mercaptopurine and Dermatitis--Atopic

For adults with atopic dermatitis (AD) refractory to topical treatment, the choices of second-line therapy are limited. Furthermore, there are concerns about the long-term safety of treatments such as cyclosporin. Limited open studies suggest that azathioprine may be effective, although controlled trial data is lacking. Nevertheless, many UK dermatologists use azathioprine to treat patients with severe AD, despite the potential risk of serious toxicity. Azathioprine myelotoxicity and drug efficacy are now known to be related to the activity of a key enzyme in azathioprine metabolism, thiopurinemethyltransferase (TPMT). Recently, the facility for TPMT measurement has become more widely available, providing the possibility to optimize the therapeutic effect of azathioprine, yet minimise the risk of toxicity. We review the evidence concerning the use of azathioprine for AD, and have identified 128 cases in eight open studies, including our own prospective trial. Improvement in the majority was noted in seven studies, although objective measures of disease activity were used in only one trial. Measurements of TPMT activity were performed in the two most recent studies only. These data underscore the requirement for a prospective randomised controlled trial, and highlight the need to further investigate the role of TPMT measurement in azathioprine usage.

Topics: Azathioprine; Dermatitis, Atopic; Dermatologic Agents; Humans; Immunosuppressive Agents; Mercaptopurine; Methyltransferases; Prospective Studies; Treatment Outcome

Azathioprine is frequently used in severe eczema. It is converted in the liver into active metabolites, including 6-thioguanine nucleotide (6-TGN) and methylated 6-methylmercaptopurine (6-MMP). In the past, the therapeutic potential of azathioprine may have not been fully utilized. Recent investigations on inflammatory bowel disease have led to a better understanding of azathioprine metabolism and optimizing treatment.. To investigate whether measuring thiopurine metabolites in circulation can improve the effectiveness and safety of azathioprine treatment in patients with atopic dermatitis and/or chronic hand/foot eczema.. Azathioprine metabolite levels were measured in eczema patients during maintenance treatment (Part I) and dose escalation (Part II). Clinical effectiveness, hepatotoxicity, and bone marrow suppression were analyzed and TPMT genotype was assessed.. A wide variation in metabolite levels in all dose groups was observed. In Part I (32 patients), there were no significant differences in 6-TGN levels between clinical responders and non-responders (p = .806). No hepatoxicity or myelotoxicity was observed. In Part II, all 6-TGN and 6-MMP levels increased during dose escalation. Hypermethylation was observed in 2/8 patients.. For individual eczema patients treated with azathioprine, routinely measuring 6-TGN and 6-MMP can be helpful in optimizing azathioprine dose, improving clinical effectiveness, and preventing side effects.

Topics: Adult; Azathioprine; Chromatography, High Pressure Liquid; Dermatitis, Atopic; Eczema; Female; Guanine Nucleotides; Humans; Immunosuppressive Agents; Male; Mercaptopurine; Middle Aged; Thionucleotides; Treatment Outcome

Topics: Adult; Allopurinol; Azathioprine; Chronic Disease; Dermatitis, Atopic; Drug Therapy, Combination; Eczema; Female; Foot Dermatoses; Guanine Nucleotides; Hand Dermatoses; Humans; Immunosuppressive Agents; Male; Mercaptopurine; Middle Aged; Prospective Studies; Thionucleotides; Time Factors; Treatment Outcome

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.. 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.. 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.. 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.. Small sample size is a limitation.. 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.

Topics: Administration, Oral; Adolescent; Azathioprine; Child; Child, Preschool; Dermatitis, Atopic; Female; Guanine Nucleotides; Humans; Immunosuppressive Agents; Male; Mercaptopurine; Methyltransferases; Prospective Studies; Severity of Illness Index; Thionucleotides

Topics: Angioedema; Asthma; Depression, Chemical; Dermatitis, Atopic; Desensitization, Immunologic; Histamine H1 Antagonists; Humans; Hypersensitivity; Mercaptopurine; Pyrrolidines; Rhinitis, Allergic, Seasonal; Skin Tests; Urticaria; Xanthenes

Topics: Anemia; Anemia, Hemolytic; Dermatitis, Atopic; Dermatitis, Contact; Eczema; Humans; Lupus Erythematosus, Systemic; Mercaptopurine; Scleroderma, Systemic; Thioguanine