磷酰胺，这表明这种现象是非常药物特异性。我们的观察是基于RRD和药疹在同一患者中的关联。其机制可能基于特异质药物超敏反应，可能伴随累积DNA损伤和氧化应激后炎症途径的非免疫激活。辐射可能会在辐射区域的存活细胞内引起遗传性突变，特别是在由于“记忆”反应而无法耐受后续化疗的干细胞中。局部血管通透性也可能影响某些药物的后续药代动力学，从而引发RRD。嗜酸性粒细胞增多症的发生从未被描述在这种现象。这里，它可能与斑丘疹有关。
Dear Editor, Radiation recall dermatitis (RRD) is an uncommon phenomenon defined by an acute inflammatory skin reaction within a previously irradiated area, triggered by the administration of systemic agents after radiotherapy or ultraviolet light. We report the first case of radiation recall dermatitis (RRD) induced by exemestane. A 74-year-old woman was diagnosed with grade II infiltrating ductal carcinoma of the right breast. She underwent tumorectomy with axillary sentinel lymph node biopsy, which was negative, and then received 66 Gy on her right breast. Irradiation induced grade I radiodermatitis. Anastrozole, an aromatase inhibitor indicated as adjuvant therapy in hormone-sensitive breast cancers, was instigated following radiation therapy. Because of severe polyarthralgia, anastrozole was withdrawn and exemestane, another aromatase inhibitor, was substituted after complete resolution of her symptoms. Three weeks later, she developed an erythematous and edematous plaque on her right breast, strictly limited to the previously irradiated skin (Fig. 1). The next day, a diffuse maculopapular eruption appeared on the trunk and upper extremities. Hypereosinophilia at 1400/mm was present. A skin biopsy of a papule was performed and demonstrated epidermal spongiosis, traversed by mononuclear cells and eosinophils in the superficial dermis compatible with a drug reaction. Hypereosinophilia and rash regressed a few days after withdrawal of exemestane without any medication. The patient refused skin tests, but the clinical presentation is compatible with RRD and drug eruption. Radiation recall dermatitis is an acute skin inflammatory reaction occurring on previously irradiated areas. The time interval between radiotherapy and administration of the imputed drug varies from a week to years. Classically, patients have a low reaction to radiation during radiotherapy. Modification of the dose and fractionation do not seem to influence the incidence. The skin is the major site of radiation recall toxicity but other organs have also been reported to be involved. It can range from mild rash to ulceration or skin necrosis. When not severe, it tends to resolve spontaneously and rapidly after withdrawal of the causal agent but close observation remains essential. Topical corticosteroids can be used and systemic corticosteroids are rarely necessary. Rechallenge is possible with reduced doses and does not always induce a reaction. Radiation recall dermatitis has been reported with several drugs, including anticancer agents, tamoxifen and vemurafenib, but never with exemestane. Remarkably, RRD has never been observed with a number of usual chemotherapy drugs, such as cyclophosphamide, suggesting that the phenomenon is very drug-specific. The originality of our observation is based on the association of both RRD and drug eruption in the same patient. The mechanism is probably based on idiosyncratic drug hypersensitivity reactions, probably with non-immune activation of inflammatory pathways, following cumulative DNA damage and oxidative stress. Radiation may cause heritable mutations within survival cells in the irradiated area, especially in the stem cells that are unable to tolerate subsequent chemotherapy because of a “remembered” reaction. Local vascular permeability may also affect the subsequent pharmacokinetics of certain drugs to provoke RRD. The occurrence of hypereosinophilia has never been described in this phenomenon. Here, it is probably related to the maculopapular rash.