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Notes: Thirteen patients with severe persistent psoriasis, intolerant of, or unresponsive to, other current treatments have been treated with cyclosporin (Cys) for periods varying from 12–25 (mean 18) months. The dose ranged from 1–4 mg/kg/day (mean 2.8 mg). There was a 72% reduction in the mean PASI score at 4 weeks, and at the end of the study, an 81% reduction. Adjuvant therapy with topical steroids was used in 11 of the 13 patients after the first 3 months of Cys treatment to persistent patches on an intermittent basis with beneficial effect. Six patients developed mild to moderate hypertension, in three this was controlled by a reduction in the dose of Cys, and in the other three by hypotensive agents. The mean serum creatinine rose from 72 to 90μM/1 during the study. Hypertrichosis occurred in seven of the 13 patients. Low dosage Cys is an effective treatment for clearing psoriasis and maintaining improvement on a long-term basis.

Notes: Sequential skin biopsies from six patients with severe psoriasis were studied during treatment with cyclosporin. Four of the patients cleared completely and the remaining two showed a marked improvement. A subset of dendritic cells, HLA-DR+ but lacking the T6 antigen characteristically expressed by Langerhans cells (DR+ 6-), was observed in lesional epidermis. They disappeared during treatment, before clinical improvement was apparent and at a rate which correlated with clearance of psoriasis. These cells were not found in normal or uninvolved psoriatic epidermis and their number in lesional skin appeared to be related to the clinical severity of the disease. Total numbers of CD4 and CD8, and HLA-DR+ CD8 T cells were substantially reduced in both epidermis and dermis prior to clinical improvement. In contrast, there was generally no decrease in the number of HLA-DR + CD4 T cells in the epidermis during resolution, whereas these cells were reduced by an average of 68% in the dermis. The beneficial effects of cyclosporin in psoriasis further support the hypothesis that T cells play a central role in the pathogenesis of psoriasis. The cellular changes observed in the skin during cyclosporin treatment may help to elucidate the effects of this drug on immunoregulatory mechanisms in man.

Notes: Background  Fumaric acid esters (FAE) have been used to treat severe psoriasis in northern Europe for over 20 years. A recent systematic review has shown FAE to be an effective systemic treatment for severe psoriasis. However, FAE remain unlicensed in the U.K.Objectives  To present data relating to the efficacy and tolerability of FAE in severe psoriasis and report our experiences of FAE therapy at one U.K. centre.Methods  Patients who had received FAE for severe psoriasis at one U.K. regional referral centre between June 1999 and October 2003 were identified from pharmacy records. Their records were analysed retrospectively.Results  Fifty-eight patients (25 women, 33 men) were identified. Fifty-five (95%) of the 58 patients had previously used other systemic antipsoriatic therapies with over 70% previously using two or more agents. Thirty-two patients (55%) showed improvement in their psoriasis with 10 (17%) being rated as ‘clear’ or ‘virtually clear’ by the attending physician. No improvement was seen in 28% patients and 16% showed worsening of their disease. Adverse events were common and were reported in 66% patients. These mainly consisted of abdominal pain (61%), diarrhoea (55%), flushing (45%), nausea (21%) and malaise (15%). They led to discontinuation of treatment in 15 patients after a mean period of 4·7 months. Lymphocytopenia developed during treatment in 57% of patients, all of whom had had a baseline value within the normal range. In only one patient was this considered severe enough to warrant withdrawal of treatment.Conclusions  Our study has shown that FAE are an effective therapy in selected patients with severe psoriasis, even in those who have previously been intolerant of systemic therapy or where it has failed.

Notes: Background  Psoriasis is characterized by symmetry of plaques and modulation of multiple genes within those plaques.Objectives  We compared gene expression profiles of plaques of psoriasis at different anatomical sites for both symmetrical and asymmetrical disease to ascertain whether the same genes were expressed.Methods  Gene expression profiles were analysed in biopsies from lesional and uninvolved skin from two groups of patients with either predominantly symmetrical or truncal plaques of psoriasis vulgaris, and from normal skin of healthy volunteers. Genomic analyses were performed using cDNA array and kinetically monitored reverse transcriptase-initiated polymerase chain reaction (kRT-PCR) approaches. A cluster of genes upregulated in involved psoriasis skin as compared with normal skin was identified using each of these two technologies.Results  Clustering of patients based on their gene expression profile did not reveal any correlation with family history of psoriasis, age at onset or association of psoriasis with arthritis. There was no difference in gene expression profile between the type (symmetrical vs. truncal) or location (left vs. right side of body) of psoriatic plaques. Gene expression profiles of involved psoriatic skin analysed by kRT-PCR analysis did correlate with both global (Psoriasis Area and Severity Index) and local (erythema, desquamation and plaque elevation) clinical severity.Conclusions  These results indicate that it may be feasible to analyse the molecular effects of pharmacological agents on psoriatic skin in ‘minizone’ protocols, that the obtained data can be correlated with clinical severity and that plaques of psoriasis in the same individual express the same genes.

Notes: An understanding of the molecular basis of angiogenesis is key to the appreciation of many of the advances made in the field of neovascularization over the past two decades. The sequence of events involved in angiogenesis includes: (i) increased vascular permeability and leakage; (ii) degradation of basement membrane; (iii) endothelial cell proliferation and migration through the surrounding extracellular matrix; and (iv) maturation and stabilization of the newly formed vessel bed. This review provides an update on the molecular basis of such pathways in the skin, with particular emphasis on the endothelial cell-specific vascular endothelial growth factor and angiopoietins as modulators of angiogenesis that can be targeted in therapy of cutaneous disease.

Notes: Summary Background  As psoriasis patients often require continuous treatment optimal therapy has to provide efficacy and a good safety profile over the long term.Objectives  The aim of this multicentre study was to assess the efficacy, safety and tolerability of tacalcitol (4 µg g−1) ointment (Curatoderm®, Hermal, Reinbek, Germany) applied once daily over a treatment period of 18 months.Patients and methods  Efficacy parameters were Psoriasis Area Severity Index (PASI), based on summed scores of erythema, infiltration and scaling and total body surface involvement (TBI). Safety assessment included serum levels of calcium, parathyroid hormone, calcitonin, 1,25-dihydroxy vitamin D3 (calcitriol); urinary calcium, creatinine, calcium/creatinine ratio in spot and 24-h urine and urinary α1-microglobulin. A group of 304 patients with chronic plaque psoriasis, covering between 7% and 20% of the body surface area was included for the initial treatment phase of 3 months. Of the 257 patients who completed the initial 3 months, 197 patients continued in a second treatment phase of 15 months.Results  Tacalcitol treatment proved to be effective in reducing the severity of psoriasis and maintained therapeutic response over the study period. The median PASI fell from 9·5 to 4·6 at month 3 and to 3·25 at month 18 (P 〈 0·0001). The median improvement in TBI was 30% at month 3 and 50% at month 18. In no patient was there any relevant disturbance of calcium homeostasis. There were no significant changes in mean values of serum calcium, parathyroid hormone and calcitriol. Additionally no significant changes in 24-h urinary excretion evaluation were observed. There was no correlation between levels of serum calcium or urinary calcium and amount of tacalcitol ointment used, even in the patients requiring the largest amounts of ointment (up to 13 g day−1 and up to 20% of body area affected). Treatment was generally well tolerated and there were no serious or unexpected adverse events reported. However, discontinuation of treatment as a result of skin irritation was seen in 5·9% of patients. The greatest frequency of cutaneous side-effects occurred during initial treatment and the incidence decreased markedly as the treatment was well-tolerated with continued use.Conclusions  Tacalcitol ointment once daily was demonstrated to be efficacious, safe and well tolerated in the long-term control of plaque psoriasis in patients with up to 20% body surface involvement.

Notes: SummaryThe primacy of the immune system in the pathogenesis of psoriasis is a well-established concept to the extent that psoriasis has been classified as a T-cell-mediated, autoimmune disease. An explosion of knowledge concerning immunological events in psoriasis and the clinical efficacy of immunologically directed therapies, such as cyclosporin, support this concept. Armed with this understanding and modern biotechnology, novel interventions have been developed to treat psoriasis. The aim of these therapies is to provide selective, immunologically directed intervention with the hope that such specificity will result in fewer side-effects than traditional therapies. Of interest and importance, these pharmaceutical interventions also act as a form of investigational tool in psoriasis. Their relative efficacy in the psoriatic process provides useful insights into the hierarchial importance of immune events in the disease process and recent evidence suggests that innate rather than acquired immunity has a key role. This article reviews recent developments in immune-based therapies for psoriasis.

Notes: Summary Background Patients with psoriasis may experience significant psychological and social disabilities. Stress or distress are proposed aggravators of the disease process in psoriasis. Preliminary studies to date have suggested that adjunctive psychological therapies may be effective in the clinical management of psoriasis. Objectives To examine whether a 6-week multidisciplinary management approach, the Psoriasis Symptom Management Programme (PSMP) for patients with psoriasis improves clinical severity of psoriasis and its associated psychological distress and disability. Methods In a case–control study, patients with psoriasis attending an out-patient psoriasis speciality clinic chose to receive standard psoriasis treatment alone (n = 53) or to enter the PSMP as an adjunct to standard therapy (n = 40). They were assessed at baseline, at the end of the 6-week PSMP and after 6 months follow-up. Results As compared with standard treatment alone, analysis of covariance indicated that participation in the PSMP resulted in a greater reduction in clinical severity of psoriasis (P = 0·001), anxiety (P = 0·001), depression (P = 0·001), psoriasis-related stress (P = 0·001) and disability (P = 0·04) at 6 weeks and 6 months follow-up. Conclusions The management of the physical aspects of psoriasis and its psychological effects are significantly improved for patients who opt for a 6-week integrated multidisciplinary approach. Furthermore, the techniques learnt by participation in the PSMP facilitate continued control of psoriasis for at least 6 months.