Yeungnam Univ J Med.  2020 Oct;37(4):332-336. 10.12701/yujm.2020.00178.

Prevention of thiopurine-induced early leukopenia in a Korean pediatric patient with Crohn’s disease who turned out to possess homozygous mutations in NUDT15 R139C

• Bae J
• Choe BH
• Kang B

• KMID: 2508180
• DOI: http://doi.org/10.12701/yujm.2020.00178

Abstract

Homozygous mutations in NUDT15 R139C are known as the major factor associated with thiopurine-induced early leukopenia, particularly in Asian patients. Therefore, NUDT15 genotyping is currently recommended before thiopurine treatment to identify patients who are NUDT15 poor metabolizers and consider the use of an alternative immunomodulatory therapy. We report a case of a 12-year-old Korean girl with Crohn’s disease (CD), in whom thiopurine-induced leukopenia was prevented by initiation of azathioprine (AZA) therapy at a low dose (0.5 mg/kg/day) and early detection of significant hair loss and white blood cell (WBC) count decrease at 17 days from the start of AZA treatment. The WBC count dropped from 8,970/μL to 3,370/μL in 2 weeks, and AZA treatment was stopped because of concerns of potential leukopenia in the near future. Her WBC count recovered to 5,120/μL after 3 weeks. Gene analysis later revealed that she had a homozygous mutation in NUDT15 R139C, resulting in a poor metabolizing activity of NUDT15. In situations when NUDT15 genotyping is unavailable, initiation of AZA therapy at 0.5 mg/kg/day with close observation of hair loss and WBC counts within 2 weeks may be an alternative way to prevent thiopurine-induced early leukopenia in Asian children with CD.

Keyword

Alopecia; Azathioprine; Inflammatory bowel disease; Leukopenia; NUDT15

Figure

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  Fig. 1. Endoscopic images at diagnosis. Multiple ulcers of various sizes are noted in the terminal ileum (A) and colon (B).

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  Fig. 2. Changes in white blood cell counts after the initiation and discontinuation of azathioprine in the patient. AZA, azathioprine; WBC, white blood cell.

Reference

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