BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there are no definitive biomarkers for late risk leucopenia prediction.AIM To determine the predictive value of early monitoring of DNA-thioguanine(DNATG)or 6-thioguanine nucleotides(6TGN)for late leucopenia under a NUDT15-guided thiopurine dosing strategy in patients with Crohn’s disease(CD).METHODS Blood samples were collected within two months after thiopurine initiation for detection of metabolite concentrations.Late leucopenia was defined as a leukocyte count<3.5×10^(9)/L over two months.RESULTS Of 148 patients studied,late leucopenia was observed in 15.6%(17/109)of NUDT15/thiopurine methyltransferase(TPMT)normal and 64.1%(25/39)of intermediate metabolizers.In patients suffering late leucopenia,early DNATG levels were significantly higher than in those who did not develop late leucopenia(P=4.9×10^(-13)).The DNATG threshold of 319.43 fmol/μg DNA could predict late leucopenia in the entire sample with an area under the curve(AUC)of 0.855(sensitivity 83%,specificity 81%),and in NUDT15/TPMT normal metabolizers,the predictive performance of a threshold of 315.72 fmol/μg DNA was much more remarkable with an AUC of 0.902(sensitivity 88%,specificity 85%).6TGN had a relatively poor correlation with late leucopenia whether in the entire sample(P=0.021)or NUDT15/TPMT normal or intermediate metabolizers(P=0.018,P=0.55,respectively).CONCLUSION Proactive therapeutic drug monitoring of DNATG could be an effective strategy to prevent late leucopenia in both NUDT15/TPMT normal and intermediate metabolizers with CD,especially the former.
Epstein-Barr virus (EBV) mucocutaneous ulceration is a rare complication of immunosuppression that results in painful ulceration of the tongue or gingiva, and less commonly, refractory ulceration of the gastrointestinal tract. High clinical suspicion is required, as failure to diagnose EBV mucocutaneous ulceration may result in significant morbidity and mortality. We report the case of a 64-year-old female renal transplant recipient requiring admission to hospital for management of severe oral and epigastric pain. Examination revealed a large, superficial, well-circumscribed ulcer at the base of the tongue. Blood tests suggested a secondary immunodeficiency characterised by mild leucopenia, hypogammaglobulinaemia, and low memory B-cells with normal immunophenotype. Endoscopy revealed four, cratered ulcers in the pre-pyloric region of the stomach. A core biopsy of the tongue ulcer confirmed EBV mucocutaneous ulceration. The patient’s immunosuppression was optimised, which resulted in complete resolution of the tongue and gastric ulcers at eight and twelve weeks of follow-up respectively.
