Azathioprine-induced severe cholestatic hepatitis in patient carrying TPMT*3C polymorphism.
METHODS
A 40-year-old man with pemphigus foliaceus developed a jaundice and pruritus three weeks after starting azathioprine 100 mg daily. Laboratory investigations revealed a severe cholestatic hepatitis. Azathioprine-induced hepatitis was suspected. The dosage of thiopurine methyltransferase activity showed a low activity of the enzyme and the genotype of this enzyme found a TPMT*3C heterozygous mutant allele. Azathioprine was withdrawn. The icterus regressed progressively and the hepatic tests normalised slowly. The patient had no further episodes of hepatitis over a follow-up period of 6 months.


CONCLUSIONS
Although, hematotoxicity seems to be associated with homozygous TPMT variants, a possible association between azathioprine hepatotoxicity and a TPMT*3C genotype should be investigated further.
Ben Salem
Chaker
C
Department of Clinical Pharmacology, Faculty of Medicine of Sousse, Avenue Mohamed Karoui, 4002, Sousse, Tunisia. bensalem.c@gmail.com
Ben Salah
Lynda
L
Belajouza
Colandane
C
Bouraoui
Kamel
K
D000328:Adult; D001379:Azathioprine / Q000009:adverse effects*; D002780:Cholestasis, Intrahepatic / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics*; D005500:Follow-Up Studies; D006580:Genetic Carrier Screening / Q000379:methods; D006579:Heterozygote; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012720:Severity of Illness Index
D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine