Matthew M. Goodman

Propylthiouracil in psoriasis: Results of an open trial

BACKGROUND Propylthiouracil (PTU) is an antithyroid thioureylene that has immune modulatory and free radical scavenging abilities. In view of the immunomodulatory effects of PTU, we decided to study the therapeutic response of patients with psoriasis to oral PTU. OBJECTIVE Our purpose was to study the effect of oral PTU in patients with stable plaque psoriasis. METHODS Oral PTU, 100 mg, was administered every 8 hours for 8 weeks to 10 patients with long-standing psoriasis. Skin biopsy specimens were taken from the lesions before and at the end of the study. Clinical response was monitored with the Psoriasis Area and Severity Index scoring system. Histologic scores were graded with a 5-point grading scale. Complete blood cell count was obtained at the beginning and at the end of the study. Thyroid-stimulating hormone (TSH) was obtained at the beginning and every 2 weeks thereafter until completion of the study. RESULTS Three patients dropped out of the study. Of the remaining seven, two showed near-complete resolution of their psoriatic lesions, whereas the remainder showed moderate improvement in their clinical scores. Histologic scores were significantly improved in the group with all but one patient showing improvement or no change. Thyroid function tests were unchanged in all but one patient who showed a slight increase in serum TSH at the sixth week of therapy. CONCLUSION Because of its low toxicity relative to other oral treatments of psoriasis, PTU may have a role in the treatment of patients with this disorder.

Methimazole (2-Mercapto 1-Methyl Imidazole) in Psoriasis – Results of an Open Trial

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.

Multiple symmetric lipomatosis (Launois-Bensaude syndrome).

Two types of adipose tissue arc known to occur. White fat is the common adipose tissue found in the adult subcutaneous tissue, mediastinum, abdomen, and retroperitoneum. Brown fat is mainly found in the fetal neck, upper back, and retroperitoneum, and seldom persists beyond infancy. Proliferative disorders of the adipose tissue run a spectrum from benign to malignant and from small localized tumors to fairly widespread disorders. On one end of the spectrum are the lipomas: the most common mesenchymal neoplasms. Although they can occur in large numbers in certain patients, lipomas are generally few in number and localized. On the other end of the spectrum is multiple symmetric lipomatosis (MSL), an unusual widespread disfiguring disorder. A classic case of MSL and a review of the current understanding of this disorder are presented here.

Effect of propylthiouracil and methimazole on serum levels of interleukin-2 receptors in patients with psoriasis

Background. 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.

Serum ICAM‐1 concentrations in patients with psoriasis treated with antithyroid thioureylenes

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.

Cyclosporine therapy for psoriasis : a cell cycle-derived dosing schedule

BACKGROUND Cyclosporine is effective in the treatment of psoriasis; however, potentially serious side effects limit its long-term use. On the basis of the 36-hour psoriatic keratinocyte cell cycle, a new dosing regimen was investigated. OBJECTIVE The purpose of this study was to evaluate a 36-hour weekly dosing schedule with cyclosporine for the treatment of psoriasis, in an attempt to decrease side effects while maintaining efficacy. METHODS Fifteen patients were studied by means of oral doses of cyclosporine taken at 12-hour intervals for three doses per week during a 10-week period. The initial dose, 2.5 mg/kg/dose (7.5 mg/kg/wk), was increased every 2 weeks by 2.5 mg/kg/dose to a maximum of 10 mg/kg/dose. RESULTS The average improvement as assessed by the Psoriasis Area and Severity Index for all 15 patients was 61%. Six patients had a more than 75% improvement, three patients improved 50% to 74%, and six patients improved less than 50%. Three patients dropped out because of adverse side effects, and three others completed the study at a reduced dose. CONCLUSION It is concluded that, although effective, this dosing regimen may not have an advantage over daily dosing, given its side effect profile and the need to go to relatively high doses every 24 hours.