Bone Marrow Aplasia and Neutropenic Fever Following Azathioprine Dose Escalation in a TPMT-Deficient Patient with Crohn's Disease and Psoriatic Arthritis-A CARE-Compliant Case.

IF 1.7 Q2 MEDICINE, GENERAL & INTERNAL
Krzysztof Wroński, Michał Tadeusz Holecki, Natalia Boguszewska, Marzena Skrzypczak-Zielińska, Jerzy Tadeusz Chudek
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Abstract

Background: Myelotoxicity, usually manifested by moderate leukopenia (particularly neutropenia), is a well-known adverse drug reaction to azathioprine (AZA) therapy. Thiopurine methyltransferase (TMPT) and nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) genotyping are not routinely performed in patients starting AZA therapy due to their low cost-effectiveness. Additionally, the concomitant use of xanthine oxidase inhibitors and 5-aminosalicylates may slow the metabolism of 6-mercaptopurine. Case Description: We describe a case of a 26-year-old Caucasian man with Crohn's disease and psoriatic arthritis treated with mesalazine and AZA (100 mg daily) who developed prolonged bone marrow aplasia and neutropenic fever after increasing the daily dose of AZA from 100 to 150 mg (from 44 to 66 mg/m2), without frequent total blood count monitoring. Discontinuation of AZA, multiple transfusions of red blood cells and platelet concentrate, filgrastim, empirical antibiotic therapy, and antiviral and antifungal prophylaxis were obtained after 11 days complete recovery of bone marrow aplasia. Methods: Genomic DNA genotyping of coding regions of TPMT (exons 2-9) and NUDT15 (exons 1-3). Results: Heterozygous alleles in the untranslated region (c.460G>A and c.719A>G) associated with TPMT deficiency and a benign variant (c.*7G>A) in the 3'-UTR of NUDT15 with no effect on enzyme activity were found. Conclusions: This case highlights the importance of monitoring the total blood count frequently during the first weeks of treatment with moderate-to-high doses of AZA. Furthermore, the interaction between AZA and mesalazine may play a significant role in the development of prolonged bone marrow aplasia.

骨髓发育不全和中性粒细胞减少热后硫唑嘌呤剂量增加的tpmt缺陷患者克罗恩病和银屑病关节炎-护理依从病例。
背景:骨髓毒性通常表现为中度白细胞减少(特别是中性粒细胞减少),是硫唑嘌呤(AZA)治疗的一种众所周知的不良药物反应。硫嘌呤甲基转移酶(TMPT)和核苷二磷酸连接片段x型基序15 (NUDT15)基因分型在开始AZA治疗的患者中不常规进行,因为它们的成本效益较低。此外,同时使用黄嘌呤氧化酶抑制剂和5-氨基水杨酸可能会减缓6-巯基嘌呤的代谢。病例描述:我们描述了一例26岁的患有克罗恩病和银屑病关节炎的高加索男性患者,用美萨拉嗪和AZA(每天100毫克)治疗,在将AZA的每日剂量从100毫克增加到150毫克(从44毫克增加到66毫克/平方米)后,出现了延长的骨髓发育不全和中性粒细胞减少热,没有经常监测总血细胞计数。骨髓发育不全完全恢复11天后停用AZA、多次输注红细胞和浓缩血小板、非格昔汀、经经验抗生素治疗、抗病毒和抗真菌预防。方法:对TPMT(2-9外显子)和NUDT15(1-3外显子)的编码区进行基因组DNA分型。结果:在NUDT15的3′-UTR区发现与TPMT缺乏相关的非翻译区杂合等位基因(c. 460g >A和c. 719a >G)和良性变异(c.*7G>A),对酶活性无影响。结论:本病例强调了在使用中至高剂量AZA治疗的头几周频繁监测总血细胞计数的重要性。此外,AZA与美沙拉嗪的相互作用可能在延长骨髓发育不全的发展中起重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Clinics and Practice
Clinics and Practice MEDICINE, GENERAL & INTERNAL-
CiteScore
2.60
自引率
4.30%
发文量
91
审稿时长
10 weeks
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