Fatal myelotoxicity after azathioprine treatment.
Azathioprine and 6-mercaptopurine have been used for many years in the treatment of inflammatory bowel disease. Approximately 0.3% of the population are homozygous for variant alleles associated with extremely low thiopurine S-methyltransferase enzyme activity. We describe the case of a young patient with ulcerative colitis, homozygous for TPMT*3A alleles, who suffered fatal azathioprine-induced myelotoxicity after standard dosing with azathioprine. Screening for decreased activity of TPMT in patients prior to azathioprine treatment is advised to minimize the risk of drug-induced toxicity.
Slanar
O
O
Clinical Pharmacology Unit, Department of Pharmacology, First Faculty of Medicine Charles University, General Teaching Hospital, Prague, Czech Republic. oslan@lf1.cuni.cz
Chalupná
P
P
Novotný
A
A
Bortlík
M
M
Krska
Z
Z
Lukás
M
M
D000328:Adult; D001379:Azathioprine / Q000009:adverse effects* / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects*; D003093:Colitis, Ulcerative / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D064420:Drug-Related Side Effects and Adverse Reactions; D017809:Fatal Outcome; D005738:Gas Gangrene / Q000150:complications / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology; D006720:Homozygote; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000172:deficiency / Q000235:genetics; D010198:Pancytopenia / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000473:pathology
D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine