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PubMed2004

[Treatment of scalp psoriasis. An effective and safe tacalcitol emulsion].

BACKGROUND: The scalp is a problematic area in psoriasis where treatment is often difficult. The lesions often extend beyond the hairline to involve the forehead, neck and sensitive facial skin. Topical corticosteroids and potentially irritant topical preparations have only limited utility in these sensitive areas. Most of the patients additionally suffer from psychosocial problems due to the visibility of lesions. OBJECTIVE: The aim of this multicenter, prospective, randomized, double-blind study, was to assess efficacy, safety and tolerability of once daily tacalcitol emulsion (4 micro g/g) compared to placebo in the treatment of scalp psoriasis. METHODS: To determine efficacy, safety and tolerability, 273 patients with mild to moderate scalp psoriasis were treated over a 8-week period. Response to treatment was evaluated using the sum score of erythema, infiltration and scaling. Global improvement of psoriasis was rated by the investigators and the patients using a 5-point scale. In addition the single scores of erythema, infiltration and scaling were assessed by the investigators, and the patients were asked to evaluate the intensity of itching and scaling over the treatment period. RESULTS: Tacalcitol was significantly superior to placebo in reducing the severity of scalp psoriasis. At the end of the study, the median sum score decreased by 53% in the tacalcitol group and was significantly better than placebo with 30% (p<0.0001). Global assessment of improvement was significantly greater in the tacalcitol group in both investigator and patient evaluation. 80% of patients on tacalcitol showed improvement to clearance and was statistically significant better than placebo (p <0.0001) in the investigator rating after 8 weeks. Tacalcitol was significantly superior to placebo in reducing erythema, scaling and infiltration, and in the patient assessment in reducing scalp scaling and itching. Treatment was very well tolerated. Local reactions were transient and uncommon. Their incidence was similar in both treatment groups. No serious side effects were reported, including those relating to calcium homeostasis or vitamin D(3) metabolism. No changes in mean levels of serum calcium, parathyroid hormone (PTH), calcitriol and in 24h-urinary excretion were observed. CONCLUSION: The results of this study indicate that topical application of tacalcitol (4 micro g/g) emulsion once daily is an effective, safe and very well- tolerated treatment for scalp psoriasis.

Adolescent↗
PubMed2005

[Psychosocial consequences of psoriasis--an empirical study of disease burden in 3753 affected people].

BACKGROUND AND OBJECTIVE: The aim of this study was to determine the psychosocial consequences of psoriasis in a large sample in Germany. PATIENTS AND METHODS: A questionnaire including the Psoriasis Disability Index (PDI) circulated by the German Psoriasis Alliance was answered by 3753 members representing a return rate of 42.3%. Psoriasis was graded-at the time of the examination-with less than 3% of the body surface affected as "mild", between 3 and 10% as "moderate," and more than 10% as "severe." RESULTS: The general impact of the illness on everyday life was "mild" in about 27%, "problematic" in about 45%, and "severe" in about 25% of the respondents. About 50% of the participants in the study had, concerning the skin, "mild" (PDI=9), about 35% "moderate" (PDI=14), and about 15% "severe" psoriasis (PDI=19). The differences of the PDI values are significant (ANOVA: p<0.001). CONCLUSIONS: This investigation confirms the enormous burden caused by the skin disease in the form of impairment and stigmatization, depending on the somatic severity, even when the current affection is rather mild. In connection with psychosocial consequences, future study should also focus on the disease burden of psoriasis.

Cost of Illness↗
PubMed2002

Analysis of phenotypic variation in psoriasis as a function of age at onset and family history.

To evaluate the relationship between psoriasis disease severity, age at onset, and family history, we analyzed 537 US psoriatics, most of whom were from Michigan. Total body surface area involvement (%TBSA), presence or absence of joint complaints, and nail involvement were measured. Analysis of familial psoriatics revealed that %TBSA was 15.1% when onset was early, but only 8.7% when onset was late ( P=0.00003). The opposite trend was seen when psoriasis was sporadic: %TBSA was 14.3% when onset was early (</=40 years of age) compared to 28.0% when onset was late ( P=0.0034). However, the sporadic group was small and ascertainment of the sporadic group was biased for severe involvement. As determined by log-linear analysis, joint complaints and age at onset were not significantly associated after controlling for age at examination, nor were joint complaints and familial status. Psoriatic nail changes were conditionally independent of familial status, given age at onset; nail changes were more frequently encountered in early-onset patients. There was no significant difference in the frequency of carriage of the MHC psoriasis risk determinant in the familial vs sporadic groups. Early-onset psoriatics did carry this determinant significantly more frequently, as expected. These results demonstrate increased severity of skin and nail disease in early-onset psoriasis, when psoriasis is familial. The lack of clinical differences between "familial" and "sporadic" psoriasis may reflect a similar genetic basis for both conditions, at least when onset is early.

Adolescent↗
PubMed2003

Polymorphisms of tumor necrosis factor (TNF) alpha and beta genes in Korean patients with psoriasis.

To evaluate the association of TNF-alpha (TNFA) and TNF-beta (TNFB) polymorphisms with psoriasis in the Korean population, we investigated TNF-alpha -238 and -308 promoter region and TNF-beta NcoI polymorphism using PCR-RFLP in 103 Korean psoriasis patients and 125 normal controls. The carriage and allele frequencies of TNFB*2 were significantly increased in patients with psoriasis compared with normal controls. However, TNFB*1/1 homozygote and TNFB*1 allele were significantly decreased in the patients. There were no significant differences in the polymorphism of TNF-alpha promoter -238 and -308 between the patients and controls. We also analyzed the frequencies of TNFB alleles according to the clinical characteristics of the psoriasis patients, but no significant differences were found. However, female patients with early-onset psoriasis showed an association with the TNFB*2 allele. In conclusion, our results suggest that polymorphisms of the TNFB gene may contribute to a predisposition to psoriasis in the Korean population.

Adolescent↗
PubMedDate not supplied

Hyporesponsiveness of peripheral blood lymphocytes to streptococcal superantigens in patients with guttate psoriasis: evidence for systemic stimulation of T cells with superantigens released from focally infecting Streptococcus pyogenes.

Throat infection with Streptococcus pyogenes is the most important trigger for acute guttate psoriasis. We examined the in vitro responses of peripheral blood mononuclear cells (PBMC) to streptococcal superantigens, SPEA and SPEC, and staphylococcal superantigens, SEB and TSST-1, in patients with guttate psoriasis, in patients with chronic plaque psoriasis, and in healthy subjects. PBMC from patients with guttate psoriasis responded poorly to SPEA and SPEC at concentrations of 0.1 and 1 ng/ml as compared with those from patients with plaque psoriasis, but showed high responses to SEB and TSST-1. The hyporesponsiveness recovered after improvement of the skin eruption. There was no significant difference between guttate and chronic types of psoriasis in the percentage of circulating T-cell receptor BV2 or BV8-bearing T cells, responsive to streptococcal superantigens, indicating that T-cell clonal anergy was a mechanism underlying the hyporesponsiveness. Our results suggest that superantigens released from focally infecting S. pyogenes induce a transient activation of relevant T cells, leading to the development of skin eruption and, subsequently, temporary T-cell anergy to these toxins.

Adult↗
PubMedDate not supplied

Mycophenolate mofetil (CellCept) for psoriasis: a two-center, prospective, open-label clinical trial.

BACKGROUND: Mycophenolate mofetil (MMF) is an immune suppressant that selectively inhibits activated lymphocytes. Its usefulness in treating psoriasis has not been systematically investigated. OBJECTIVE: To evaluate efficacy and safety of MMF as a monotherapy for psoriasis. METHODS: This is a two-center, prospective, open-label clinical trial. RESULTS: Twenty-three patients with moderate to severe psoriasis [mean psoriasis area and severity index (PASI) of 21.7] were treated with MMF 2-3 g/day for 12 weeks. Eighteen patients completed the study. The PASI was reduced by 24% (p < 0.001) at 6 weeks, and by 47% (p < 0.001) at 12 weeks. At the end of the treatment phase, 77% of the patients had significant reduction of PASI while 22% did not respond. The treatment was well tolerated. Five patients experienced mild nausea. One patient each had periorbital edema and pruritus. One patient had transient leukopenia. CONCLUSION: In this noncontrolled trial, the majority of patients with moderate to severe psoriasis responded to mycophenolate mofetil monotherapy with few adverse events. A randomized, controlled trial should be considered to confirm the usefulness of MMF as a monotherapy for psoriasis.

Adult↗
PubMedDate not supplied

The frequent use of oral retinoids in combination with other treatments for psoriasis: a retrospective analysis.

BACKGROUND: Combination treatment in psoriasis may be common, logical, and appropriate, even if not well tested or well documented by clinical trials. While oral retinoids such as acitretin can be used as monotherapy, efficacy can be further augmented by combination use with other agents. Similarly, because of its safety profile, acitretin can be added in low doses to help patients who have not achieved adequate control with other psoriasis treatments. OBJECTIVE: The purpose of this study was to assess how oral retinoids are used in combination with other drugs to treat psoriasis. METHODS: We assessed the use of acitretin and other oral retinoids for the treatment of psoriasis using two sources of information: nationally representative survey data from the National Ambulatory Medical Care Survey (NAMCS) and local data obtained by chart review of 518 patients seen in a university dermatology clinic. RESULTS: In the NAMCS, oral retinoids were prescribed with other psoriasis medications at 71% of visits. In the chart review, combination use was even more frequent (96% of subjects were on combination treatment) and included combinations of acitretin with topicals, phototherapy, and other systemic treatments. Adverse events were reported in 53% of patients treated with acitretin, although none were severe. CONCLUSION: Use of acitretin in combination with many other psoriasis treatments is a common practice. Mucocutaneous side effects of oral retinoids are common but with appropriate dosing are generally mild.

Acitretin↗
PubMed2005

Safety and efficacy of a milk-derived extract in the treatment of plaque psoriasis: an open-label study.

BACKGROUND: XP-828L is a nutraceutical compound obtained by the extraction of a growth factors-enriched protein fraction from bovine milk. XP-828L may improve psoriasis. OBJECTIVES: An open-label study was performed to determine the efficacy, tolerability and safety of XP-828L in the treatment of plaque psoriasis. METHODS: Eleven adult patients with chronic, stable plaque psoriasis on 2% or more of body surface area (BSA) received 5 g of oral XP-828L twice daily for 56 days. RESULTS: All 11 patients completed the 56 days of treatment. At day 28, 6 of the 11 patients showed a reduction in PASI score. At 56 days, seven subjects had a decrease in PASI score ranging from 9.5% to 81.3%. Eight (8) out of 11 patients agreed to participate in an additional 8-week extension treatment phase. Improvement of psoriasis was maintained during the extension period. No clinically significant adverse events or laboratory abnormalities occurred. CONCLUSION: XP-828L may improve psoriasis in patients with mild-to-moderate psoriasis.

Administration, Oral↗
PubMed2005

Pharmacokinetic-pharmacodynamic-efficacy analysis of efalizumab in patients with moderate to severe psoriasis.

PURPOSE: Efalizumab is a humanized anti-CD11a monoclonal antibody that demonstrated efficacy in the treatment of patients with psoriasis. The objective of this study was to perform a pharmacokinetic (PK)-pharmacodynamic (PD)-efficacy (E) modeling analysis with intersubject variability assessment to increase our understanding of the interaction of efalizumab with CD11a on T cells and consequent reduction in severity of disease in psoriasis patients. METHODS: A total of 6,329 samples from 240 patients in five Phase I and II clinical studies were used in the analysis. For the analysis, plasma efalizumab concentration was used as the PK measurement, the percent of predose CD11a was used as the PD measurement, and the psoriasis area and severity index was used as the measure of efficacy. A receptor-mediated PK/PD model was developed that describes the dynamic interaction of efalizumab binding with CD11a. In the efficacy model, the rate of psoriasis skin production is directly proportional to the amount of free surface CD11a on T cells, which is offset by the rate of skin healing. An additional CD11a-independent component to psoriasis skin production accounted for incomplete response to efalizumab therapy. A Monte Carlo parametric expectation maximization method implemented in the ADAPT II program was used to obtain the estimate of population parameters and inter- and intrasubject variability. RESULTS AND CONCLUSIONS: The final model described the PK/PD/E data in psoriasis patients reasonably well. In addition, simulations using the final model suggested that efalizumab administered less frequently could possibly be more convenient with similar efficacy.

Adult↗
PubMed1985

Serum angiotensin converting enzyme activity in patients with psoriasis.

Serum angiotensin converting enzyme activity is frequently increased in patients with active sarcoidosis. In spite of a reported association between sarcoidosis and psoriasis, serum angiotensin converting enzyme activities have not been reported for patients with psoriasis. We found the mean (SD) angiotensin-converting enzyme activity for 51 healthy subjects was 18.6 (5.8) kU/l, but for 52 patients with psoriasis without coexisting sarcoidosis, it was 28.3 (6.7) kU/l. There is a significant difference between these means (p less than 0.01). Forty-two percent (22/52) of the psoriasis patients had an increased serum angiotensin converting activity. Other diseases sometimes associated with an increased serum angiotensin converting enzyme activity were excluded as possible causes of a elevated activity in our patients with psoriasis. We conclude that almost half of the patients with psoriasis will have an elevated serum angiotensin converting enzyme activity, even when coexisting sarcoidosis is absent.

Humans↗
PubMed1990

A double-blind vehicle-controlled study of R 68 151 in psoriasis: a topical 5-lipoxygenase inhibitor.

Recently the pharmacologic role of leukotrienes (LTs), especially that of LTB4, has been intensively investigated in psoriasis. In vitro, R 68 151 is a potent 5-lipoxygenase inhibitor and consequently reduces LTB4 formation. Therefore the role of an in vitro 5-lipoxygenase inhibitor and its clinical use in psoriasis were evaluated with topical R 68 151 in a double-blind vehicle-controlled study. Eighty-eight patients with localized psoriatic lesions were treated twice daily with R 68 151 2% ointment (n = 44) or vehicle ointment (n = 44) during 4 weeks. Most patients (n = 73) had psoriasis vulgaris (n = 37, R 68 151; n = 36, vehicle). In 27% of the R 68 151-treated patients with psoriasis vulgaris, the lesions disappeared or showed marked improvement, compared with 8% in the vehicle group (X2, p = 0.06). The scores in global evaluation, however, were significantly different between both treatment groups (p less than 0.05, Mann-Whitney U test). The improvement of the mean symptom score with R 68 151 was 46% for scaling and 34% for erythema at the end of the study compared with an improvement of 6% and a deterioration of 3%, respectively, in the control group (p less than 0.05, p less than 0.01; Mann-Whitney U test). The global evaluation in the total group of patients with psoriasis (all different subtypes) was consistent with the response rate in the group of patients with psoriasis vulgaris: 30% in the test group versus 11% in the control group (X2, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1993

Alcohol intake and treatment responsiveness of psoriasis: a prospective study.

BACKGROUND: Alcohol has been reported to be a risk factor in psoriasis mainly based on the observation that there is a higher prevalence of alcohol abuse in persons with psoriasis, especially in men. OBJECTIVE: We prospectively examined the relation between pretreatment average daily ethanol consumption and treatment outcome in inpatients with moderate to severe psoriasis. METHODS: The severity of psoriasis of 94 inpatients (48 men and 46 women) was assessed before and after treatment. Ethanol use was determined by obtaining the patients' reports of their average daily consumption of alcoholic beverages during the 6 months before admission. RESULTS: The average daily ethanol intake of more than 80 gm before treatment was more frequently associated with less treatment-induced improvement (less than 10%) (p = 0.02) in the percentage of the total body surface area affected by psoriasis in men but not in women. CONCLUSION: Ethanol abuse may have an adverse effect on treatment outcome in men with psoriasis.

Adult↗
PubMed1995

Prolonged occlusion in the treatment of psoriasis: a clinical and immunohistologic study.

BACKGROUND: An occlusive dressing that is both cosmetically acceptable and long term is needed for psoriasis treatment. The mechanisms that underlie the efficacy of occlusion in psoriasis are unknown. OBJECTIVE: We performed a clinical and immunohistologic study in patients with psoriasis of the effects of occlusion, topical corticosteroid alone, and occlusion plus corticosteroid, with a new prolonged dressing as the occlusive therapy. METHODS: Nineteen patients completed a 3-week study of efficacy of prolonged occlusion dressing, fluocinonide ointment, or a combination of the two. An immunohistologic study was performed in 10 patients with psoriasis treated for 1 week with prolonged occlusion. RESULTS: The combination of fluocinonide ointment and occlusion produced significantly more improvement than either treatment alone (p < 0.01). There was no significant difference between the efficacy of prolonged occlusion or fluocinonide ointment. On 4-week follow-up plaques treated with occlusion alone or combined fluocinonide and occlusion were still significantly improved (p = 0.05 and p < 0.001, respectively). None of the immunohistologic and proliferation markers assessed in psoriatic plaques was significantly affected by occlusion as compared with untreated plaques. CONCLUSION: Prolonged occlusion is an effective therapy for psoriasis either as monotherapy or in combination with a high-potency topical corticosteroid. However, the mechanism of action of prolonged occlusion alone in the improvement of psoriasis is unknown.

Administration, Cutaneous↗
PubMed1995

Zidovudine for the treatment of HIV-negative patients with psoriasis: a pilot study.

BACKGROUND: Zidovudine, an inhibitor of HIV replication, has been reported to improve psoriasis in HIV-positive patients. OBJECTIVE: Our purpose was to evaluate the safety, tolerance, and effectiveness of oral zidovudine for treating psoriasis in HIV-negative patients in a small, open-label study. METHODS: Each subject received 200 mg of zidovudine every 4 hours during waking hours, for a total of 1000 mg/day. Treatment was continued for 8 weeks, at which time the patient's response to therapy was evaluated. If a response was evident, treatment was continued for an additional 8 weeks. Clinical response was correlated with histologic changes in skin lesions at 0 and 4 weeks. RESULTS: Thirty-three percent of HIV-negative patients with psoriasis showed improvement by up to 80% after 16 weeks of therapy; decreased elevation and scaling of the psoriasis plaques were the most notable changes. No complete remissions occurred. CONCLUSION: This is the first report of the use of zidovudine to treat HIV-negative patients with psoriasis. Although zidovudine was well tolerated, it may be more effective in HIV-positive patients with psoriasis.

Administration, Oral↗
PubMed1994

Analysis of TAP2 and HLA-DP gene polymorphism in psoriasis.

TAP2 is a gene, located between HLA-DP and HLA-DQ, whose products form a transporter molecule involved in endogenous antigen processing. Polymorphic residues have been described in this gene. TAP2 is of particular interest because its involvement in antigen presentation makes it a candidate for a disease susceptibility gene. In psoriasis, two clinical subtypes analogous to the situation in diabetes type I with early onset and family history and type II with later onset and without family history have been described. We have previously shown that type I but not type II psoriasis is associated with the HLA-DRB1*0701/2, -DQA1*0201, -DQB1*0303 haplotype. To investigate whether this haplotype extends to include particular TAP2 and/or DP alleles, we tested the TAP2 and HLA-DP alleles of a control group (n = 199), patients with psoriasis type I (n = 66), and patients with psoriasis type II (n = 35) by hybridization with SSOs. Our data show that there is no significant correlation between TAP2 and/or HLA-DP gene polymorphism and psoriasis type I and/or type II. We conclude that disease association in type I psoriasis is associated with the extended haplotype HLA-B57, -Cw6, -DRB1*0701/2, -DQA1*0201, -DQB1*0303.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Psoriatic lesions in patients with chronic liver disease are distinct from psoriasis vulgaris lesions, as judged on basis of integrin adhesion receptors.

Psoriatic lesions are relatively frequent in patients with chronic liver disease. Furthermore, therapy with interferons tends to exacerbate the symptoms. The pathogenesis of psoriatic lesions is unclear. An important question is whether such lesions may be linked to the underlying chronic liver disease in these patients, or whether they are incidental manifestations of psoriasis vulgaris. We collected biopsy specimens from involved and uninvolved skin areas of chronic liver disease patients with psoriatic manifestations, as well as from psoriasis vulgaris patients, and investigated the patterns of integrin adhesion receptors by means of immunohistochemical methods. Integrin expression is known to be characteristically altered in psoriasis vulgaris. We found some of these changes in chronic liver disease psoriatic lesions-namely pericellular redistribution and suprabasal expression of the basement membrane receptor alpha 6 beta 4 and of the intercellular integrins alpha 2 beta 1 and alpha 3 beta 1. However, psoriasis vulgaris causes two other typical changes: One is the induction of the prototype fibronectin receptor alpha 5 beta 1, and the other is the alteration of integrin expression in areas of the epidermis that are macroscopically normal. These two changes were not found in chronic liver disease psoriasis biopsy specimens in 14 patients investigated. Thus integrin expression may be useful in differentiating chronic liver disease psoriatic lesions from psoriasis vulgaris lesions. Even though the two types of lesions are indistinguishable on inspection or by their histological features, they may be caused by distinct pathogenetic mechanisms. It remains to be seen whether the underlying chronic liver disease has a role, albeit indirect, in such mechanisms.

Aged↗
PubMed1990

Psoriasis: highly reactive early cellular inflammation.

Psoriasis is the result of highly reactive early cellular inflammation. Psoriasis simultaneously has a rapidly proliferating epidermis, a vigorous acute inflammatory reaction, an accelerated rate of dermal breakdown and repair, and vascular and fibroblast proliferation. Understanding the primary role of early cellular inflammation allows explanation of other factors. All clinical, experimental and therapeutic facts can be explained on this basis. There are extensive biologic changes. Early cellular inflammation is influenced by genetic and environmental factors. It is proposed that the defect is quantitative rather than qualitative. Psoriasis commonly localizes at sites of injury. Several authors have noted that the first histologic change in psoriasis is the spurting of granulocytes from the dermal papillae. This is a cyclical event. Connective tissue-active peptides released from granulocytes produce a ninefold increase in the size of the dermal papille. This results in a ninefold increase in the size of the germinative cell base of the epidermis. The vast literature on rapid epithelial proliferation in psoriasis measures a secondary phenomenon. The concept presented does not provide an answer to the biochemistry of early cellular inflammation except to point out the initial importance of dilution of tissue fluids. The author considers early cellular inflammation to result from multiple, simultaneous, overlapping, amplifying and inhibitory systems. There are multiple ways to arrive at the final biologic effect which is too essential to depend on a single series of events. There is a large amount of empiric knowledge on psoriasis which can aid in understanding early cellular inflammation.

Animals↗
PubMed2004

A phase II multicenter clinical trial of systemic bexarotene in psoriasis.

BACKGROUND: Bexarotene, a novel and unique synthetic P, RXR-selective retinoid, is available as a treatment for cutaneous T-cell lymphoma. In psoriasis, a common retinoid-sensitive disease, no data are available on bexarotene treatment. OBJECTIVE: In this phase II study we investigated the safety, tolerability, and effectiveness of bexarotene in psoriasis at doses of 0.5 to 3.0 mg/kg/day. METHODS: Fifty patients with moderate to severe plaque-type psoriasis were treated with bexarotene in 4 sequential dose-defined panels of 12-13 patients at doses of 1.0, 2.0, 0.5, and 3.0 mg/kg/day for 12-24 weeks. Patients were monitored for safety and clinical efficacy. RESULTS: No serious adverse events related to the drug occurred. Bexarotene was well tolerated in most patients. Most frequently observed adverse events related to bexarotene were hypertriglyceridaemia (56%) and a decrease in free T4 serum levels (54%). Significant improvement of psoriasis after bexarotene at all doses was confirmed by a modified psoriasis area and severity index (mPASI), plaque elevation (PEL), and physician's global assessment (PGA). Overall response rates (> or =50% improvement) for mPASI, PEL, and PGA were 22%, 52%, and 36%, respectively. No significant dose-response effect was established for these parameters. CONCLUSION: The present study indicates an anti-psoriatic effect of bexarotene. Further studies are necessary to assess the optimal dose and the potential for bexarotene as a new therapy for psoriasis.

Adult↗