title: Thioguanine nucleotides and thiopurine methyltransferase in immunobullous diseases: optimal levels as adjunctive tools for azathioprine monitoring.
abstract: 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.
authors.affiliation: Department of Dermatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA. elazhary.rokea2@mayo.edu
authors.forename: Rokea A
authors.initials: RA
authors.lastname: el-Azhary
authors.forename: Sara A
authors.initials: SA
authors.lastname: Farmer
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Drage
authors.forename: Roy S
authors.initials: RS
authors.lastname: Rogers
authors.forename: Marian T
authors.initials: MT
authors.lastname: McEvoy
authors.forename: Mark D P
authors.initials: MD
authors.lastname: Davis
authors.forename: Alina G
authors.initials: AG
authors.lastname: Bridges
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Gibson
mesh_terms: 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
chemical_list: D008780:Methyltransferases; C022745:thiopurine methyltransferase; D013866:Thioguanine; D001379:Azathioprine