Leukopenia due to <i>Parvovirus B19</i> in a Crohn's Disease Patient Using Azathioprine

Abstract

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 parvovirusB19 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. ParvovirusB19 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 parvovirusB19 infection and compels temporal but not permanent cessation of thiopurine therapy.

Identification of Patients With Variants in TPMT and Dose Reduction Reduces Hematologic Events During Thiopurine Treatment of Inflammatory Bowel Disease

“…21 Finally, co-medication might make patients more susceptible for leucopenia. 27 For this reason, we excluded patients receiving allopurinol as co-medication. 28 However, other commonly used treatments for IBD, e.g.…”

Risk factors for thiopurine‐induced myelosuppression and infections in inflammatory bowel disease patients with a normal TPMT genotype

“…This comes with some restrictions, since exacerbations of IBD or flu‐like side effects (which might include elevation of C‐reactive protein) can mimic (gastro‐intestinal) infections leading to the prescription of antibiotics. Finally, (viral) infections may induce leucopenia . However, if this is the case it would have resulted in an overestimation of ‘leucopenia‐associated infections’ and further bolster our findings that (moderate) leucopenia itself is not a risk factor for infectious complications.…”

“…However, only up to 25% of the leucopenia cases can be explained by variants in TPMT , which makes that leucopenia is frequently observed in patients without a TPMT variant . This suggests that also other genes and environmental or clinical factors may contribute to the risk of leucopenia during thiopurine treatment …”

Azathioprine versus mesalazine for prevention of postoperative clinical recurrence in patients with Crohn's disease with endoscopic recurrence: efficacy and safety results of a randomised, double-blind, double-dummy, multicentre trial

“…Taken together, these pharmacogenetic data support the view that TPMT testing could help to avoid azathioprine-related haematotoxicity. It is clear, however, that TPMT testing cannot explain all cases of leucopenia observed in azathioprine-treated patients since other possible underlying mechanisms, such as drug transport proteins (eg, MRP434), other thiopurine-related enzymes (eg, ITPase35 36) and viral infections,37 may contribute to the onset of adverse drug reactions.…”