propylthiouracil and Psoriasis

Propylthiouracil (PTU) is an effective drug for psoriasis treatment. Prolactin (PRL) is increased during psoriasis which has hyperproliferative effect on keratinocytes. Hence, the objective is to find the effect of PTU on PRL level in psoriatic patients.. 25 psoriatic patients and 10 control subjects were involved in the study. Serum PRL, hematological and biochemical parameters, thyroid profile and histopathological examination were performed.. PTU treatment for 6 weeks and 12 weeks cleared psoriatic lesions indicated by decreased PASI score (p<0.001). Patients before treatment showed significantly increased PRL levels (male p<0.01, female p<0.001) when compared to controls, which was found to decrease significantly (male p<0.01, female p<0.001) after 12 weeks. Hematological and biochemical parameters showed no significant change. Histopathology showed reduced thickening of the epidermis and acanthosis after PTU treatment.. Since PRL is a growth hormone involved in hyperproliferation of keratinocytes, this study reveals the antiproliferative effect of PTU. Furthermore, no major side effects were observed following PTU treatment.

Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Prolactin; Propylthiouracil; Psoriasis; Treatment Outcome

Tumor necrosis factor-alpha (TNF-alpha) and its receptors play important roles in the development and persistence of psoriatic plaques. The antithyroid thioureylenes, propylthiouracil and methimazole, are effective in the treatment of patients with psoriasis with a significant number of patients showing clearing or near clearing of their lesions after a several weeks of treatment.. The present study examined the effect of treatment with propylthiouracil, given in a dose of 100 mg every 8 hours for 3 months, on the serum levels of TNF-alpha in 9 patients with plaque psoriasis.. Propylthiouracil therapy did not result in a significant decline in serum TNF-alpha concentrations.. The findings suggest that the therapeutic effect of propylthiouracil in psoriasis appears not to be related to any change in the concentration of TNF-alpha but occurs via an anti-proliferative mechanism as we have previously speculated.

Topics: Adult; Aged; Antimetabolites; Antithyroid Agents; Female; Humans; Male; Middle Aged; Propylthiouracil; Psoriasis; Tumor Necrosis Factor-alpha

There is growing evidence supporting the reactive oxygen species (ROS) in the pathogenesis of psoriasis. Propylthiouracil(PTU), an antithyroid drug, has been shown to have beneficial effects on psoriasis. The aim of this study was to investigate both disturbances in oxidant/antioxidant system in psoriasis and whether PTU, shown to have immunomodulatory effects and antioxidant potential, has effects on oxidant/antioxidant system and clinical improvement in psoriatics.. Malondialdehyde (MDA), end product of lipid peroxidation, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and antioxidant enzymes were measured in plasma, erythrocytes and skin biopsies of psoriatics who were resistant to conventional therapy before and after 8 weeks of oral treatment with PTU (300 mg/day) or PTU/thyroxine (25 microg/day- to prevent possible hypothyroidism). The same parameters were also studied in healthy controls. Psoriasis Area and Severity Index (PASI) scores were used to evaluate the severity of the disease, and routine analyses and thyroid function tests were measured during the study.. Increased baseline MDA in all samples were found to be lower. In addition baseline SOD and GSH-Px in skin and erythrocytes were also lower. The increased plasma SOD levels in skin and erythrocytes of the study groups was found to be higher and lower,respectively in all patients after the treatment. No tissue parameters or erythrocyte GSH-Px were different from control levels at the end of the study. Significant clinical improvement and decreased PASI scores were observed in all patients. Post treatment TSH levels were higher in all patients, but these levels were within the reference range and none had clinical hypothyroidism.. These findings may provide some evidence for a potential role of increased lipid peroxidation and decreased antioxidant activity in psoriasis. PTU may be considered as treatment model in psoriasis, in particular for resistant cases, because of its antioxidant potential, and also antiproliferative and immunomodulatory effects.

Topics: Adolescent; Adult; Aged; Antioxidants; Antithyroid Agents; Female; Glutathione Peroxidase; Humans; Male; Malondialdehyde; Middle Aged; Oxidants; Propylthiouracil; Psoriasis; Superoxide Dismutase; Thyroxine

T-cell activation has been implicated in the pathogenesis of psoriasis; adenosine deaminase (ADA) activity has been considered as a marker of T-cell activation. The antithyroid drug propylthiouracil (PTU) has recently been shown to have beneficial effects on psoriatic lesions, probably by acting on the immune system.. To investigate whether ADA activity may be related to psoriasis and whether oral PTU affects ADA activity and gives clinical improvement in psoriatic patients.. ADA activities were measured in plasma, erythrocyte and tissue samples of patients with psoriasis before and after 2 months of treatment with either PTU 100 mg three times daily or PTU plus thyroxine 25 microg once daily (to prevent possible hypothyroidism, which may be induced by PTU) as well as in healthy controls. The severity of the disease was evaluated before and after treatment according to Psoriasis Area and Severity Index (PASI) scores. Routine analyses and thyroid function tests were also carried out during the study.. All patients showed significant clinical improvement in their lesions and decreased PASI scores after the treatments. Elevated baseline ADA activities in skin and plasma were found to be lower, and decreased baseline erythrocyte ADA was higher, after the treatments in all patients, and they were not different from control values. Although thyroid function tests were not affected by the treatments, serum thyroid-stimulating hormone levels were found to be higher after the treatments, and there was a larger increase in patients treated with PTU alone. However, none of the patients had clinical hypothyroidism or cytopenia.. ADA activity may be clinically useful for indicating T-cell activation in psoriasis. Because of its antiproliferative and immunomodulatory effects, antioxidant potential and low toxicity, PTU may be an effective agent in the treatment of psoriasis.

Topics: Adenosine Deaminase; Adolescent; Adult; Aged; Biomarkers; Dermatologic Agents; Erythrocytes; Female; Humans; Hypothyroidism; Male; Middle Aged; Propylthiouracil; Psoriasis; Severity of Illness Index; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Propylthiouracil (PTU, 6-n-propyl 2-thiouracil) is an antithyroid thioureylene, which, in addition to its ability to decrease thyroid hormone synthesis, also has immune modulatory and free radical scavenging abilities. We have previously shown that oral PTU and another antithyroid thioureylene are effective in the treatment of plaque psoriasis.. The current study was performed to determine the efficacy of topical PTU in psoriasis.. Topical PTU and placebo were administered, in a double-blind fashion, three times daily for 4 to 8 weeks to nine volunteers with long-standing plaque psoriasis. The patients had biopsy specimens of their lesions taken at the start and end of the study. Clinical response was monitored with a scoring system based on scale, erythema, and thickness of the plaques. Complete blood cell count and thyroid function studies were obtained in each patient at the beginning and at 2-week intervals thereafter until completion of the study.. Topically applied PTU produced significant clearing of the lesions (clinical scores 8.0 +/- 0.6 vs 3.7 +/- 0.3, p < 0.0001 at 4 weeks, and 4.0 +/- 0.6, p < 0.02 at 8 weeks); two patients demonstrated nearly complete clearing. Placebo-treated and untreated "control" areas showed no significant change during the study. None of the subjects had hypothyroidism or cytopenia.. Topical applied PTU is effective in the treatment of patients with stable plaque psoriasis and has low toxicity.

Topics: Administration, Topical; Adult; Aged; Double-Blind Method; Female; Humans; Male; Middle Aged; Propylthiouracil; Psoriasis; Skin

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.. Our purpose was to study the effect of oral PTU in patients with stable plaque psoriasis.. 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.. 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.. 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.

Topics: Administration, Oral; Adult; Aged; Drug Tolerance; Epidermis; Female; Humans; Male; Middle Aged; Propylthiouracil; Psoriasis; Remission Induction; Thyrotropin; Time Factors

Propylthiouracil (PTU), an anti-thyroid thioureylene, has been shown to be effective in chronic plaque psoriasis. Involucrin is a precursor protein that is upregulated in psoriasis.. This study evaluated the expression of involucrin in the epidermis of skin in psoriatic plaques before and after treatment with PTU.. This was an open-label, prospective study in which 25 psoriasis patients underwent skin biopsies prior to treatment with oral PTU 100 mg three times per day for 12 weeks. Patients were assessed at 2, 6, and 12 weeks. Skin biopsies were repeated at the same sites at 12 weeks. Pre- and post-treatment specimens were subjected to immunohistochemical staining and real-time polymerase chain reaction for involucrin.. Mean ± standard deviation (SD) scores on the Psoriasis Area and Severity Index reduced significantly from 17.86 ± 9.9 at baseline to 4.63 ± 4.1 at week 12 (P < 0.001). Histomorphometric analysis revealed marked decreases in numbers of positively stained cells and intensity of staining. Staining became localized to the upper granular layers after therapy. Immunohistochemical scoring for involucrin reduced from a mean ± SD of 9.00 ± 0.67 at baseline to 3.90 ± 0.88 at week 12 (P < 0.0001).. In psoriasis, there is increased expression of involucrin, which leads to abnormal keratinocyte differentiation and hence to the formation of psoriatic plaques. The therapeutic effect of PTU in psoriasis may be attributable to the downregulation of involucrin. Larger trials should further elucidate the mechanism and therapeutic potential of PTU in psoriasis.

Topics: Adult; Aged; Antithyroid Agents; Down-Regulation; Female; Humans; Male; Middle Aged; Propylthiouracil; Prospective Studies; Protein Precursors; Psoriasis; RNA; Severity of Illness Index; Young Adult

Psoriasis greatly impacts the quality of life (QOL) of patients including several dermatological conditions that are listed in the Dermatology Life Quality Index (DLQI). Decrease in psoriatic lesion as measured by Psoriasis Area Severity Index (PASI) score is associated with improvement in QOL. Propylthiouracil (PTU) was found to be clinically efficient in clearing psoriatic lesions. Our objective is to find the extent of improvement in QOL in psoriatic patients treated with PTU.. Twenty-three psoriatic patients who were taking 300 mg PTU/day were involved in the study. Clinical improvement was assessed by PASI score and QOL was assessed by DLQI questionnaire at baseline, 6 th and 12 th week of PTU treatment.. Psoriatic patients before treatment showed significantly increased DLQI score when compared with 6 and 12 weeks of PTU treatment which was found to be decreased significantly (P < 0.001) after PTU treatment. There was a positive correlation between DLQI and PASI score at all three intervals of treatment period at P < 0.001 (r = 0.793, r = 0.834, r = 0.801), respectively.. Since PTU was found to improve the QOL of psoriasis patients, this study adds an advantage of using it as treatment option in psoriasis.

Topics: Adult; Antimetabolites; Female; Humans; Male; Patient Satisfaction; Propylthiouracil; Psoriasis; Quality of Life; Surveys and Questionnaires

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

Plaque formation is a characteristic finding in patients with psoriasis and reflects cytokine-induced keratinocyte proliferation and/or impaired apoptosis of keratinocytes. Antithyroid thioureylenes such as propylthiouracil (PTU) and methimazole (MMI) are effective in the treatment of plaque psoriasis. Following PTU and MMI treatment, proliferative cell nuclear antigen (PCNA) expression is significantly reduced, suggesting that these medications have an antiproliferative effect. p16 is an antiapoptotic protein that is present in relative abundance in psoriatic plaques and is believed to play a potential role in the persistent senescence and impaired apoptosis of the keratinocytes in the plaque. This study examined p16 expression in biopsy samples of eight patients with plaque psoriasis given 300 mg of propylthiouracil in divided doses for 3 months. Despite significant clinical and histological improvement with PTU treatment, p16 expression was essentially unchanged, suggesting that the beneficial effect of PTU in psoriasis is not mediated through a decrease in p16 expression. The effect of PTU on other antiapoptotic proteins such as bcl-xL remains to be determined.

Topics: Adult; Aged; Antimetabolites; Antithyroid Agents; Apoptosis; Biopsy; Cell Nucleus; Cyclin-Dependent Kinase Inhibitor p16; Female; Humans; Immunoenzyme Techniques; Keratinocytes; Male; Middle Aged; Propylthiouracil; Psoriasis; Remission Induction

The antithyroid thioureylenes, propylthiouracil (PTU) and methimazole (MMI), are effective in the treatment of patients with plaque psoriasis. The mechanism of action of the drugs in psoriasis is unknown. Since the drugs reduce circulating IL-12 levels in patients with Graves' hyperthyroidism, the effect of propylthiouracil on CD1a expression in psoriatic lesions was examined in biopsy samples of patients with plaque psoriasis. CD1a is a marker of differentiated skin antigen presenting cells (APC, Langerhans cells). Langerhans cells and skin monocyte/macrophages are the source of IL-12, a key cytokine involved in the events that lead to formation of the psoriatic plaque.. Biopsy specimens were obtained from six patients with plaque psoriasis who were treated with 300 mg propylthiouracil (PTU) daily for three months. Clinical response to PTU as assessed by PASI scores, histological changes after treatment, and CD1a expression in lesional skin before and after treatment were studied.. Despite significant improvement in clinical and histological parameters the expression of CD1a staining cells in the epidermis did not decline with propylthiouracil treatment.. It appears that the beneficial effect of propylthiouracil in psoriasis is mediated by mechanisms other than by depletion of skin antigen-presenting cells.

Topics: Adult; Antigens, CD1; Antithyroid Agents; Biopsy; Female; Humans; Male; Middle Aged; Propylthiouracil; Psoriasis

Propylthiouracil (PTU), an antithyroid thioureylene with immunomodulatory properties, has been shown to be effective in the therapy of patients with plaque psoriasis. The mechanism of action of antithyroid thioureylenes in psoriasis remains unknown. Propylthiouracil is a commonly used agent in the treatment of patients with Graves' hyperthyroidism, a condition associated with elevated levels of interleukin-12 (IL-12), which fall significantly after propylthiouracil treatment. IL-12 is believed to play a pivotal role in the development of psoriasis. Production of IL-12 is modulated by the anti-inflammatory cytokine IL-10. The effect of PTU on IL-12 and IL-10 levels was, therefore, studied in twelve patients with plaque psoriasis. Treatment with 300 mg of PTU daily in divided doses for three months produced significant improvement of the PASI and histological scores in the patients. Serum IL-12 concentrations were undetectable at baseline and did not change with treatment. IL-10 concentrations were 1.39 +/- 1.49 pg/ml (mean +/- SD) at baseline, and showed no significant change after 2 weeks (1.63 +/- 1.61 pg/ml and 12 weeks 1.15 +/- 1.58 pg/ml of treatment with PTU. The data suggest that the clinical improvement with patients with psoriasis treated with PTU is not due to a fall in circulating IL-12 or a rise in IL-10 concentrations. Although the drug may have effects on lesional production of these cytokines this is not reflected in the circulating levels. It is speculated that the beneficial effect is likely mediated by an inhibitory effect on keratinocyte proliferation or promotion of apoptosis in these proliferated keratinocytes.

Topics: Administration, Oral; Adult; Aged; Antithyroid Agents; Female; Humans; Interleukin-10; Interleukin-2; Male; Middle Aged; Propylthiouracil; Psoriasis; Treatment Outcome

Propylthiouracil (PTU) has been used in the treatment of hyperthyroidism for many years and inhibits the enzyme 5'-deiodinase, which converts thyroxine to triiodothyronine. Several studies have reported PTU as an effective treatment for plaque psoriasis. PTU exhibits immunomodulatory effects; however, its exact mechanism of action in psoriasis is unknown. Few patients were studied in these reports and treatment with PTU was continued for no longer than 8 weeks.. In this study we report on four patients with resistant plaque psoriasis who had treatment with oral PTU for 4-32 weeks (mean 18.4).. Three of the four patients exhibited moderate clinical improvement with reductions in psoriasis severity observed within 4-6 weeks of commencing PTU therapy. The side effects noted were subclinical hypothyroidism in two patients and worsening of muscle aches in one patient. Monitoring included regular thyroid function, full blood count, and liver and renal function tests.. This study illustrates that oral PTU can be a useful addition to the therapy of resistant cases of plaque psoriasis and shows that this treatment can be continued for longer than 8 weeks with few side effects occurring secondary to PTU.

Topics: Adjuvants, Immunologic; Administration, Oral; Adult; Aged; Female; Humans; Male; Middle Aged; Propylthiouracil; Psoriasis

A 71-year-old man with acrodermatitis continua of Hallopeau was treated successfully with a combination of oral propylthiouracil and methotrexate. After 14 weeks, he developed acute pancytopenia, an uncommon idiosyncratic side-effect of propylthiouracil, and presented with a life-threatening methicillin-resistant Staphylococcus aureus pneumonia. This illustrates the potential value and associated risks of propylthiouracil in the management of this difficult condition.

Topics: Acrodermatitis; Acute Disease; Aged; Antimetabolites; Drug Synergism; Drug Therapy, Combination; Humans; Kidney Failure, Chronic; Male; Methicillin Resistance; Methotrexate; Pancytopenia; Pneumonia, Staphylococcal; Propylthiouracil; Psoriasis; Staphylococcus aureus

Topics: Administration, Oral; Adult; Aged; Antithyroid Agents; Dose-Response Relationship, Drug; Humans; Male; Middle Aged; 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