methimazole and Psoriasis

We have previously reported that an antithyroid thiourethylene, thiamazole, can bring about significant clinical improvement in patients with psoriasis vulgaris. Although the efficacy of antithyroid thiourethylenes had been reported earlier, few studies have evaluated the safety of its long-term use. In this study, we aimed to study whether or not long-term thiamazole administration is complicated by any adverse effects. Eight patients with psoriasis vulgaris were enrolled in this study after informed consent was obtained. Each patient was administered thiamazole orally at 30 mg/day for 12 weeks. Two patients achieved complete clearance of psoriatic lesions. Four patients showed a significant improvement, and two patients did not reach satisfactory improvement. Some adverse effects developed in five patients; serum TSH levels elevated above the normal range in three patients and fell below the normal range in one patient. However, serum free-T3 and free-T4 levels remained within normal ranges during the treatment in all patients, and none of the patients developed clinical hypothyroidism. This preliminary study suggests that thiamazole administration is an effective and relatively safe treatment for patients with psoriasis vulgaris.

Topics: Administration, Oral; Adult; Antithyroid Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Long-Term Care; Male; Methimazole; Middle Aged; Prospective Studies; Psoriasis; Risk Assessment; Severity of Illness Index; Treatment Outcome

Methimazole, an antithyroid drug, was orally administered, in an open trial, in a dose of 20 mg every 12 h for 8 weeks to 8 volunteers with long-standing psoriasis. 3-mm punch biopsies were taken from the lesions at the start and at the end of the study. Clinical response was assessed using the Psoriasis Areas Severity Index score. Methimazole produced marked to moderate improvement in the clinical scores in the majority of patients. Histological scores were also significantly improved in all patients. Unexpectedly, thyroid function tests were not affected by methimazole therapy in all but one patient, and none of the patients developed drug-induced cytopenia. Methimazole may be an effective therapeutic agent in the management of psoriasis; it most probably exerts its therapeutic effect by acting on the immune system.

Topics: Adult; Female; Humans; Male; Methimazole; Middle Aged; Psoriasis; Skin

Psoriasis is a common skin disorder associated with significant morbidity. Many agents are used in the medical management of this debilitating condition with the newer anti-cytokine agents being the most recent addition to the pharmacological armamentarium to battle the disorder. Cost concerns are very important with the newer "biologic" treatments costing in excess of 10,000 US dollars annually. The need for cheaper, orally administered agents is therefore imperative. This paper addresses the potential role of anti-thyroid thioureylenes, propylthiouracil and methimazole, in the treatment of psoriasis and reviews the possible mechanism of action of these drugs in this disorder. It is hypothesized that the beneficial effect of anti-thyroid thioureylenes in psoriasis is linked to their effect as anti-proliferative agents as reflected by significant decrease in markers of cellular proliferation such as proliferative cell nuclear antigen in biopsy specimens after treatment with these drugs. Propylthiouracil has been shown to bind to the hepatic T 3 receptor and it is possible that propylthiouracil (6-n-propyl-2-thiouracil) binding to the ligand-binding site normally occupied by T 3 impairs transcription by inactivating the effect of T 3 as well as by squelching retinoic X receptor heterodimer formation with other receptors of the steroid receptor superfamily such as the peroxisome proliferator-activated receptor, retinoic acid receptor and vitamin D receptors.

Topics: Antithyroid Agents; Cytokines; Humans; Intercellular Adhesion Molecule-1; Methimazole; Propylthiouracil; Psoriasis

Antithyroid thioureylenes are effective agents in the oral and topical treatment of patients with chronic plaque psoriasis.. The effect of oral treatment with 6-n-propyl 2-thiouracil (propylthiouracil, PTU) and 2-mercapto 1-methyl imidazole (methimazole, MMI) on proliferating cell nuclear antigen (PCNA), and p53 protein expression was studied in patients with stable plaque psoriasis.. Following treatment with PTU and MMI, PCNA staining in psoriatic epidermis was significantly decreased. P53 was minimally expressed in untreated lesions, and treatment with PTU and MMI did not enhance p53 expression in the psoriatic lesions.. Since PCNA is a marker of cellular proliferation and p53 inhibits cellular cycling, some of the beneficial effects of PTU and MMI in psoriasis may depend on the ability of the drugs to impair cellular turnover, perhaps by binding to the triiodothyronine (T3) receptor. These effects may be in addition to the previously described effects of PTU and MMI as immune modulators and free radical scavengers.

Topics: Administration, Oral; Adult; Aged; Female; Gene Expression Regulation; Humans; Immunoenzyme Techniques; Male; Methimazole; Middle Aged; Proliferating Cell Nuclear Antigen; Propylthiouracil; Psoriasis; Tumor Suppressor Protein p53

Serum concentrations of intercellular adhesion molecule-1 (ICAM-1), a marker of early T-cell activation were measured in 14 patients with stable plaque psoriasis who received treatment for 8 weeks with the antithyroid thioureylenes, propylthiouracil (PTU) or methimazole (MMI) which have been previously shown to produce significant improvement in such patients. Baseline serum concentrations of ICAM-1 were significantly higher in the patients with psoriasis compared with normal control volunteers. Following therapy with either PTU (300 mg daily) or MMI (40 mg daily) serum ICAM-1 concentrations did not decline significantly. Since ICAM-1 expression on vascular endothelium increases in active psoriasis, and is postulated to promote T-cell migration to and retention at these sites, it is hypothesized that the beneficial therapeutic effects of thioureylenes in psoriasis occur distal to the events that lead to lymphocyte migration to vascular structures in the dermis.

Topics: Adult; Cell Adhesion Molecules; Humans; Intercellular Adhesion Molecule-1; Methimazole; Middle Aged; Propylthiouracil; Psoriasis

We have previously reported clinical improvement in patients with psoriasis who received orally administered antithyroid thioureylenes, propylthiouracil (PTU), and methimazole (MMI). The antithyroid drugs are believed to exert immunomodulatory effects based on the results of studies in patients with Graves' disease, the only disease in which they are clinically used. The potential of these drugs to mediate clinical improvement in patients with psoriasis by reducing expression of the interleukin-2 receptor (IL2R), a marker of early T and B cell activation, was addressed in the present study.. Baseline serum concentrations of IL2R were measured by an enzyme-linked immunosorbant assay (ELISA) in 15 patients with stable plaque psoriasis and in the same patients after 8 weeks of oral therapy with either 300 mg of propylthiouracil (n = 7) or 40 mg methimazole (n = 8) given daily. Baseline values were compared with normal controls.. Serum IL2R concentrations in the psoriatic patients were significantly higher than in normal controls. After treatment with PTU or MMI, IL2R serum concentrations were not significantly reduced either in the group as a whole or separately in the PTU and MMI treated patients.. Since elevated serum concentrations of IL2R often reflect T and B cell activation, and elevated IL2R serum levels are seen in several autoimmune diseases, it is speculated that the beneficial effect of thioureylenes in patients with psoriasis is mediated by some mechanism(s) other than reduction of IL2R expression in activated lymphocytes.

Topics: Adult; Female; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Psoriasis; Receptors, Interleukin-2

Topics: Adolescent; Adult; Chronic Disease; Diiodotyrosine; Drug Therapy, Combination; Female; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Psoriasis; Thyroid Function Tests; Thyroid Gland