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Background Anti-tumour necrosis factor ( TNF)-α therapies have revolutionized the treatment of psoriasis; however, up to 50% of patients do not respond satisfactorily. Identification of pharmacogenetic markers of treatment response is an important stop in the development of individually tailored treatment. The objective of this study was to assess the association of human leucocyte antigen ( HLA)- C, killer immunoglobulin receptor ( KIR) and vitamin D receptor ( VDR) genotypes with response to treatment by etanercept and adalimumab. Methods This was a study of 138 patients with severe chronic plaque psoriasis who were treated with etanercept and/or adalimumab. Patients were classified as responders if they achieved a 75% reduction in PASI ( PASI75) or were almost clear of psoriasis after 24 weeks of therapy. The frequencies of HLA- C and KIR haplotypes and VDR polymorphisms were compared in responders and nonresponders. The frequency of all HLA- C and KIR genotypes were compared between the 138 patients with psoriasis and 247 healthy donors. Results The number of patients classified as responders was 46 of 94 (49%) in the etanercept group and 50 of 76 (66%) in the adalimumab group. None of the HLA- C, KIR or VDR genotypes examined was predictive of treatment response. Compared with healthy controls, patients with psoriasis were more likely to have the HLA- C*06 genotype ( P < 0.001) and less likely to have the HLA- C*07 genotype ( P < 0.001), whereas there was no significant difference in frequencies of any KIR subtype. Conclusions Using the candidate gene approach to identify biomarkers of treatment response in psoriasis may have limited utility. This was a small study with limited power. Future larger studies are needed to further examine these findings and to explore alternative approaches to identify predictors of treatment response to biological agents. [ABSTRACT FROM AUTHOR]

There is considerable variability in the number of exposures of narrowband ultraviolet B (NB-UVB) needed to clear psoriasis and in the duration of remission. We assessed clinical parameters as predictors of the number of exposures needed to clear psoriasis and of the duration of remission. The influence of genetic polymorphisms of the vitamin D receptor (VDR) on treatment response was also evaluated. This was a prospective study of 119 patients with chronic plaque psoriasis treated with NB-UVB until clearance was achieved. They were then followed for up to 1 year or until relapse occurred. The frequency of the Fok1, Apa1, Bsm1, Taq1 and rs4516035 polymorphisms of the VDR gene was assessed in 93 of the 119 patients. Of the 119 patients, 105 completed the course of phototherapy. Using an intention to treat analysis, 83% of the initial cohort (99 of 119 patients) achieved clearance, in a median of 26 exposures (interquartile range 19-35) with a median remission duration of 16 weeks (interquartile range 9-22). Factors significantly associated with a lower number of exposures to clearance included a lower baseline Psoriasis Area and Severity Index ( P = 0·004), lower baseline Dermatology Life Quality Index ( P = 0·047), female sex ( P =0·043), lower body weight ( P = 0·008), and a higher number of previous courses of TL-01 ( P = 0·005). The only clinical factor influencing remission duration was number of exposures ( P = 0·0009), with a decreased remission duration in those who required a greater number of exposures to clear. The Taq1 VDR polymorphism (rs731236) also significantly predicted remission duration ( P = 0·038). Patients homozygous for the C allele, which is associated with decreased activity of the VDR, had a shorter remission duration than those heterozygous for the allele ( P = 0·026) and those homozygous for the T allele ( P = 0·013). This study highlights the fact that both genetic and clinical parameters are important in determining treatment outcomes in psoriasis. [ABSTRACT FROM AUTHOR]

Background Survivin, an inhibitor of apoptosis protein (IAP), has been implicated in endothelial cell stability, through inhibition of apoptosis and in cell proliferation. Objectives To evaluate the effect of antitumour necrosis factor (TNF)- α therapy on survivin expression in psoriasis skin at 0, 2 and 12 weeks after infliximab therapy. Methods Skin biopsies were obtained from 16 patients; 11 also had arthritis with active skin/joint disease. Clinical scores [Psoriasis Area and Severity Index (PASI), involved body surface area (BSA), Disease Activity Score (DAS28) and Health Assessment Questionnaire] were recorded. Inflammatory infiltration and survivin protein expression were examined and graded by immunohistochemical staining, and mRNA levels were determined by real-time polymerase chain reaction. Results Survivin mRNA and protein were demonstrated in all baseline lesional biopsies. Survivin mRNA and protein expression was significantly greater in lesional compared with nonlesional baseline skin ( P < 0·05). Differential cellular localization of survivin was demonstrated with cytoplasmic survivin protein expression localized to the perivascular/endothelial regions and strong nuclear staining localized in the basal layer of the epidermis. Infliximab produced a dramatic clinical response in skin and joints ( P < 0·05), paralleled by significant reduction in the inflammatory infiltrate and survivin protein expression ( P < 0·05) which was reflected at the mRNA level where expression was significantly reduced by week 12 ( P < 0·01). Survivin protein levels before and after treatment significantly correlated with PASI ( r = 0·478, P < 0·05) and BSA scores ( r = 0·528, P < 0·024). PASI strongly correlated with BSA ( r = 0·949, P < 0·0001) and DAS28 ( r = 0·717, P < 0·002) scores. Conclusions Survivin correlates with disease activity in patients with psoriasis and is significantly downregulated following anti-TNF- α treatment. Understanding the role of IAPs in cell survival/antiapoptosis and proliferation mechanisms may provide important insights into downstream therapeutic targeting in inflammation. [ABSTRACT FROM AUTHOR]

Summary The use of cyclosporin A (CSA) for the treatment of severe psoriasis is well established. However its use is limited by its adverse effects, especially nephrotoxicity. We reviewed 28 patients treated with CSA for severe psoriasis over an 11-year period. All patients were on long-term CSA treatment (median duration 55.5 months). Twenty patients developed renal impairment which required discontinuation of treatment in seven. Twelve patients' renal function stabilized on dose reduction and one improved. Sixteen patients developed hypertension. For this small group of patients with severe psoriaisis, recalcitrant to other treatments, CSA afforded better quality of life which they otherwise could not enjoy. Although this comes at a cost with the development of renal impairment we feel that such patients can be continued on CSA provided that they are under the combined care of a dermatologist and a nephrologist. [ABSTRACT FROM AUTHOR]

Focuses on an article published in the 'Clinical and Experimental Dermatology' periodical, which described a clinical case of dermatomyositis-like eruption and leg ulceration caused by hydroxyurea in a patient with psoriasis. Pathogenesis; Characterization of the disease condition.

Investigates the relapse rate and long-term management of plaque psoriasis after treatment with photochemotherapy and dithranol. Reduction of relapse rates; Statistical difference in relapse rates between the two maintenance schedules; Efficacy of maintenance treatment on psoriasis.

Twenty-one patients with chronic plaque psoriasis were treated with bath 8-methoxypsoralen (8-MOP) and ultraviolet A (UVA). Clearing was achieved in sixty per cent of patients which was less than would be expected with oral 8-MOP. The treatment was well tolerated and was preferred by those who had previously been treated with oral psoralen. The cumulative dose of UVA was only one-fifth that expected with oral 8-MOP. [ABSTRACT FROM AUTHOR]