Mahé Emmanuel, Morelon Emmanuel, Lechaton Sophie, Sang Kim-Hanh Le Quan, Mansouri Rafik, Ducasse Marie-Françoise, Mamzer-Bruneel Marie-France, de Prost Yves, Kreis Henri, Bodemer Christine
Service de Dermatologie, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France.
Transplantation. 2005 Feb 27;79(4):476-82. doi: 10.1097/01.tp.0000151630.25127.3a.
Sirolimus is an immunosuppressive drug recently developed for organ transplantation. Its mechanism of action, independent of calcineurin, is different from that of cyclosporine and tacrolimus, two calcineurin inhibitors (CIs). Because the toxicity of CIs is partly the result of calcineurin blockade, sirolimus exhibits a different toxicity profile. In this study, we evaluated the profile, frequency, and severity of cutaneous adverse events in renal transplant recipients receiving sirolimus-based therapy.
A systematic and in-depth evaluation of skin, mucous membranes, nails, and hair was performed in 80 renal transplant recipients receiving sirolimus-based therapy. The mean duration of the graft was 6 years and of sirolimus treatment was 18 months. Mycophenolate mofetil and steroids were combined with sirolimus for 74 patients. Sirolimus was used as first immunosuppressive therapy for 36 patients, and 44 patients were switched from CIs to sirolimus.
Seventy-nine patients (99%) experienced cutaneous adverse events. Twenty patients (25%) demonstrated serious adverse events, and six patients (7%) stopped sirolimus during the 3 months after the study because of cutaneous events. The most frequent of these were pilosebaceous apparatus involvement, including acne-like eruptions (46%), scalp folliculitis (26%), and hidradenitis suppurativa (12%); edematous complaints, including chronic edemas (55%) and angioedema (15%); mucous membrane disorders, including aphthous ulceration (60%), epistaxis (60%), chronic gingivitis (20%), and chronic fissure of the lips (11%); and last, nail disorders including chronic onychopathy (74%) and periungual infections (16%).
Skin disorders are frequent in renal transplant recipients receiving sirolimus as a long-term therapy. Despite the usually mild nature of skin events, they are often the reason for stopping sirolimus.
西罗莫司是一种最近开发用于器官移植的免疫抑制药物。其作用机制独立于钙调神经磷酸酶，与两种钙调神经磷酸酶抑制剂（CIs）环孢素和他克莫司不同。由于CIs的毒性部分是钙调神经磷酸酶阻断的结果，西罗莫司表现出不同的毒性特征。在本研究中，我们评估了接受以西罗莫司为基础治疗的肾移植受者皮肤不良事件的特征、频率和严重程度。
对80名接受以西罗莫司为基础治疗的肾移植受者进行了皮肤、黏膜、指甲和头发的系统深入评估。移植的平均持续时间为6年，西罗莫司治疗的平均持续时间为18个月。74名患者将霉酚酸酯和类固醇与西罗莫司联合使用。36名患者将西罗莫司用作初始免疫抑制治疗，44名患者从CIs转换为西罗莫司。
79名患者（99%）发生了皮肤不良事件。20名患者（25%）出现严重不良事件，6名患者（7%）在研究后的3个月内因皮肤事件停用西罗莫司。其中最常见的是累及皮脂腺，包括痤疮样皮疹（46%）、头皮毛囊炎（26%）和化脓性汗腺炎（12%）；水肿性症状，包括慢性水肿（55%）和血管性水肿（15%）；黏膜疾病，包括阿弗他溃疡（60%）、鼻出血（60%）、慢性牙龈炎（20%）和慢性唇裂（11%）；最后是指甲疾病，包括慢性甲病（74%）和甲周感染（16%）。
接受西罗莫司长期治疗的肾移植受者经常出现皮肤疾病。尽管皮肤事件通常性质较轻，但它们往往是停用西罗莫司的原因。
