基于文献病例的他克莫司致急性胰腺炎临床特征分析

Analysis of clinical features of tacrolimus induced acute pancreatitis based on literature cases

目的探讨他克莫司相关急性胰腺炎(AP)的临床特征。方法检索CNKI、WanFang Data、VIP、PubMed和Web of Science等中英文文献数据库(截至2023年3月10日),收集他克莫司相关AP的病例报告文献,提取相关数据并进行描述性统计分析。结果共收集17篇文献共19例病例,其中男性10例,女性9例;年龄3~65岁。共发生他克莫司相关AP 21例次。11例次AP发作时他克莫司血药浓度水平>15 ng·mL^(-1),其中8例次接近或超过30 ng·mL^(-1)。19例次患者首次应用他克莫司后诱导AP时间为3 d~7年,中位时间为20 d,2例再诱发AP时间分别为37 d和75 d。他克莫司相关AP的临床症状、实验室、影像学检查结果与其他药物引起的AP类似,主要症状为腹痛,部分患者伴有恶心、呕吐、腹泻,少部分患者合并糖尿病或糖尿病酮症症状,严重者合并休克。诊断AP后,20例次有停药或对症支持治疗的描述,15例次患者及时停用或降低他克莫司剂量。15例次症状缓解或好转,5例死亡,其中与AP相关的死亡2例。结论他克莫司可能会引起AP,一般预后较好,严重者可出现死亡。早期识别并及时处理至关重要,特别是对于合并使用多种药物患者应密切监测他克莫司血药浓度。

Objective To explore the clinical features of tacrolimus-related acute pancreatitis(AP).Methods The databases of CNKI,Wanfang Data,VIP,PubMed and Web of Science were searched(up to March 10,2023),and the case reports of tacrolimus-related AP were collected and descriptively analyzed.Results A total of 19 cases were collected from 17 documents,including 10 males and 9 females,ages ranged from 3 to 65 years.A total of 21 casetimes of tacrolimus related AP occurred.The plasma concentration of tacrolimus was more than 15 ng·mL^(-1)in 11 case-times of AP,of which 8 case-times were close to or more than 30 ng·mL^(-1).The time from the first application of tacrolimus to the occurrence of AP in 19 patients was 3 days to 7 years,the median time was 20 days,and the second occurrence of AP in 2 patients was 37 days and 75 days,respectively.The clinical symptoms,laboratory tests,and imaging findings of tacrolimus-related AP were similar to those caused by other drugs.The main symptom was abdominal pain,some patients were accompanied by nausea,vomiting and diarrhea,a small number of patients with diabetes or diabetes ketosis symptoms,and severe patients with shock symptoms.Aſter the diagnosis of AP,treatment measures were described in 20 cases,15 patients discontinued or reduced the dose of tacrolimus.15 case-times were relieved or improved,5 cases died,including 2 cases of AP-related death.Conclusions Tacrolimus may cause AP,with a generally good prognosis,and in severe cases,death may occur.Early identification and timely treatment are essential,especially for patients treated with multiple drugs.The blood concentration of tacrolimus should be closely monitored.