Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland.
Br J Dermatol. 2012 Feb;166(2):422-4. doi: 10.1111/j.1365-2133.2011.10591.x. Epub 2011 Dec 5.
Recent studies suggest that patients on mammalian target of rapamycin (mTOR) inhibitors experience a reduction in cutaneous carcinogenesis by an estimated 50% or more compared with calcineurin inhibitors. While randomized trials are running, organ transplant recipients are frequently switched from calcineurin inhibitors to mTOR inhibitors when cutaneous carcinogenesis increases.
To slow carcinogenesis in our patient, a heart transplant recipient with a neuropathic diabetic foot syndrome who had developed cutaneous carcinogenesis at a rate of more than 20 squamous cell carcinomas (SCC) annually.
The patient's immunosuppression was switched from the calcineurin inhibitor ciclosporin to the mTOR inhibitor everolimus.
Carcinogenesis slowed to six SCC annually; however, he developed recalcitrant diabetic foot ulcers which were purely neuropathic and nonangiopathic, and a limb-threatening fistulating necrotic erysipelas of the right leg. Both sites responded poorly to antibiotic therapy, offloading and debridement. This skin fistula became chronic and some toes were at risk for minor amputation. In view of the propensity for mTOR inhibitors to impair would healing, immunosuppression was switched back to ciclosporin. All wounds healed rapidly, but skin carcinogenesis rose to former levels.
This case impressively illustrates the clinical dilemma for mTOR inhibitor use where benefit in carcinogenesis is counterbalanced by impairment in wound healing. Changes in immunosuppressive regimens should thus be made on an individual basis with careful consideration of the relative risks.
最近的研究表明，与钙调磷酸酶抑制剂相比，接受哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂治疗的患者皮肤癌变减少约 50%或更多。虽然正在进行随机试验，但当皮肤癌变增加时，器官移植受者经常从钙调磷酸酶抑制剂转换为 mTOR 抑制剂。
为了减缓我们的患者——一位患有神经性糖尿病足综合征的心脏移植受者的癌变速度，该患者的皮肤癌变速度每年超过 20 个鳞状细胞癌（SCC）。
将患者的免疫抑制剂从钙调磷酸酶抑制剂环孢素转换为 mTOR 抑制剂依维莫司。
癌变速度减缓至每年 6 个 SCC；然而，他出现了难治性糖尿病足溃疡，这些溃疡纯粹是神经性的，非血管性的，还有一条腿部威胁性的瘘管性坏死性丹毒。这两个部位对抗生素治疗、减压和清创的反应都很差。这个皮肤瘘管变成了慢性的，有些脚趾有轻微截肢的风险。鉴于 mTOR 抑制剂会损害伤口愈合的倾向，将免疫抑制转换回环孢素。所有的伤口都迅速愈合，但皮肤癌变又回到了以前的水平。
这个病例令人印象深刻地说明了 mTOR 抑制剂使用的临床困境，即癌变获益与伤口愈合受损相平衡。因此，应根据个体情况，仔细考虑相对风险，改变免疫抑制方案。
