Wroński Krzysztof, Holecki Michał Tadeusz, Boguszewska Natalia, Skrzypczak-Zielińska Marzena, Chudek Jerzy Tadeusz
Department of Internal Medicine and Oncological Chemotherapy, Faculty of Medical Sciences in Katowice, Medical University of Silesia in Katowice, 40-029 Katowice, Poland.
Department of Internal Medicine and Metabolic Diseases, Faculty of Medical Sciences in Katowice, Medical University of Silesia in Katowice, 40-752 Katowice, Poland.
Clin Pract. 2025 Jun 19;15(6):114. doi: 10.3390/clinpract15060114.
Myelotoxicity, usually manifested by moderate leukopenia (particularly neutropenia), is a well-known adverse drug reaction to azathioprine (AZA) therapy. Thiopurine methyltransferase () and nucleoside diphosphate-linked moiety X-type motif 15 ( 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. 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/m), 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. Genomic DNA genotyping of coding regions of (exons 2-9) and (exons 1-3). 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 with no effect on enzyme activity were found. 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.
骨髓毒性通常表现为中度白细胞减少（尤其是中性粒细胞减少），是硫唑嘌呤（AZA）治疗众所周知的药物不良反应。由于成本效益低，开始接受AZA治疗的患者通常不常规进行硫嘌呤甲基转移酶（TPMT）和核苷二磷酸连接部分X型基序15（NUDT15）基因分型。此外，同时使用黄嘌呤氧化酶抑制剂和5-氨基水杨酸酯可能会减缓6-巯基嘌呤的代谢。我们描述了一例26岁患有克罗恩病和银屑病关节炎的白人男性患者，该患者接受美沙拉嗪和AZA（每日100mg）治疗，在将AZA每日剂量从100mg增加至150mg（从44mg/m²增至66mg/m²）后，出现了长时间的骨髓再生障碍和中性粒细胞减少性发热，且未频繁监测全血细胞计数。停用AZA、多次输注红细胞和血小板浓缩物、使用非格司亭、经验性抗生素治疗以及进行抗病毒和抗真菌预防后，骨髓再生障碍在11天后完全恢复。对TPMT（外显子2 - 9）和NUDT15（外显子1 - 3）编码区进行基因组DNA基因分型。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）以及NUDT15 3'-UTR中的一个对酶活性无影响的良性变异（c.*7G>A）。该病例强调了在中高剂量AZA治疗的最初几周频繁监测全血细胞计数的重要性。此外，AZA与美沙拉嗪之间的相互作用可能在长时间骨髓再生障碍的发生中起重要作用。
