mercaptopurine and Eczema

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 employed for its immunosuppressive properties, as a steroid-sparing agent or as monotherapy. Its most traditional clinical indications are connective tissue diseases, vasculitis, post-transplant, and immunobullous dermatoses. The main disadvantages of azathioprine therapy are a delayed onset of action (6-8 weeks), and rare profound bone marrow toxicity. Susceptibility to bone marrow toxicity is due to a genetically determined metabolic defect (1 in 300). Patients at risk of such toxicity may be identified by a Thiopurine methyltransferase enzyme assay. We have undertaken a retrospective study, looking at the use of azathioprine as monotherapy for non-bullous inflammatory dermatoses. We studied a total of 24 patients (10 male, 14 female). The dermatoses comprised: atopic eczema (10), pompholyx (6), plaque psoriasis (6), and chronic actinic dermatitis (2). All patients had severe refractory disease warranting systemic second line therapy. The mean age was 49.4 years (range 17-86 years). The starting dose of azathioprine was 100-150 mg/day, and the maintenance dose 50-100 mg/day. The mean duration of treatment was 33.5 months(range 1-132 months). Eighteen patients (75%) showed a good to excellent sustained clinical response to azathioprine. This response rate was evenly represented in the 4 dermatoses studied. The adverse reactions encountered were raised MCV (6), leucopenia (2), raised hepatic enzymes (6), and dyspepsia (4). Azathioprine had to be discontinued due to adverse reactions in 2 patients (dyspepsia, raised hepatic enzymes) followed by normalization. Other factors that potentially contributed to the observed adverse events were present in 5 patients: alcoholism (2), erythromycin toxicity (1), and malabsorption (2). Our study demonstrates the efficacy of azathioprine monotherapy for severe atopic eczema, pompholyx, plaque psoriasis, and chronic actinic dermatitis. Furthermore, azathioprine is a low cost and generally well tolerated drug.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Azathioprine; Eczema; Eczema, Dyshidrotic; Female; Humans; Immunosuppressive Agents; Male; Mercaptopurine; Middle Aged; Retrospective Studies; Skin Diseases

Topics: Adult; Antibody Formation; Desensitization, Immunologic; Dimethyl Sulfoxide; Eczema; Female; Humans; Male; Mercaptopurine; Middle Aged; Solutions

Topics: Azathioprine; Dermatitis, Exfoliative; Eczema; Glucocorticoids; Humans; Male; Mercaptopurine; Middle Aged

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