Department of Emergency Medicine, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
Am J Ther. 2011 Nov;18(6):e274-6. doi: 10.1097/MJT.0b013e3181debc6f.
Tacrolimus is a potent immunosuppressant medication with a low therapeutic index. We report a case of mutism with persistent dysarthria in a patient receiving tacrolimus-based immunosuppression following allogeneic liver transplantation. A 59-year-old female patient with end-stage liver disease secondary to primary sclerosing cholangitis underwent successful allogeneic liver transplantation. The patient was started on tacrolimus for prevention of allograft rejection and subsequently developed complete mutism. Following consultation of the medical toxicology service, tacrolimus was discontinued and the patient's mutism gradually improved. However, the patient still has moderate dysarthria more than 2 years after tacrolimus discontinuation. The Naranjo probability scale revealed a probable adverse reaction of mutism and dysarthria associated with tacrolimus therapy. Mutism is an uncommon complication of calcineurin inhibitors. Both cyclosporine and tacrolimus have been associated with mutism, though mutism may be more common in patients treated with tacrolimus. The mechanism of injury has not been delineated, although liver transplant patients and patients with preexisting hepatic encephalopathy or neurologic disease may be at increased risk for this complication. The mainstay of treatment is tacrolimus dose reduction or discontinuation, although benzodiazepine therapy may be beneficial in the treatment of this disorder. Clinicians should be aware of the potential adverse effects associated with calcineurin inhibitor toxicity in transplant patients and should advocate for aggressive and rapid treatment of this serious adverse drug effect.
他克莫司是一种具有低治疗指数的强效免疫抑制剂。我们报告了一例在接受同种异体肝移植后接受他克莫司免疫抑制治疗的患者出现缄默症伴持续性构音障碍的病例。一名 59 岁女性患者，因原发性硬化性胆管炎导致终末期肝病，成功接受了同种异体肝移植。该患者开始使用他克莫司预防移植物排斥反应，随后出现完全缄默。在咨询医学毒理学服务后，停用了他克莫司，患者的缄默症逐渐改善。然而，停用他克莫司超过 2 年后，患者仍存在中度构音障碍。Naranjo 概率量表显示，缄默症和构音障碍与他克莫司治疗相关的可能性不良反应。缄默症是钙调神经磷酸酶抑制剂的一种罕见并发症。环孢素和他克莫司都与缄默症有关，但缄默症在接受他克莫司治疗的患者中可能更为常见。损伤机制尚未阐明，尽管肝移植患者和有既往肝性脑病或神经疾病的患者可能更容易发生这种并发症。治疗的主要方法是减少他克莫司剂量或停用他克莫司，尽管苯二氮䓬类药物治疗可能对治疗这种疾病有益。临床医生应了解与移植患者中钙调神经磷酸酶抑制剂毒性相关的潜在不良反应，并应倡导积极快速治疗这种严重的药物不良反应。
