van Asseldonk Dirk P, Kanis Bernardina M, de Boer Nanne K H, van Bodegraven Ad A
Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.
Digestion. 2009;79(4):211-4. doi: 10.1159/000212778. Epub 2009 Apr 22.
Thiopurines such as azathioprine (AZA) and 6-mercaptopurine are frequently used for the treatment of inflammatory bowel diseases. Patients with low or absent thiopurine S-methyltransferase (TPMT) activity, resulting in high 6-thioguanine nucleotide levels, have an increased risk of developing leukopenia. Alternatively, certain viral infections could induce leukopenia. We present the case of an adult Crohn's disease patient with a parvovirus B19 infection and leukopenia during long-term AZA therapy. The uncomplicated long-term use of adequately-dosed AZA and stable non-toxic metabolite levels could not acknowledge TPMT deficiency as a primary cause of the leukopenia. parvovirus B19 was assumed to induce the leukopenia by restraining myeloid proliferation. In addition, AZA probably potentiated susceptibility to this viral infection and may have inhibited adequate immunological defense. Leukopenia during thiopurine therapy not explained by TPMT deficiency could be induced by parvovirus B19 infection and compels temporal but not permanent cessation of thiopurine therapy.
硫唑嘌呤(AZA)和6-巯基嘌呤等硫嘌呤类药物常用于治疗炎症性肠病。硫嘌呤甲基转移酶(TPMT)活性低或缺乏的患者,会导致6-硫鸟嘌呤核苷酸水平升高,发生白细胞减少症的风险增加。另外,某些病毒感染也可能诱发白细胞减少症。我们报告了1例成年克罗恩病患者,在长期使用AZA治疗期间感染细小病毒B19并出现白细胞减少症。长期无并发症地使用适当剂量的AZA且代谢产物水平稳定无毒,这并不支持TPMT缺乏是白细胞减少症的主要原因。推测细小病毒B19通过抑制骨髓增殖诱发白细胞减少症。此外,AZA可能增强了对这种病毒感染的易感性,并且可能抑制了充分的免疫防御。硫嘌呤治疗期间由TPMT缺乏无法解释的白细胞减少症可能由细小病毒B19感染诱发,这迫使暂时而非永久性地停止硫嘌呤治疗。