Division of Pediatric Emergency, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Medicine (Baltimore). 2022 Aug 19;101(33):e29986. doi: 10.1097/MD.0000000000029986.
Azathioprine is a purine analog (PA) used to treat myasthenia gravis (MG). However, some patients are sensitive to azathioprine and develop severe side effects, such as leukopenia, alopecia, and diarrhea soon after using the medication. Pharmacogenetics plays a crucial role in such intolerance.
A 16-year-old woman with MG developed hair loss, pancytopenia, bloody diarrhea, and fever shortly after azathioprine treatment.
Pharmacogenetic analysis revealed compound heterozygosity of the nudix hydrolase 15 (NUDT15) gene, which led to suppressed NUDT15 function. Colonoscopy revealed large ulcers with polypoid lesions in the terminal ileum, cecum, ascending colon, and rectum. These are the characteristics of inflammatory bowel disease (IBD).
Sanger sequencing of NUDT15 gene and colonoscopy for bloody stool evaluation.
The patient recovered completely from this acute episode after discontinuation of azathioprine treatment. Her hemogram turned back to normal range. There was also no blood in stool during follow-up.
Pharmacogenetic effects should be considered when prescribing PA medication. The possibility of secondary or concomitant autoimmune diseases must always be considered in patients with MG.
巯嘌呤是一种用于治疗重症肌无力（MG）的嘌呤类似物（PA）。然而，一些患者对巯嘌呤敏感，在使用药物后不久会出现严重的副作用，如白细胞减少症、脱发和腹泻。药物遗传学在这种不耐受中起着至关重要的作用。
一名 16 岁的 MG 女性患者在使用巯嘌呤治疗后不久出现脱发、全血细胞减少、血性腹泻和发热。
药物遗传学分析显示 15 号 nudix 水解酶（NUDT15）基因的复合杂合性，导致 NUDT15 功能受到抑制。结肠镜检查显示末端回肠、盲肠、升结肠和直肠有大的溃疡伴息肉样病变。这些是炎症性肠病（IBD）的特征。
对 NUDT15 基因进行 Sanger 测序和结肠镜检查以评估血性腹泻。
该患者在停止使用巯嘌呤治疗后，急性发作完全恢复。她的血象恢复正常范围。在随访期间，粪便中也没有血液。
在开具 PA 药物时应考虑药物遗传学效应。在 MG 患者中，必须始终考虑继发或伴发自身免疫性疾病的可能性。
