title: Azathioprine-induced fatal myelosuppression in systemic lupus erythematosus patient carrying TPMT*3C polymorphism.
abstract: Azathioprine (AZA) is a commonly used immunosuppressant for systemic lupus erythematosus (SLE). Myelosuppression is a serious adverse reaction due to AZA and its metabolites. Thiopurine S-methyltransferase (TPMT) is the rate-limiting enzyme. Variations of TPMT enzyme activity may be responsible for myelosuppression. However, a correlation between certain mutant alleles of low TPMT enzyme activity and myelotoxicity has also been suggested as a factor. We describe herein a case of AZA-induced severe myelosuppression associated with TPMT*3C heterozygous mutant allele in a SLE patient. The patient presented with pancytopenia, sepsis, typhlitis and disseminated intravascular coagulopathy after a short period of AZA therapy. The patient had low TPMT activity and TPMT*3C genotype. Measurement of TPMT activity and determination of TPMT variant allele may identify patients at risk for AZA-induced myelosuppression.
authors.affiliation: Lupus Research Unit, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand..
authors.forename: U
authors.initials: U
authors.lastname: Boonsrirat
authors.forename: S
authors.initials: S
authors.lastname: Angsuthum
authors.forename: S
authors.initials: S
authors.lastname: Vannaprasaht
authors.forename: J
authors.initials: J
authors.lastname: Kongpunvijit
authors.forename: N
authors.initials: N
authors.lastname: Hirankarn
authors.forename: W
authors.initials: W
authors.lastname: Tassaneeyakul
authors.forename: Y
authors.initials: Y
authors.lastname: Avihingsanon
mesh_terms: D000328:Adult; D000483:Alleles; D001379:Azathioprine / Q000009:adverse effects* / Q000627:therapeutic use; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007970:Leukopenia / Q000139:chemically induced*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000235:genetics; D008780:Methyltransferases / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D007166:Immunosuppressive Agents; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine