Thioguanine nucleotides and thiopurine methyltransferase in immunobullous diseases: optimal levels as adjunctive tools for azathioprine monitoring.
OBJECTIVE
To prospectively determine optimal levels of 6-thioguanine nucleotide for disease remission in patients with immunobullous disease treated with azathioprine.


METHODS
Prospective, longitudinal study. Laboratory tests and clinical evaluations were performed monthly for 6 months and then every 2 to 3 months (median follow-up, 13.4 months).


METHODS
Tertiary care medical center.


METHODS
Twenty-seven patients with immunobullous disease treated with azathioprine were enrolled during a 2-year period. Twelve met the criteria for evaluation of optimal levels of 6-thioguanine nucleotide.


METHODS
Blood levels of 6-thioguanine nucleotide, 6-methylmercaptopurine, and thiopurine methyltransferase by polymerase chain reaction and enzyme activity were measured longitudinally during treatment.


RESULTS
The range of 6-thioguanine nucleotide was 48 to 457 pmol/8 x 10(8) red blood cells (RBCs), with an average optimal level of 190.7 pmol/8 x 10(8) RBCs for all patients. The mean optimal levels were 179.4 and 205.6 pmol/8 x 10(8) RBCs for pemphigus and pemphigoid, respectively. Limited disease required less 6-thioguanine, with a mean of 145.3 pmol/8 x 10(8) RBCs. Longitudinal induction of thiopurine methyltransferase activity was observed during treatment. Patients with recalcitrant disease showed higher induction of enzyme activity (with an increase of 9.1 to 23.6 U/mL of RBCs above baseline) than did those with responsive disease.


CONCLUSIONS
Optimal levels of 6-thioguanine nucleotide metabolites for disease remission in dermatology patients are 150 to 300 pmol/8 x 10(8) RBCs. High levels of the inactive metabolite 6-methylmercaptopurine and induction of thiopurine methyltransferase are associated with recalcitrant disease.
el-Azhary
Rokea A
RA
Department of Dermatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA. elazhary.rokea2@mayo.edu
Farmer
Sara A
SA
Drage
Lisa A
LA
Rogers
Roy S
RS
McEvoy
Marian T
MT
Davis
Mark D P
MD
Bridges
Alina G
AG
Gibson
Lawrence E
LE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001379:Azathioprine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D020714:Maximum Tolerated Dose; D008780:Methyltransferases / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D010392:Pemphigus / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D013866:Thioguanine / Q000378:metabolism*; D016896:Treatment Outcome
D008780:Methyltransferases; C022745:thiopurine methyltransferase; D013866:Thioguanine; D001379:Azathioprine