摘要:

SummaryThe hereditary transmission of psoriasis is suggested by epidemiological data and familial association, but remains incompletely defined, not appearing to follow simple autosomal dominant or recessive patterns. The confusion may be due to a multifactorial inheritance, or to inheritance of only a ‘predisposition’ to disease which requires an environmental stimuli for expression. Recent advances in genetic mapping indicate genetic heterogeneity, and suggest that definition of psoriasis at the level of the gene may soon be possible. Two of the three major pathogenic features of psoriasis—abnormal keratinocyte differentiation and hyperproliferation of keratinocytes—are secondary to altered growth and maturation kinetics related to the normal wound healing process. The third major pathogenic feature—infiltration of inflammatory components into the skin—can be explained by keratinocyte release of a wide variety of cytokines, immune and inflammatory modulators. Three theories have been proposed for the relationship between epidermal keratinocyte and immunocyte activation. The first theory proposes direct activation of epidermal keratinocytes by physical, chemical, or ultraviolet injury, increasing the synthesis and release of cytokines. which trigger T‐lymphocyte activation in an antigen‐independent fashion. The other two theories propose persistent T‐lymphocyte stimulation as a result of either antigen/superantigen presentation by antigen‐presenting cells, or as a result of autoreactivity. One or more of these mechanisms may he operative in different patients, at different times, or in response to different environmental stimuli. Also, the genetic heterogeneity of psoriasis suggests that different mechanisms could be linked to different genetic loci. Advances in understanding the aetiology and pathogenesis of psoriasis suggest the possibility of innovative,

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1996.tb15660.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryCyclosporin is a highly effective treatment for psoriasis, atopic dermatitis and many other inflammatory dermatoses. Absorption of cyclosporin from the traditional Sandimmun® formulation is influenced by many factors, including bile flow, food and gastrointestinal motility. As a consequence, the bioavailability of Sandimmun® is low and highly variable, both within and between patients. Neoral® is a microemulsion preconcentrate formulation that has self‐emulsifying properties and immediately forms a microemulsion in aqueous fluids, allowing rapid and consistent absorption of cyclosporin from the gastrointestinal tract. Benefits in dermatology are likely to be more patients responding at lower doses, a faster onset of action and a more predictable response to a given dose allowing for fewer dose adjustments. In the future these benefits of Neoral® may lead to the simplified management of cyclosporin treatment and less frequent safety monit

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1996.tb00701.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryCyclosporin has been shown to be highly effective in psoriasis, atopic dermatitis and numerous other dermatoses. Depite the effectiveness of cyclosporin, the response varies somewhat between individuals. Some may not respond, and often this is linked with unpredictable absorption of the traditional formulation. Cases of atopic dermatitis and psoriasis previously resistant to cyclosporn have responded wel to a new microemulsified formulation, Neoral®, and formal trials are now underway to investiage its use in these indications. Preliminary data from a clinical trial using the new traditional formulation in this condition, and that repeated short courses of therapy may be well tolerated

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1996.tb00702.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryPsoriasis is a disease of unknown aetiology, affecting approximately 1–3% of the population. In most cases involving relatively localized disease, patients are best managed with either topical therapy alone or topical therapy in combination with UV–phototherapy. However, approximately 35% of patients do not respond well to these conventional treatments or have moderate–to–severe disease requiring more aggressive forms of therapy. The second–generation retinoids, etretinate and its metabolite acitretin, are important additions to the armamentarium of agents used to treat these recalcitrant or severe forms of the disease. Generalized pustular psoriasis generally responds well to high‐dose (0·7–1 mg/kg/day) oral retinoid monotherapy. In contrast, increasing small doses of the retinoid are recommended initially in erythrodermic psoriasis in order not to provoke the disease. Long‐term clinical experience favours a combination treatment of the retinoid with either topical and/or UV irradiation in chronic plaque‐like psoriasis. Both oral retinoids have comparable efficacy and tolerability profiles, and the relapse rates for both drugs are similar. The toxicities associated with both short‐ and long‐term treatment with oral retinoids are significant and include mucocutaneous effects, adverse modulation of serum lipid chemistries, elevation of liver enzymes, and after long–term chronic dosing, skeletal and ligamentous calcification, and hyperostosis. Both etretinate and acitretin, like all retinoids, are known teratogens in animal models, and documented evidence exists for teratogenic activity in humans as well. Consequently, women of childbearing age are strongly advised to avoid pregnancy during treatment and up to 5 years following cessation of therapy with both etretinate and the carboxylic a

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1996.tb15661.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryA comparison was made of the efficacy, tolerability, safety and steady state pharmacokinetics of Sandimmun® in 11 stable atopic dermatitis patients already on Sandimmun®. The study was of an open, crossover design. At entry into the trial, patients were switched to Neoral® for 28 days. Treatment was switched back to Sandimmun® for Days 28 to 42. The morning dose was given fasting, the evening dose after a standard meal. Al measures of eczema severity improved during the Neoral® treatment period. Neoral® was markedly better tolerated with fewer side‐effects. Switching from Sandimmun® to Neoral® at the same dose resulted in less variable pharmacokinetic profiles in both fasted and fed states. There was an increase in bioavailability with better, less variable and faster absorption, with a slightly reducedtmax, a higher meanCmax(+43%) and a higher mean AUC (+30%) in fasted, but not fed patients. Higher trough levels (Cmin) occurred throughout for Neoral® These differences between the two formulations were not associated with any changes in safety parameters. Overall, Neoral® was equivalent or superior to Sandimmun® in tolerability and efficacy when given on a 1:

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1996.tb00703.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryOne reason why so little is known about the epidemiology of atopic dermatitis (AD) is lack of suitable diagnostic criteria. A simple list of diagnostic criteria for AD for use in epidemiological studies has recently been developed by a U.K. working party. These have performed well in hospital validation studies of subjects with skin diseases. This study sought to validate the newly proposed criteria for AD in a population setting by conducting a cross‐sectional survey of 695 schoolchildren aged 3–11 years in three randomly selected primary schools in West Lambeth, London. As a point prevalence measure, the U.K. criteria had a sensitivity of 70%, a specificity of 93%, and a positive predictive value of 47% when compared with a dermatologist's examination findings. Subsequent analysis suggested that most children classified as false positives had suffered from AD in the last year, but were inactive at the time of examination. When adjusted for these cases, the sensitivity and specificity increased to 80 and 97%, respectively, corresponding to positive and negative predictive values of 80 and 97%, respectively. The U.K. diagnostic criteria for AD appear to work well as a 1‐year period prevalence measure in London schoolchildren. Further validation in adults and other countries are n

ISSN:0007-0963    

DOI:10.1046/j.1365-2133.1996.d01-925.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1996.tb15167.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryAn open, randomized trial was performed to determine the optimal dosage schedule with regard to the efficacy and safety of cyclosporin in severe atopic dermatitis. The study also provided clinical experience with regard to the efficacy and safety of long‐term cyclosporin treatment. During a 2‐month dose‐finding period. 78 patients with severe, long‐standing atopic dermatitis received cyclosporin at a dose of either 5 mg/kg per day, decreasing to 3 mg/kg per day (Group A), or 3 mg/kg per day, increasing to 5 mg/kg per day (Group B). Patients were maintained on their optimal dose for a further 10 months. Patients in Group A showed a significantly greater improvement in efficacy parameters over the first 2 weeks than with patients in Group B, but as the dose was decreased in Group A and increased in Group B, these differences were minimized. After 1 year, cyclosporin showed an efficacy of 59.8% in Group A and 51.7% in Group B, assessed by a severity score. Assessed in terms of an area score, these figures were 48.7% and 40%, respectively. Cyclosporin demonstrated a good safety profile during long‐term treatment and was generally well tolerated. The lower starting dosage was not associated with higher dropout rates. This study showed no differences in efficacy or adverse events between the two dosage schedules in long‐ter

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1996.tb00704.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryTazarotene is a topically applied retinoid that targets the skin, the site of the fundamental defect(s) in psoriasis, modulating the major causes of the disease and achieving sustained efficacy. In vitro. binding of tazarolenic acid has been demonstrated to retinoic acid receptors (RARs). the probable molecular target of retinoid action in adult human skin, but not to retinoid X receptors (RARs). In gene activation assays, tazarotene is selective for the RARβ and RARγ subtypes. This selectivity could theoretically limit undesirable effects at the receptor level. In vitro, animal and clinical evidence reveals that topical tazarotene modulates all three pathogenic factors in psoriasis: abnormal keratinocyte differentiation, hyperproliferation. and increased expression of inflammatory markers. Tazarotene is minimally absorbed systemically after topical administration. Tazarotene is rapidly metabolized by esterase metabolism to its active free‐acid form, tazarotenic acid, which has a relatively short elimination half‐life (1–2h). The pharmacokinetic profile of tazarotenic acid is predictable, with no significant accumulation. In preclinical toxicity studies, high topical doses produced only reversible topical irritation, and lower doses were well tolerated. Topical doses were neither carcinogenic nor teratogenic, had no effect on fertility or general reproduction, and were not phototoxic. sensitizing, or photoallergenic. The pharmacological selectivity of tazarotene and limited systemic exposure result in minimal systemic effects, while the lesser cytotoxic effects (relative lo other retinoids) result in reduced local

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1996.tb15662.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryAtopic eczema affects 2.3% of the U.K. population. We have carried out a community study in a semi‐rural area to assess its economic impact. One hundred and fifty‐five patients with atopic eczema were identified and expenditure was assessed over a 2‐month period. The mean personal cost to the patient was £25.90, while the mean cost to the health service was £16.20. There were 58 lost working days and 17 lost school days. A cohort of 10 severely affected patients attending the Royal Infirmary of Edinburgh were studied; each patient spent, on average, £325 in 2 months, and lead to a mean health service expenditure per patient of £415, in 2 months. If these results were extrapolated to the U.K. population, the annual personal cost to patients with atopic eczema would be £297m, the cost to the health service would be £125m, and the annual cost to society of lost working days would be £43m, making the total expenditure on atopic

ISSN:0007-0963    

DOI:10.1046/j.1365-2133.1996.d01-970.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY