Azathioprine as a treatment for severe atopic eczema in children with a partial thiopurine methyl transferase (TPMT) deficiency.
Azathioprine is a valuable agent in the treatment of severe childhood atopic eczema. Thiopurine methyl transferase (TPMT) exhibits autosomal codominant polymorphism and plays an important role in the metabolism of azathioprine. In most large population groups studied to date, approximately 10% of the population had intermediate activity due to heterozygosity at the TPMT locus, and about 0.33% were TPMT deficient. TPMT deficiency results in the accumulation of thioguanine nucleotides and cytotoxic 6-mercaptopurine metabolites. Previously it was considered unsafe to treat this group with azathioprine because of what was considered to be an unacceptably high risk of toxicity (profound myelosuppression). Better understanding of the pharmacogenetics of purine metabolism has changed this, and with appropriate dose adjustments, individuals who have a partial TPMT deficiency (heterozygotes) can now be treated with thiopurines. It seems probable that these individuals are more likely to have a therapeutic response while being at lower risk of developing dose-related hepatotoxicity because of the reduced doses required to effect a therapeutic response. Two patients with severe refractory atopic eczema, both of whom had a partial TPMT deficiency, have had an excellent response to treatment with azathioprine. They were treated with half-standard doses and response to treatment occurred within 2 weeks.
Murphy
Lesley-Ann
LA
St. Johns Institute of Dermatology, London, United Kingdom. lammurphy@yahoo.com
Atherton
David J
DJ
D000284:Administration, Oral; D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D001379:Azathioprine / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000473:pathology; D003937:Diagnosis, Differential; D004485:Eczema / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000172:deficiency*; D012720:Severity of Illness Index
D000964:Antimetabolites, Antineoplastic; D008780:Methyltransferases; D001379:Azathioprine