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Indian Journal of Dermatology, Venereology and Leprology, Vol. 72, No. 3, May-June, 2006, pp. 234 Letter To Editor Parthenium dermatitis treated with azathioprine weekly pulse doses Srinivas CR Department of Dermatology, PSG Hospitals, Peelamedu, Coimbatore - 641 004,Tamil Nadu Code Number: dv06079 Related article: dv06080 Sir, We first reported the effectiveness of Azathioprine in the management of chronic actinic dermatitis induced by parthenium[1] and hence found the article titled parthenium dermatitis treated with azathioprine weekly pulse doses[2] very stimulating. As discussed in Wolverton's, Comprehensive Dermatologic Drug Therapy,[3] there are 3 pathways by which azathioprine's first metabolite (6MP) is metabolized. 1) It is anabolised to its active form, a purine analog, by the enzyme hypoxanthine-guanine phosphorvibosyl transferase (HGPRT), (2) Catabolised by thiopurine methyl transferase (TMPT) and by xanthium oxidase (XO) to inactive metabolites. The purine analog following anabolic pathway interferes with DNA & RNA synthesis. Both catabolic pathways lead to inactive metabolites. Reduced activity of either catabolic pathway have potentially dramatic effects clinically.[4] A large majority of patients (89%) show high levels of TPMT, intermediate levels of TPMT activity is seen in 11% and 1 in 300 patient have very low levels.[5] Patients with low TPMT have markedly increased levels of 6-thioguanine metabolites which increases the risk of pancytopenia.[3]On the other hand those with high levels of TPMT may catabolically inactivate more drug and low dose may not be effective.[5],[6] The recommendation of the authors[2] of using 300 mg weekly pulse needs to interpreted based on the of above facts. Although it is known that aggressive dosing with azathioprine may lead to more rapid clinical effect and this fact has been convincingly proved by the authors[2] what if a patient has low or very low TPMT. The authors recommend a test dose with 50 mg for 48 hours and then administering 300 mg of the drug. Since 11% of patients have only partial deficiency the tolerance of 50 mg does not mean that the patient can tolerate 300 mg. The story could have been different if the authors had studied at least 300 patients since very low levels are seen in 1 in 300 patients.[3] However the study can still be of practical use and I humbly suggest the following approach. The dose of azathioprine can be gradually built up to 150 mg or 200 mg daily over a period of 1 to 2 months and once the patient is able to tolerate this dose 300 mg may be safely administered at weekly intervals. Once TMPT assessment becomes routine, we can follow the authors'recommendation. References
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