摘要:

Psoriasis is a chronic inflammatory multifactorial disease and the precise molecular defects causing psoriasis remain unclear; but a genetic predisposition and environmental factors are involved in the pathogenesis. A strong genetic component is found in certain individuals and the inheritance of psoriasis can be classified as autosomal dominant with variable penetrance. Clinically, psoriasis represents a collection of similar disorders with a variable phenotype, making investigation at the molecular level extremely complex. Lesions are characterized by hyperproliferation and abnormal epidermal differentiation, together with a strong inflammatory and immunological component. However, studies over the last 20 years have failed to find molecular alterations that are either specific to the psoriatic lesion or characteristic of uninvolved skin. Trauma, stress and chemicals are all known to precipitate psoriasis in susceptible individuals, but the molecular mechanisms are not understood. The accumulation of inflammatory cells in the epidermis and altered dermal vessels are major characteristics, and these changes are driven by release of cytokines and growth factors. Many investigations have shown that the process of epidermal differentiation in the lesion is aberrant. Increased transit time of cells through the epidermis combined with a shift to the‘hyperproliferative state’prevents the keratinocyte from completing the preprogrammed molecular events necessary for normal terminal differentiation. Calcium and its binding proteins are important in terms of providing the driving force for epidermal differentiation, and vitamin D3analogues have proved to be useful therapeutic agents in psoriasis. However, while they do reduce proliferation and stimulate epidermal differentiation, the precise mechanisms by which these agents work is also unknown although they do affect T-helper cell populations and may moderate the lymphocyte drive associated with the lesion. Every psoriatic patient presents an individual problem in terms of treatment as there is a wide variation in the type, extent, duration and history of the disease. However, while topical therapy with a variety of regimens is preferred, difficult cases do require more aggressive systemic therapy. It is indisputable that a further understanding of the molecular pathogenesis of psoriasis, the identification of genes linked to the condition and an appreciation of how uninvolved psoriatic skin differs from normal will have an impact on both how we view and treat this disfiguring skin disorder. Only when we have a complete picture of the events that initiate and drive the psoriatic lesion will we be able to develop effective regimens to control this condition.

ISSN:0954-6634    

DOI:10.3109/09546639609080595

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Informal subjective clinician assessments of the response of patients to one or another treatment are often over optimistic. There are many ways in which more realistic evaluations can be made, and this article reviews some of these. It is concluded that no single measurement is ideal. An objective parameter, such as plaque thickness as measured by ultrasound, backed up with a functional assessment, as with the Psoriasis Disability Index, constitutes the best compromise.

ISSN:0954-6634    

DOI:10.3109/09546639609080596

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Calcitriol (1α,25-dihydroxyvitamin D3) ointment has been shown to be effective in the treatment of chronic plaque psoriasis. The present open study was designed to assess the safety and tolerability of 3μg/g calcitriol ointment applied twice daily over treatment periods of up to 78 weeks. In 253 evaluable patients with chronic plaque psoriasis no clinically relevant changes were observed in the baseline/endpoint analyses of any laboratory tests, including measurements of calcium homeostasis such as serum levels of total calcium, albumin-adjusted total calcium and phosphorus and plasma calcitriol levels. The treatment was well tolerated with no serious adverse events occurring during the course of the study. Eight patients withdrew due to adverse events which, though not serious, were thought to be treatment related: seven patients showed skin irritation reactions and in one case a mild, transient, asymptomatic hypercalcaemia was observed. Assessments of global severity, global improvement and Psoriasis Area and Severity Index (PASI) scores confirmed the therapeutic efficacy demonstrated in earlier studies. In conclusion, the twice daily application of 3μg/g calcitriol ointment was safe, well tolerated and effective in the long-term treatment of chronic plaque psoriasis, and did not affect systemic calcium metabolism during prolonged treatment.

ISSN:0954-6634    

DOI:10.3109/09546639609080597

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Psoriatic lesions on the face can be particularly distressing for patients as they are clearly visible and difficult to hide or disguise. The treatment of such lesions is also problematic as many of the most widely used agents, such as topical corticosterolds, cannot be used routinely on facial skin. Local and systemic safety, tolerability and efficacy of twice daily application of 3μg/g calcitriol ointment in the treatment of moderate to severe facial, hairline and retroauricular chronic plaque psoriasis were assessed in an open study in ten patients. The duration of treatment was 6 weeks. The treatment was well tolerated, and no serious adverse events occurred. One patient had a transient mild skin irritation reaction and transient moderate hair loss, and another patient had transient mild seborrhoeic dermatitis near the right nose fold. In the baseline/endpoint comparison no statistically significant changes were observed in the mean values of serum total calcium, serum albumin-adjusted total calcium, serum phosphorus, plasma calcitriol and 24-h urinary calcium and phosphorus excretion. Twice daily applications of 3μg/g calcitriol ointment appeared to be very effective in the treatment of moderate to severe facial, hairline and retroauricular chronic psoriatic plaques. The treatment resulted in statistically significant reductions in the severity of the skin symptoms (scaling, erythema, induration, pruritus and overall severity). At the end of the treatment period all patients showed improvement of psoriatic plaques: clearance of plaques was observed in 40% of patients, considerable or definite improvement in 50% and minimal improvement in 10%. In addition, cosmetic acceptability of the calcitriol ointment was judged to be good. The results of this study indicate that twice daily use of 3μg/g calcitriol ointment is safe, effective and well tolerated in the treatment of facial, hairline and retroauricular chronic plaque psoriasis.

ISSN:0954-6634    

DOI:10.3109/09546639609080598

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

The effects of calcitriol and calcipotriol ointments on calcium homeostasis in rats were investigated. Three groups of five rats received 4 daily applications of either calcitriol ointment (3μg/g), calcipotriol ointment (50μg/g) or vehicle on the back (area 75 cm2). Blood and urine were collected during treatment and for 7 days after the last dose. Calcitriol ointment did not affect any of the parameters studied. Calcipotriol ointment caused a significant increase in urinary calcium and phosphate excretion and severe downregulation of endogenous calcitriol levels occurred, up to 7 days after the last dose. Calcipotriol could still be detected in the last plasma sample. In order to substantiate the safety of calcitriol ointment in clinical practice, plasma calcitriol levels were determined in clinical trial patients. Over 2000 samples from more than 400 patients with chronic plaque psoriasis were analysed. There was no indication of increased plasma calcitriol when patients were treated with calcitriol ointment (3μg/g twice daily) for up to 78 weeks at body surface areas up to 6000 cm2. At higher body surface areas insufficient data were available. It is concluded that calcitriol ointment does not affect calcium homeostasis in rats, whereas calcipotriol ointment has a prolonged effect on it. Plasma calcitriol levels in clinical trials indicate that calcitriol ointment is a safe treatment for chronic plaque psoriasis.

ISSN:0954-6634    

DOI:10.3109/09546639609080599

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor