title: Azathioprine and diffuse alveolar haemorrhage: the pharmacogenetics of thiopurine methyltransferase.
abstract: Current guidelines support the use of corticosteroids and azathioprine as one possible treatment strategy for idiopathic pulmonary fibrosis (IPF). However, some patients with genetic polymorphisms of thiopurine methyltransferase (TPMT) are at risk of severe azathioprine myelotoxicity. The current authors present the case of an 85-yr-old Caucasian male with IPF who developed diffuse alveolar haemorrhage as a complication of azathioprine-induced myelosuppression. Leukocyte genetic TPMT testing revealed that the patient had homozygous polymorphisms associated with the absence of TPMT activity and severe azathioprine-induced myelotoxicity. Thiopurine methyltransferase deficiency should be considered in patients who develop leukopenia early in treatment with azathiopurine, or who present with severe marrow suppression at usual doses. For centres with equipped laboratories, a dosing suggestion is provided based on thiopurine methyltransferase testing. Even with screening strategies, frequent monitoring of complete blood count and liver biochemistry should remain the mainstay of surveillance for azathioprine toxicity.
authors.affiliation: Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Perri
authors.forename: D E C
authors.initials: DE
authors.lastname: Cole
authors.forename: O
authors.initials: O
authors.lastname: Friedman
authors.forename: E
authors.initials: E
authors.lastname: Piliotis
authors.forename: S
authors.initials: S
authors.lastname: Mintz
authors.forename: N K J
authors.initials: NK
authors.lastname: Adhikari
mesh_terms: D001379:Azathioprine / Q000009:adverse effects*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000201:enzymology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008171:Lung Diseases / Q000139:chemically induced* / Q000201:enzymology; D008297:Male; D008780:Methyltransferases / Q000172:deficiency / Q000235:genetics*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011658:Pulmonary Fibrosis / Q000188:drug therapy / Q000235:genetics
chemical_list: D007166:Immunosuppressive Agents; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine