thioguanine-anhydrous and Psoriasis

For patients with moderate to severe psoriasis, there is a large range of variably effective and safe oral, systemic medications. With appropriate monitoring, these therapies may be used as either monotherapy or in combination with other therapies. Newer drugs in the research pipeline hold significant promise.

Topics: Acitretin; Anti-Inflammatory Agents, Non-Steroidal; Antimetabolites; Cyclosporine; Fumarates; Humans; Hydroxyurea; Immunosuppressive Agents; Isoxazoles; Keratolytic Agents; Leflunomide; Methotrexate; Mycophenolic Acid; Piperidines; Protein Kinase Inhibitors; Psoriasis; Pyrimidines; Pyrroles; Sulfasalazine; Thalidomide; Thioguanine

Very few well designed studies have evaluated the conventional systemic agents for psoriasis. This is a systematic, evidence-based review of the literature evaluating both the efficacy and safety of the medications cyclosporine, methotrexate, acitretin, hydroxyurea, and 6-thioguanine. Treatment recommendations are made.

Topics: Acitretin; Clinical Trials as Topic; Cyclosporine; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Hydroxyurea; Immunosuppressive Agents; Methotrexate; Practice Guidelines as Topic; Psoriasis; Thioguanine; Treatment Outcome

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Arthritis, Rheumatoid; Azathioprine; Chlorambucil; Colitis, Ulcerative; Crohn Disease; Cyclophosphamide; Granulomatosis with Polyangiitis; Hepatitis; Humans; Immune Complex Diseases; Immunosuppressive Agents; Infections; Liver Cirrhosis, Biliary; Lupus Erythematosus, Systemic; Mercaptopurine; Methotrexate; Nephrotic Syndrome; Ophthalmia, Sympathetic; Psoriasis; Thioguanine; Uveitis

Patients with severe psoriasis may be unresponsive to or unable to tolerate the adverse effects of traditional therapy. Thioguanine has been used to treat psoriasis, but experience is limited. Most previous studies have used daily therapy and have demonstrated significant hematologic abnormalities.. To reduce the adverse effects of traditional thioguanine therapy, our study patients were treated with thioguanine with a pulse-dosing schedule of 2 to 3 times per week.. Marked improvement of recalcitrant psoriasis was noted in 10 (71%) of 14 patients receiving thioguanine therapy using a pulse-dosing schedule. Maintenance dosage ranged from 120 mg twice a week to 160 mg 3 times a week. Adverse effects were minimal.. Thioguanine therapy is an effective treatment for recalcitrant psoriasis. A dosing schedule of 2 or 3 times per week is recommended to minimize the potential adverse effects. Routine laboratory follow-up is suggested to screen for potential adverse effects, with special attention to bone marrow suppression.

Topics: Adult; Aged; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Psoriasis; Severity of Illness Index; Thioguanine

A recently described method that enumerates variant 6-thioguanine resistant peripheral blood lymphocytes present in vivo in man as a potential marker of somatic cell mutations occurring in vivo was used to study 18 psoriatic patients receiving PUVA therapy, 16 conventinally treated psoriatic patients, 10 vitiligo patients receiving PUVA therapy and 7 untreated individuals with vitiligo. Variant lymphocyte frequencies determined for these individuals were compared with those determined for groups of 10 concurrent and 63 cumulative healthy control individuals. Variant frequencies were elevated in psoriatic and vitiligo patients receiving PUVA therapy and in conventionally-treated psoriatic patients. They were not elevated over control values in untreated vitiligo patients.

Topics: Adult; Clinical Trials as Topic; Female; Humans; Lymphocytes; Male; Methoxsalen; Middle Aged; Mutation; Photochemotherapy; Psoriasis; Thioguanine; Ultraviolet Rays; Vitiligo

Topics: Biopsy, Needle; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Hepatic Veno-Occlusive Disease; Humans; Liver Function Tests; Middle Aged; Psoriasis; Risk Assessment; Severity of Illness Index; Thioguanine

A variety of systemically administered drugs are used to treat psoriasis, including methotrexate, cyclosporine, acitretin, and hydroxyurea. Unfortunately, some patients are unresponsive to these agents. For others, side effects and cumulative toxicity prevent continued use.. Our purpose is to report the results of thioguanine (6-thioguanine) treatment of 21 patients with refractory psoriasis.. We conducted a retrospective review of the treatment courses of 21 patients with psoriasis who were treated with thioguanine. Daily dosing and pulse dosing were both used, from 20 mg two times a week to 120 mg daily. All patients had been treated with other systemic therapies, and the majority (86%) had been treated with methotrexate.. Patient outcome (response to treatment relative to baseline) was classified into 3 groups: those with more than 90% improvement, those with between 50% and 90% improvement, and those with less than 50% improvement. Outcome data were based on the patient's subjective rating of disease severity before the start of thioguanine therapy and during the entire treatment course. Of the 18 patients able to be evaluated, 14 of 18 (78%) had dramatic improvement (>90%); 3 of 18 (17%) had lesser improvement (50%-90%); and only 1 of 18 had less than 50% improvement. The mean duration of treatment was 15.5 months. The primary side effect was myelosuppression, mild in 9 of 18 (white blood cell counts ranging from 1600-3700/microL; platelet counts ranging from 90,000-122,000/microL, and hematocrit values ranging from 24%-31%), and severe in 1 of 18 (white blood cell count of 1300/microL, platelet count of 17,000/microL, and hematocrit of 20%).. Thioguanine appears to be an effective treatment for patients with severe recalcitrant psoriasis. Myelosuppression is a significant, but easily monitored side effect that can now be more accurately predicted by determining thiopurine methyltransferase levels before starting thioguanine. Further prospective studies are needed to establish criteria, which will maximize efficacy of this drug in the treatment of psoriasis and minimize toxicity.

Topics: Adult; Aged; Aged, 80 and over; Bone Marrow; Digestive System; Drug Evaluation; Female; Humans; Male; Middle Aged; Psoriasis; Retrospective Studies; Thioguanine; Treatment Outcome

Psoriasis is a common and persistent disease characterized chiefly by marked epidermal and endothelial cell proliferation and inflammation. These changes are likely a result of activated T lymphocytes infiltrating skin tissue or, in the case of psoriatic arthritis, the joints.. To test the hypothesis that the antimetabolite 6-thioguanine (Sigma-Aldrich, St Louis, Mo) might be an effective treatment for psoriasis vulgaris because of its antilymphocytic effects.. Twenty patients with moderate to severe plaque-type psoriasis were treated with 6-thioguanine for 6 months. The clinical disease was assessed by the psoriasis severity index. Biopsy specimens obtained from lesional skin before treatment and after 1 and 2 months of treatment were examined for disease-related abnormalities using histochemical and computer-assisted image analysis. Antiproliferative effects of 6-thioguanine were compared in human keratinocytes and mitogen-activated lymphocytes over a range of drug concentrations, while viability, cell-cycle, and DNA fragmentation analysis were done using flow cytometry-based assays.. After 6 months of treatment, disease severity in 18 of 20 patients showed a significant response to 6-thioguanine: 12 patients were completely cleared of trace disease; 6 showed marked clinical improvement; and 2 did not respond. Patients showed reductions in peripheral blood lymphocytes and total leukocytes, but therapeutic response correlated best with cutaneous T-cell depletion. In vitro assays established that 6-thioguanine has major cytotoxic effects (apparently S-phase specific) on activated T lymphocytes via the induction of apoptosis. Keratinocytes and unactivated T cells, on the other hand, were largely unaffected by incubation with 6-thioguanine.. 6-Thioguanine is effective for the treatment of moderate to severe plaque-type psoriasis, and may be safe when given for defined periods and with careful hematologic monitoring. The mechanism of action of this drug seems to be the induction of apoptosis in activated T lymphocytes.

Topics: Administration, Topical; Adult; Antimetabolites, Antineoplastic; Apoptosis; Cell Division; DNA Fragmentation; Dose-Response Relationship, Drug; Female; Flow Cytometry; Humans; Keratinocytes; Lymphocyte Activation; Male; Psoriasis; T-Lymphocytes; Thioguanine

Despite recent innovations a considerable number of patients with psoriasis cannot be successfully treated by current therapies.. Our purpose was to summarize our 18-year experience with the antimetabolite 6-thioguanine in the management of patients with psoriasis.. We retrospectively studied 81 patients who were treated with 6-thioguanine. A variety of schedules were used to find the optimal schedule. Forty-eight percent of the patients either had been treated with methotrexate or were excluded from receiving methotrexate because of liver or kidney disease.. Forty-nine percent of patients with plaques were effectively maintained with 6-thioguanine for a median of 33 months. Four of five patients with palmoplantar pustular psoriasis experienced substantial benefit. The most common side effect was myelosuppression.. 6-Thioguanine is an effective therapy for psoriasis and should be considered for patients who have failed to respond to other systemic agents.

Topics: Adult; Aged; Aged, 80 and over; Bone Marrow; Digestive System; Female; Humans; Liver; Male; Middle Aged; Psoriasis; Retrospective Studies; Thioguanine

Topics: Adult; Hepatic Veno-Occlusive Disease; Humans; Liver Function Tests; Male; Psoriasis; Thioguanine

Topics: Biopsy; Drug Administration Schedule; Drug Resistance; Female; Follow-Up Studies; Humans; Liver; Male; Methotrexate; Middle Aged; Psoriasis; Thioguanine

The efficacy of thioguanine in the treatment of severe cases of psoriasis is demonstrated. This treatment is valuable in selected cases of severe psoriasis in whom other treatment is ineffective or impossible due to side effects. The effect of thioguanine on psoriasis lesions appears to run parallel with depression of the bone marrow. The bone marrow toxicity has to be considered. Patients previously treated with methotrexate are very sensitive to thioguanine and close follow up is mandatory with adjustment of the thioguanine dose according to blood white cell and thrombocyte levels.

Topics: Bone Marrow Diseases; Humans; Psoriasis; Thioguanine

Topics: Allergens; Allergy and Immunology; Aniline Compounds; Antibody Formation; Antigen-Antibody Reactions; Antineoplastic Agents; Azathioprine; Benzene; Catechols; Geriatrics; Humans; Hypersensitivity, Delayed; Immunocompetence; Immunosuppressive Agents; Mercaptopurine; Methotrexate; Pharmacology; Plague Vaccine; Psoriasis; Thioguanine; Triethylenemelamine; Vinblastine

Topics: Antineoplastic Agents; Autoimmune Diseases; Dermatitis; Dermatitis, Atopic; Dermatomyositis; Drug Therapy; Genetics, Medical; Humans; Lupus Erythematosus, Systemic; Neurodermatitis; Psoriasis; Scleroderma, Systemic; Thioguanine; Vascular Diseases