Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.67 (thiopurine methyltransferase)
 551 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Azathioprine has an important role in treatment of many inflammatory dermatoses. In view of the current emphasis on evidence-based medicine, we performed a questionnaire-based survey to establish current practice in the use of azathioprine by consultant dermatologists and associate specialists in the U.K. The response rate was 68%. In contrast with the manufacturer's recommendation, our data provide evidence that azathioprine is useful in the treatment of a wide variety of dermatological diseases. However, there is still a need for controlled trials in some conditions. The most common conditions treated were pemphigoid, pemphigus and atopic eczema. In addition, we found that only 13% of dermatologists prescribe azathioprine according to body weight. Most dermatologists felt that azathioprine was well tolerated. No one tested for thiopurine methyltransferase (TPMT) activity, which is thought to be a predictor of severe myelosuppression. The combination of prescribing azathioprine according to body weight and measuring TPMT activity would optimize efficacy and minimize potential severe myelotoxicity.
Br J Dermatol 1997 Mar
PMID:Azathioprine in dermatology: a survey of current practice in the U.K. 911 14

The treatment of autoimmune blistering diseases remains therapeutically challenging. Significant improvement in the management of autoimmune bullous diseases has occurred as a consequence of improvements in our ability to predict, monitor, and treat the deleterious effects associated with the drugs used to treat these conditions and the introduction of new agents with lower toxicity. Examples include improvements in monitoring and preventing osteoporosis in patients on long-term systemic corticosteroids, the detection of those at risk for azathioprine toxicity bowing to low thiopurine methyltransferase activity, and the addition of agents such as mycophenolate mofetil and IVIG to our therapeutic armamentarium. These advances offer the promise of improved disease control with fewer side-effects and long-term toxicity for our patients.
Dermatol Clin 1999 Apr
PMID:Treatment of autoimmune blistering diseases. 1032 7

The risk of azathioprine-induced myelosuppression can be predicted by detecting patients with intermediate or low thiopurine methyltransferase (TPMT) activity. Population studies have shown that 89% of whites have high TPMT activity, 11% have intermediate TPMT activity, and 0.3% have low TPMT activity. Three specific mutations in the TPMT gene that cause decreased TPMT activity have recently been identified. Patients homozygous for the TPMT mutations have low TPMT activity, and patients heterozygous for TPMT mutations have intermediate TPMT activity. This has led to the development of a technique for TPMT genotype analysis that will identify patients at risk of azathioprine-induced myelosuppression. We report a case of a patient with bullous pemphigoid who experienced azathioprine-induced myelosuppression and who was later found to be homozygous for TPMT mutant alleles. Using the cost of treatment required for this patient and the estimated population prevalence of TPMT mutations, we examined the cost impact of screening for TPMT mutations in all patients being considered for azathioprine therapy. We calculated that screening is cost-neutral assuming patients homozygous for TPMT mutations experience myelosuppression, and that it is cost-beneficial assuming patients heterozygous for TPMT mutations also experience myelosuppression while receiving azathioprine. Screening patients for TPMT mutations will reduce the risk of azathioprine-induced myelosuppression, and our study suggests that it may also be a cost-attractive strategy.
J Am Acad Dermatol 2000 Apr
PMID:Screening for azathioprine toxicity: a pharmacoeconomic analysis based on a target case. 1072 9

Azathioprine has been available as an immunosuppressive agent for over 40 years, and current routine usage in dermatology is not restricted to licensed indications. Advances in understanding the metabolic fate of azathioprine have led to significant changes in prescribing practice and toxicity monitoring by U.K. dermatologists. The current state of knowledge concerning the use of azathioprine in dermatology is summarized, with identification of strength of evidence. Clinical indications and contraindications for azathioprine usage in dermatology are identified. Evidence-based recommendations are made for routine safety monitoring of patients treated with azathioprine, including pretreatment assessment of red blood cell thiopurine methyltransferase activity.
Br J Dermatol 2004 Dec
PMID:Guidelines for prescribing azathioprine in dermatology. 1560 6

The study of pharmacogenetics will optimize the use of systemic therapies in dermatology. Directed prescription of azathioprine dependent on phenotypic expression of the thiopurine methyltransferase gene is now accepted practice. To some extent other, older drugs have been neglected. We look at the role that pharmacogenetics could play in the use of methotrexate for psoriasis, focusing on known polymorphisms in the folate metabolic pathway.
Br J Dermatol 2005 Nov
PMID:The potential of pharmacogenetics in optimizing the use of methotrexate for psoriasis. 1622 93

Azathioprine, a prodrug of 6-mercaptopurine, was developed over four decades ago. Since its development, azathioprine has been shown to have antileukemic, anti-inflammatory, and immunosuppressive properties. Hence, the reason azathioprine is used in multiple medical specialties. In the dermatology field, it is used as an immunosuppressant and corticosteroid-sparing agent for the treatment of several cutaneous diseases. In this article, the present authors review the following aspects relating to azathioprine: history, pharmacokinetics, significance of thiopurine methyltransferase, side effects, contraindications, therapeutic uses, and recommended evaluation and monitoring for patients initiating azathioprine.
Dermatol Ther
PMID:Azathioprine: a guide for the management of dermatology patients. 1797 Aug 86

Although there are no standard guidelines for the treatment of autoimmune blistering diseases, azathioprine has shown good efficacy in acquired autoimmune blistering diseases, and is well tolerated. Side effects of azathioprine normally occur in mild variants. Severe reactions are due to reduced thiopurine S-methyltransferase (TPMT) or inosine triphosphate pyrophosphohydrolase (ITPA) activity. Therefore, screening for TPMT activity should be conducted in white patients and Africans, whereas Japanese should be screened for ITPA activity before therapy with azathioprine is started. Azathioprine is clinically meaningful for the treatment of pemphigus.
Dermatol Clin 2011 Oct
PMID:Azathioprine in the treatment of autoimmune blistering diseases. 2192 96

Severe forms of atopic dermatitis (AD) cause significant morbidity in vulnerable pediatric populations and necessitate treatment with systemic therapy. The existing literature concerning the treatment of severe pediatric AD with azathioprine (AZ) and mycophenolate mofetil (MM) is sparse. The purpose of this case series is to examine the use of these two drugs in the treatment of severe pediatric AD. Medical records of 28 pediatric patients with AD from the University of North Carolina at Chapel Hill pediatric dermatology clinic treated using these two drugs were analyzed for laboratory values, thiopurine methyltransferase (TPMT) levels, symptoms, infections, and other relevant data. Patients were also contacted via the telephone to ascertain outcomes and any missing data. Treatment outcomes were scored into three categories: significant improvement, some improvement, and no improvement. AZ dosing was correlated to TPMT levels successfully, with comparable levels of improvement in the heterozygous and homozygous wild-type groups. Absolute eosinophil count corresponded to AD activity and treatment response across both treatment modalities in 18 of 26 (69%) patients. Seventeen of 28 (61%) patients treated with AZ and eight of 12 (66%) treated with MM reported significant improvement. We had lower rates of laboratory abnormalities and side effects with MM than with AZ but similar rates of cutaneous infections. Treatment outcomes did not appear to differ with race, sex, or TPMT level. We experienced success with AZ and MM in the treatment of severe pediatric AD. Coordinating treatment to each patient's unique morbidities is the best way to choose systemic treatments.
Pediatr Dermatol
PMID:Systemic treatment of pediatric atopic dermatitis with azathioprine and mycophenolate mofetil. 2196 57

Although azathioprine (AZA) combined with corticosteroids remains the first-line therapy to treat patients with pemphigus vulgaris (PV), there are increasing reports of AZA-induced leukopenia, which provides the rationale for monitoring the blood cell count and testing the genotypes at the thiopurine methyltransferase (TPMT) and the nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) genes. Here, we reported a case of persistent refractory PV in a Chinese patient with three runs of AZA-corticosteroids treatment. In the first two runs he received AZA-corticosteroids at standard or slightly reduced doses and developed leukopenia. In the third run of treatment, he was found to have NUDT15 mutation (rs116855232) and wild-type homozygous TPMT*3C (rs1142345), treatment with minimal doses of AZA and prednisone resulted in a complete remission of PV without any side effects including leukopenia. Our observations not only highlight the benefits of testing the TPMT and NUDT15 genotypes and monitoring the dynamic changes of the white blood cell count in guiding the AZA therapy, but also suggest the potential of using the AZA-corticosteroids combination at very low doses in the treatment of refractory PV.
Dermatol Ther 2020 Jul 26
PMID:Complete remission of refractory pemphigus vulgaris in a Chinese patient with mutated NUDT15 by combination of minimal doses of azathioprine and prednisone. 3271 39