Azathioprine and its initial metabolite, 6-mercaptopurine (6-MP), are associated with high rates of treatment cessation due to toxicity or inadequate response. Individualization of thiopurine dose based on concentrations of the active 6-thioguanine nucleotide (6-TGN) metabolites can help improve outcomes with this class. Some individuals, however, preferentially metabolize thiopurine drugs to the potentially hepatotoxic 6-methylmercaptopurine nucleotide (6-MMPN) metabolites rather than the 6-TGNs. For these patients, escalation in thiopurine dose is not likely to increase 6-TGN concentrations sufficiently but may lead to a disproportionate increase in exposure to the 6-MMPNs. We present three cases in whom thiopurine dose escalation based on clinical status and low 6-TGN concentrations (100-262 pmol/8 x 10 RBC) resulted in severe hepatotoxicity (liver failure in two cases) associated with unrecognized extremely high 6-MMPN concentrations of 26,000-40,000 pmol/8 x 10 RBC. These cases illustrate a risk with thiopurine dose adjustment based on monitoring of 6-TGN metabolites without also monitoring 6-MMPN.

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IntroductionBurkitt lymphoma and B cell lymphomas in childhood may arise in many atypical locations, which on rare occasions can include gastric mucosa. A case of primary gastric Burkitt lymphoma is described in a child presenting as a protein-losing enteropathy, including the direct monitoring of the disease response by sequential endoscopic biopsy and molecular analysis.Case presentationWe report a 9-year-old boy who presented with gross oedema, ascites and respiratory distress caused by a protein-losing enteropathy. Initial imaging investigations were non-diagnostic but gastroduodenal endoscopy revealed massive involvement of the gastric mucosa with a primary Burkitt lymphoma. His subsequent clinical progress and disease response were monitored directly by endoscopy and he remains in clinical remission 4 years after initial diagnosis.ConclusionsThis is the first case report of primary Burkitt lymphoma presenting as a protein-losing enteropathy. The clinical course and progress of the patient were monitored by sequential endoscopic biopsy, histology and molecular analysis by fluorescence in situ hybridisation.

Background The utility of risk scoring systems has not been validated in hospitalised patients who develop upper gastrointestinal bleeding (UGIB). This study's aim is to compare the accuracy of different risk scoring systems in these patients. Methods Consecutive hospitalised patients who developed UGIB were included. Patients who had onset of UGIB less than 24 hours from the time of admission were excluded. UGIB risk assessment scores (Glasgow Blatchford, AIMS65, ABC, full Rockall, admission Rockall and PNED scores) were calculated and their abilities to predict predefined clinical endpoints: 30‐day mortality, endoscopic intervention and a composite endpoint (30‐day mortality or endoscopic intervention) were compared using area under the receiver operating curve (AUROC). Results A total of 229 patients were included. Forty‐six (20%) required endoscopic intervention and 35 (15%) died within 30 days. The ABC score accurately predicted 30‐day mortality (AUROC 0.85) compared to PNED score (AUROC 0.80, P = 0.22), full Rockall score (AUROC 0.75, P < 0.05), Glasgow Blatchford score (AUROC 0.71, P < 0.05) and AIMS65 score (AUROC 0.70, P < 0.05). Patients with an ABC score ≤ 3 had a 30‐day mortality rate of 1.6%, compared to 7.5% and 42% for scores of 4‐7 and ≥ 8 respectively. None of the scores accurately predicted the need for endoscopic intervention and the composite endpoint (30‐day mortality or need for endoscopic intervention) (all scores AUROC < 0.8). Conclusions In conclusion, the ABC score was most accurate at predicting mortality in hospitalised patients who develop UGIB making it clinically useful in all patients with UGIB.