BACKGROUND The development of immune checkpoint inhibitors(ICIs)has heralded a new era in cancer treatment,enabling the possibility of long-term survival in patients with metastatic disease.Unfortunately,ICIs are incr...BACKGROUND The development of immune checkpoint inhibitors(ICIs)has heralded a new era in cancer treatment,enabling the possibility of long-term survival in patients with metastatic disease.Unfortunately,ICIs are increasingly implicated in the development of autoimmune diseases.CASE SUMMARY We present a man with squamous cell carcinoma of the oropharynx on a combination of teriprizumab,docetaxel,and cisplatin therapy who developed autoimmune polyendocrine syndrome typeⅡ(APS-2)including thyroiditis and type 1 diabetes mellitus and Crohn’s disease(CD).He developed thirst,abdominal pain,and fatigue after two-week treatment with the protein 1 ligand inhibitor teriprizumab.Biochemistry confirmed APS-2 and thyrotoxicosis.He was commenced on an insulin infusion.However,his abdominal pain persisted.Follow-up surgery confirmed CD and his abdominal pain was relieved by mesalazine.He was continued on insulin and mesalazine therapy.CONCLUSION Immunotherapy can affect all kinds of organs.When clinical symptoms cannot be explained by a single disease,clinicians should consider the possibility of multisystem damage.展开更多
目的:探讨因使用免疫检查点抑制剂(immune checkpoint inhibitors,ICPis)导致ICPis相关性糖尿病患者的临床特点。方法:回顾2例确诊为ICPis相关性糖尿病患者的临床资料,并复习相关文献。结果:2例ICPis相关性糖尿病患者均有肿瘤病史并接受...目的:探讨因使用免疫检查点抑制剂(immune checkpoint inhibitors,ICPis)导致ICPis相关性糖尿病患者的临床特点。方法:回顾2例确诊为ICPis相关性糖尿病患者的临床资料,并复习相关文献。结果:2例ICPis相关性糖尿病患者均有肿瘤病史并接受ICPis治疗,且ICPis治疗前无糖尿病病史。文献报道患者多在使用ICPis治疗后12周,也有在几个月到几年后出现血糖升高。ICPis相关性糖尿病病情进展快,特别在联用细胞毒性T淋巴细胞相关抗原4(cytotoxic T lymphocyte-associated antigen-4,CTLA-4)抗体与程序性死亡受体1(programmed death 1,PD-1)抗体后,病情进展更快。若不及时治疗易发生糖尿病酮症酸中毒。结论:ICPis相关性糖尿病是ICPis罕见但严重的副作用。建议接受ICPis治疗的患者定期监测血糖,尽早筛查可能出现的ICPis相关性糖尿病,及时治疗,改善预后。展开更多
免疫检查点抑制剂(immune-checkpoint inhibitor,ICI)在肿瘤领域的应用取得了突破性进展,但同时也带来了与免疫紊乱相关的、独特的不良反应。1型糖尿病(type l diabetes mellitus,T1DM)是极其罕见的内分泌系统并发症,但目前仍缺乏系统...免疫检查点抑制剂(immune-checkpoint inhibitor,ICI)在肿瘤领域的应用取得了突破性进展,但同时也带来了与免疫紊乱相关的、独特的不良反应。1型糖尿病(type l diabetes mellitus,T1DM)是极其罕见的内分泌系统并发症,但目前仍缺乏系统的研究。本文报道1例二线使用ICI治疗晚期食管鳞癌后出现T1DM的病例。患者为53岁男性,使用抗程序性死亡蛋白1(programmed cell death protein 1,PD-1)单抗后96天出现呕吐、纳差,第102天出现糖尿病酮症酸中毒,C肽水平<0.01 nmol/L,胰岛相关抗体为阴性。同时本文回顾现有文献,总结了T1DM的临床特征、治疗反应以及与疗效的关系,以期提高患者和临床医师对T1DM的警惕性和认知程度。展开更多
This review focuses on the development of hyperglycemia arising from widely used cancer therapies spanning four drug classes.These groups of medications were selected due to their significant association with new onse...This review focuses on the development of hyperglycemia arising from widely used cancer therapies spanning four drug classes.These groups of medications were selected due to their significant association with new onset hyperglycemia,or of potentially severe clinical consequences when present.These classes include glucocorticoids that are frequently used in addition to chemotherapy treatments,and the antimetabolite class of 5-fluorouracil-related drugs.Both of these classes have been in use in cancer therapy since the 1950s.Also considered are the phosphatidyl inositol-3-kinase(PI3K)/AKT/mammalian target of rapamycin(mTOR)-inhibitors that provide cancer response advantages by disrupting cell growth,proliferation and survival signaling pathways,and have been in clinical use as early as 2007.The final class to be reviewed are the monoclonal antibodies selected to function as immune checkpoint inhibitors(ICIs).These were first used in 2011 for advanced melanoma and are rapidly becoming widely utilized in many solid tumors.For each drug class,the literature has been reviewed to answer relevant questions about these medications related specifically to the characteristics of the hyperglycemia that develops with use.The incidence of new glucose elevations in euglycemic individuals,as well as glycemic changes in those with established diabetes has been considered,as has the expected onset of hyperglycemia from their first use.This comparison emphasizes that some classes exhibit very immediate impacts on glucose levels,whereas other classes can have lengthy delays of up to 1 year.A comparison of the spectrum of severity of hyperglycemic consequences stresses that the appearance of diabetic ketoacidosis is rare for all classes except for the ICIs.There are distinct differences in the reversibility of glucose elevations after treatment is stopped,as the mTOR inhibitors and ICI classes have persistent hyperglycemia long term.These four highlighted drug categories differ in their underlying mechanisms driving hyperglycemia,with clinical presentations ranging from potent yet transient insulin resistant states[type 2 diabetes mellitus(T2DM)-like]to rare permanent insulin-deficient causes of hyperglycemia.Knowledge of the relative incidence of new onset hyperglycemia and the underlying causes are critical to appreciate how and when to best screen and treat patients taking any of these cancer drug therapies.展开更多
近年来,免疫检查点抑制剂已成为晚期癌症的重要治疗方法之一,随着免疫检查点抑制剂应用于临床,免疫相关不良反应也随之增多。其中,免疫相关的血糖异常越来越被关注,尤以1型糖尿病(T1DM)危害最大。本文主要综述程序性细胞死亡受体1/程序...近年来,免疫检查点抑制剂已成为晚期癌症的重要治疗方法之一,随着免疫检查点抑制剂应用于临床,免疫相关不良反应也随之增多。其中,免疫相关的血糖异常越来越被关注,尤以1型糖尿病(T1DM)危害最大。本文主要综述程序性细胞死亡受体1/程序性细胞死亡-配体(Programmed cell death 1/Programmed cell death 1 ligand 1,PD-1/PD-L1)抑制剂治疗引起的1型糖尿病的临床特征、发病机制以及诊疗策略等,为肿瘤免疫的安全用药提供参考。展开更多
文摘BACKGROUND The development of immune checkpoint inhibitors(ICIs)has heralded a new era in cancer treatment,enabling the possibility of long-term survival in patients with metastatic disease.Unfortunately,ICIs are increasingly implicated in the development of autoimmune diseases.CASE SUMMARY We present a man with squamous cell carcinoma of the oropharynx on a combination of teriprizumab,docetaxel,and cisplatin therapy who developed autoimmune polyendocrine syndrome typeⅡ(APS-2)including thyroiditis and type 1 diabetes mellitus and Crohn’s disease(CD).He developed thirst,abdominal pain,and fatigue after two-week treatment with the protein 1 ligand inhibitor teriprizumab.Biochemistry confirmed APS-2 and thyrotoxicosis.He was commenced on an insulin infusion.However,his abdominal pain persisted.Follow-up surgery confirmed CD and his abdominal pain was relieved by mesalazine.He was continued on insulin and mesalazine therapy.CONCLUSION Immunotherapy can affect all kinds of organs.When clinical symptoms cannot be explained by a single disease,clinicians should consider the possibility of multisystem damage.
文摘目的:探讨因使用免疫检查点抑制剂(immune checkpoint inhibitors,ICPis)导致ICPis相关性糖尿病患者的临床特点。方法:回顾2例确诊为ICPis相关性糖尿病患者的临床资料,并复习相关文献。结果:2例ICPis相关性糖尿病患者均有肿瘤病史并接受ICPis治疗,且ICPis治疗前无糖尿病病史。文献报道患者多在使用ICPis治疗后12周,也有在几个月到几年后出现血糖升高。ICPis相关性糖尿病病情进展快,特别在联用细胞毒性T淋巴细胞相关抗原4(cytotoxic T lymphocyte-associated antigen-4,CTLA-4)抗体与程序性死亡受体1(programmed death 1,PD-1)抗体后,病情进展更快。若不及时治疗易发生糖尿病酮症酸中毒。结论:ICPis相关性糖尿病是ICPis罕见但严重的副作用。建议接受ICPis治疗的患者定期监测血糖,尽早筛查可能出现的ICPis相关性糖尿病,及时治疗,改善预后。
文摘免疫检查点抑制剂(immune-checkpoint inhibitor,ICI)在肿瘤领域的应用取得了突破性进展,但同时也带来了与免疫紊乱相关的、独特的不良反应。1型糖尿病(type l diabetes mellitus,T1DM)是极其罕见的内分泌系统并发症,但目前仍缺乏系统的研究。本文报道1例二线使用ICI治疗晚期食管鳞癌后出现T1DM的病例。患者为53岁男性,使用抗程序性死亡蛋白1(programmed cell death protein 1,PD-1)单抗后96天出现呕吐、纳差,第102天出现糖尿病酮症酸中毒,C肽水平<0.01 nmol/L,胰岛相关抗体为阴性。同时本文回顾现有文献,总结了T1DM的临床特征、治疗反应以及与疗效的关系,以期提高患者和临床医师对T1DM的警惕性和认知程度。
文摘This review focuses on the development of hyperglycemia arising from widely used cancer therapies spanning four drug classes.These groups of medications were selected due to their significant association with new onset hyperglycemia,or of potentially severe clinical consequences when present.These classes include glucocorticoids that are frequently used in addition to chemotherapy treatments,and the antimetabolite class of 5-fluorouracil-related drugs.Both of these classes have been in use in cancer therapy since the 1950s.Also considered are the phosphatidyl inositol-3-kinase(PI3K)/AKT/mammalian target of rapamycin(mTOR)-inhibitors that provide cancer response advantages by disrupting cell growth,proliferation and survival signaling pathways,and have been in clinical use as early as 2007.The final class to be reviewed are the monoclonal antibodies selected to function as immune checkpoint inhibitors(ICIs).These were first used in 2011 for advanced melanoma and are rapidly becoming widely utilized in many solid tumors.For each drug class,the literature has been reviewed to answer relevant questions about these medications related specifically to the characteristics of the hyperglycemia that develops with use.The incidence of new glucose elevations in euglycemic individuals,as well as glycemic changes in those with established diabetes has been considered,as has the expected onset of hyperglycemia from their first use.This comparison emphasizes that some classes exhibit very immediate impacts on glucose levels,whereas other classes can have lengthy delays of up to 1 year.A comparison of the spectrum of severity of hyperglycemic consequences stresses that the appearance of diabetic ketoacidosis is rare for all classes except for the ICIs.There are distinct differences in the reversibility of glucose elevations after treatment is stopped,as the mTOR inhibitors and ICI classes have persistent hyperglycemia long term.These four highlighted drug categories differ in their underlying mechanisms driving hyperglycemia,with clinical presentations ranging from potent yet transient insulin resistant states[type 2 diabetes mellitus(T2DM)-like]to rare permanent insulin-deficient causes of hyperglycemia.Knowledge of the relative incidence of new onset hyperglycemia and the underlying causes are critical to appreciate how and when to best screen and treat patients taking any of these cancer drug therapies.
文摘近年来,免疫检查点抑制剂已成为晚期癌症的重要治疗方法之一,随着免疫检查点抑制剂应用于临床,免疫相关不良反应也随之增多。其中,免疫相关的血糖异常越来越被关注,尤以1型糖尿病(T1DM)危害最大。本文主要综述程序性细胞死亡受体1/程序性细胞死亡-配体(Programmed cell death 1/Programmed cell death 1 ligand 1,PD-1/PD-L1)抑制剂治疗引起的1型糖尿病的临床特征、发病机制以及诊疗策略等,为肿瘤免疫的安全用药提供参考。
