Oral azathioprine for recalcitrant pediatric atopic dermatitis: clinical response and thiopurine monitoring.
BACKGROUND
Azathioprine is prescribed as a corticosteroid-sparing agent for many inflammatory conditions, including refractory atopic dermatitis (AD). There are limited prospective data on its appropriate use and monitoring for children with AD.


OBJECTIVE
This study was designed to assess clinical response to azathioprine, determine the necessity for repeated measurement of thiopurine methyltransferase (TPMT) activity during treatment, and test the utility of measuring levels of the metabolites 6-thioguanine nucleotide and 6-methylmercaptopurine.


METHODS
Twelve children with severe, recalcitrant AD were treated with oral azathioprine and followed prospectively. Disease severity was determined by the SCORing AD index. Baseline TPMT activity was measured and this was repeated along with 6-thioguanine nucleotide and 6-methylmercaptopurine measurement at times of stable improvement, inadequate response, or change in response.


RESULTS
Azathioprine therapy was associated with clinical improvement in all but 1 patient. There were few adverse effects. Three patients showed a significant change in TPMT activity during treatment: 2 had a mild decrease and 1 demonstrated enzyme inducibility with an increase from the intermediate to the normal activity range. These changes, but not 6-thioguanine nucleotide or 6-methylmercaptopurine levels, inversely correlated with the clinical response to therapy.


CONCLUSIONS
Small sample size is a limitation.


CONCLUSIONS
Azathioprine can be of benefit in the treatment of recalcitrant pediatric AD. Repeat assessment of TPMT activity may be helpful for evaluation of nonresponse or change in response and warrants further study. In contrast, measurement of thiopurine metabolites during treatment was not clinically useful.
Georgetown University School of Medicine, Washington, District of Columbia, USA.
Maura
M
Caufield
Wynnis L
WL
Tom
D000284:Administration, Oral; D000293:Adolescent; D001379:Azathioprine / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D005260:Female; D006150:Guanine Nucleotides / Q000097:blood; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D015122:Mercaptopurine / Q000031:analogs & derivatives / Q000097:blood; D008780:Methyltransferases / Q000097:blood*; D011446:Prospective Studies; D012720:Severity of Illness Index; D013873:Thionucleotides / Q000097:blood
D006150:Guanine Nucleotides; D007166:Immunosuppressive Agents; D013873:Thionucleotides; C003964:6-thioguanylic acid; C010240:6-methylthiopurine; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine