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PubMed1986

Drugs in exacerbation of psoriasis.

Drugs that have been associated with the precipitation or exacerbation of psoriasis include lithium, beta adrenergic receptor blocking agents, and antimalarials. The withdrawal of corticosteroids has been reported to activate pustular psoriasis. Nonsteroidal anti-inflammatory drugs, such as indomethacin, have recently been reported to exacerbate psoriasis, although additional well-controlled studies are still needed. Drugs used for treatment of psoriasis will sometimes cause a flare because of irritation, phototoxicity, or hypersensitivity reaction resulting in a Koebner phenomenon. Because psoriasis is a very complex disease and its activity is often unpredictable, clinical studies on adverse drug effects on psoriasis have been difficult to conduct. This review evaluates clinical, histologic, and biochemical evidence in the literature for drug-associated onset or exacerbation of psoriasis.

Adrenal Cortex Hormones↗
PubMed1997

Comparison of psoralen-UVB and psoralen-UVA photochemotherapy in the treatment of psoriasis.

BACKGROUND: PUVA treatment of psoriasis is usually given with broad-band fluorescent UVA lamps. Narrow-band UVB exposure after oral methoxsalen has been shown to achieve a greater therapeutic response in psoriasis than identical UVB exposure given without psoralen. OBJECTIVE: The purpose of this study was to compare conventional PUVA with psoralen-UVB therapy in psoriasis. METHODS: We studied 100 patients with plaque-type psoriasis who were randomly selected to receive either conventional psoralen-UVA or psoralen-UVB treatment. RESULTS: No significant difference was found between the two treatments in the proportion of patients whose skin cleared during treatment or in the number of exposures required for clearance of psoriasis. As expected, the cumulative UV dose for clearance was smaller in the group treated with UVB compared with those receiving UVA. Side effects and disease status at 3 months after the end of treatment were similar for the two groups. CONCLUSION: Psoralen-UVB treatment of psoriasis is as effective as conventional PUVA. The mechanism of psoralen-311 nm UVB action on psoriasis requires study to predict the long-term safety of this treatment.

Adult↗
PubMed1997

The impact of psoriasis on the quality of life of patients from the 16-center PUVA follow-up cohort.

BACKGROUND: The impact of psoriasis on the quality of life of patients is likely to be principally related to alterations in individual appearance and consequent psychosocial disability. Quantifying the impact of psoriasis and related changes from therapy would help in the selection of optimal management. OBJECTIVE: Our purpose was to evaluate the impact of psoriasis on patients with severe disease who have had photochemotherapy (PUVA). METHODS: In 1979 we interviewed 877 of 988 still participating patients who were enrolled in 15 of 16 centers in the PUVA Follow-up Study. We determined the impact of psoriasis on quality of life with a questionnaire that had been modified to incorporate measures of impairment that are likely to be affected by cutaneous disease. RESULTS: Psoriasis had substantial impact on the quality of life. Women were more likely than men to report impairment in quality of life dimensions. The impact of disease decreased with increasing age. Moderate to high relative impact on total quality of life was more often reported by patients who had recently used UVB phototherapy than by those using PUVA or methotrexate. CONCLUSION: Psoriasis has a substantial impact on the quality of life. This impact seems to decrease with increasing age. Use of specific treatments are also associated with the extent to which psoriasis affects quality of life.

Aged↗
PubMed1997

Bath-5-methoxypsoralen-UVA therapy for psoriasis.

BACKGROUND: After oral intake, 5-methoxypsoralen (5-MOP) is as effective as 8-MOP for PUVA therapy for psoriasis, with a lower incidence of acute cutaneous side effects. OBJECTIVE: We compared bath-water delivery of 5-MOP and 8-MOP for photochemotherapy of psoriasis. METHODS: Twenty-two patients underwent phototesting with 0.0003% 5-MOP or 8-MOP aqueous solutions. Twelve patients with palmar psoriasis were studied with a side-to-side comparison, and 10 patients with recurrent plaque-type psoriasis were treated with one therapy or the other. RESULTS: Minimal phototoxic dose (MPD) values were 2.8 +/- 1.2 J/cm2 with 8-MOP and 2.0 +/- 1.2 J/cm2 with 5-MOP (p < 0.01). Both therapies cleared palmar lesions but 8-MOP required more UVA irradiation (46.3 +/- 21.0 J/cm2 vs 30.2 +/- 21.5 J/cm2; p < 0.01) and more exposures (21.0 +/- 6.0 vs 17.0 +/- 5.0; p = 0.02). Bath-5-MOP-UVA was also more effective in the treatment of plaque-type psoriasis (cumulative UVA doses, 56.8 +/- 39.2 vs 59.1 +/- 27.9 J/cm2; number of exposures, 20.0 +/- 5.7 vs 21.6 +/- 4.7), but these differences were not significant (p = NS). Patients developed an intense tan significantly earlier with 5-MOP than with 8-MOP (3.5 +/- 0.5 weeks vs 4.4 +/- 0.5 weeks; p < 0.01). CONCLUSION: Bath-5-MOP-UVA was more phototoxic than bath-8-MOP-UVA. It was more effective in the treatment of palmar psoriasis, whereas its greater pigmentogenic activity appeared to have an adverse effect on therapeutic effectiveness in the treatment of plaque-type psoriasis.

5-Methoxypsoralen↗
PubMed1998

Omega-3 fatty acid-based lipid infusion in patients with chronic plaque psoriasis: results of a double-blind, randomized, placebo-controlled, multicenter trial.

BACKGROUND: Profound changes in the metabolism of eicosanoids with increased concentrations of free arachidonic acid (AA) and its proinflammatory metabolites have been observed in psoriatic lesions. Free eicosapentaenoic acid (EPA) may compete with liberated AA and result in an antiinflammatory effect. OBJECTIVE: Our purpose was to assess the efficacy and safety of intravenously administered fish-oil-derived lipid emulsion on chronic plaque-type psoriasis. METHODS: A double-blind, randomized, parallel group study was performed in eight European centers. Eighty-three patients hospitalized for chronic plaque-type psoriasis with a severity score of at least 15 according to the Psoriasis Area and Severity Index (PASI) participated in a 14-day trial. They were randomly allocated to receive daily infusions with either a omega-3 fatty acid-based lipid emulsion (Omegavenous; 200 ml/day with 4.2 gm of both EPA and docosahexaenoic acid (DHA); 43 patients) or a conventional omega-6-lipid emulsion (Lipovenous; EPA+DHA < 0.1 gm/100 ml; 40 patients). The groups were well matched with respect to demographic data and psoriasis-specific medical history. Efficacy of therapy was evaluated by changes in PASI, in an overall assessment of psoriasis by the investigator, and a self-assessment by the patient. In one center neutrophil 4- versus 5-series leukotriene (LT) generation and platelet 2- versus 3- thromboxane generation were investigated and plasma-free fatty acids were determined. RESULTS: The total PASI score decreased by 11.2 +/- 9.8 in the omega-3 group and by 7.5 +/- 8.8 in the omega-6 group (p = 0.048). In addition, the omega-3 group was superior to the omega-6 group with respect to change in severity of psoriasis per body area, change in overall erythema, overall scaling and overall infiltration, as well as change in overall assessment by the investigator and self-assessment by the patient. Response (defined as decrease in total PASI of at least 50% between admission and last value) was seen in 16 of 43 patients (37%) receiving the omega-3 emulsion and 9 of 40 patients (23%) receiving omega-6 fatty acid-based lipid emulsion. No serious side effects were observed. Within the first few days of omega-3 lipid administration, but not in the omega-6 supplemented patients, a manifold increase in plasma-free EPA concentration, neutrophil leukotriene B5 and platelet thromboxane B3 generation occurred. CONCLUSION: Intravenous omega-3-fatty acid administration is effective in the treatment of chronic plaque-type psoriasis. This effect may be related to changes in inflammatory eicosanoid generation.

Adult↗
PubMed2003

Topical application of natural honey, beeswax and olive oil mixture for atopic dermatitis or psoriasis: partially controlled, single-blinded study.

OBJECTIVES: To investigate the effects of honey, olive oil and beeswax mixture on patients with atopic dermatitis (AD) or psoriasis vulgaris (PV). MATERIALS AND METHODS: Twenty-one patients with dermatitis and 18 patients with psoriasis were entered for patient-blinded, partially controlled study; 11 patients with dermatitis used topical betamethasone esters and 10 patients with psoriasis used clobetasol propionate. Honey mixture contained honey, beeswax and olive oil (1:1:1). Mixtures A, B, and C contained honey mixture with the corticosteroids ointment in a ratio of 1:1, 2:1, and 3:1 respectively. Patients with dermatitis were subjected to controlled bilateral half-body comparison to evaluate the efficacy of honey mixture against Vaseline, or mixture A against Vaseline-betamethasone esters mixture (1:1) in patients using topical corticosteroid treatment. In patients with psoriasis, the effect of honey mixture was compared with paraffin in an individual right/left-sites comparison, or mixture A against paraffin-clobetasol propionate mixture (1:1) in patients using corticosteroid topical therapy. In dermatitis, body lesions on right or left half-body were assessed for erythema, scaling, lichenification, excoriation, indurations, oozing and itching on a 0-4 points scale. In psoriasis, lesions of selected site were assessed for redness, scaling, thickening and itching, on a 0-4 points scale. RESULTS: In honey mixture group, 8/10 patients with dermatitis showed significant improvement after 2 weeks, and 5/11 patients pretreated with betamethasone esters showed no deterioration upon 75% reduction of corticosteroid doses with use of mixture C. In psoriasis, 5/8 patients showed a significant response to honey mixture. In patients using clobetasol propionate, 5/10 patients showed no deterioration upon 75% reduction of corticosteroid doses with use of mixture C. CONCLUSION: Honey mixture appears useful in the management of dermatitis and psoriasis vulgaris.

Administration, Topical↗
PubMed2004

Quality of life improvement in treatment of psoriasis with intermittent short course cyclosporin (Neoral).

Due to concern over long term safety of continuous treatment with cyclosporin, the aim of this 1-year study was to assess the effect of intermittent therapy with cyclosporin (Neoral) on the quality of life of patients suffering from chronic plaque psoriasis. A total of 41 patients with chronic plaque psoriasis (26 male, mean age: 36 years, range: 18-61; duration of psoriasis 17 years, range: 2-31) entered a 9-centre open study in which cyclosporin was taken as an initial dose of 5 mg/kg/daily for a maximum of 12 weeks for up to three cycles. Each patient completed a psoriasis specific QOL measure (Psoriasis Disability Index, PDI) at the beginning and end of each treatment cycle and at the end of study. Clinical parameters including Psoriasis Area and Severity Index (PASI) were measured. The PDI scores showed a significant improvement (p < 0.01) between the beginning and end of all three treatment cycles. The various clinical assessments for each treatment period also showed significant improvement (p < 0.001) for all three cycles. When comparing the last follow-up value to baseline there was a clear indication of relapse, but these scores were still significantly better than at baseline (p < 0.01). Notably, the mean PASI score improved by more than 50% (p < 0.001) between first baseline and end of the study. These findings indicate that a short course of intermittent therapy with cyclosporin in microemulsion formulation, used at starting doses of 5 mg/kg/day, improves QOL of patients with chronic plaque psoriasis. Once again, the applicability and validity of the PDI as a useful QOL tool has been demonstrated.

Adolescent↗
PubMed2003

Objective assessment of involved surface area in patients with psoriasis.

BACKGROUND/AIMS: Although difficult, it is essential to assess the disease severity of psoriasis objectively. The visual grading method currently used for assessing the involved surface area in patients with psoriasis, which is included on the Psoriasis Area and Severity Index (PASI) scoring system, is a subjective method. The aim of this study was to establish the reliable objective method, in estimating the involved surface area in patients with psoriasis. METHODS: Thirty patients with psoriasis participated in this study. The skin lesions of each patient were estimated using the visual grading method and an image analysis system. RESULTS: The differences between five dermatologists' estimates of the involved surface area obtained from the visual grading method were highly significant (P<0.05, Kruskal-Wallis test). The comparison between the visual grading method and the image analysis system showed that the involved areas measured by the visual grading method were significantly higher than those from the image analysis (P<0.05, Wilcoxon signed rank test). CONCLUSIONS: The visual grading method was neither objective nor reproducible. On the other hand, the image analysis system can be used as an objective method of measuring the involved surface area of patients with psoriasis. Therefore, the image analysis system can be used as a standard for the assessment of the involved area of patients with psoriasis.

Adult↗
PubMed2003

A putative RUNX1 binding site variant between SLC9A3R1 and NAT9 is associated with susceptibility to psoriasis.

Psoriasis (OMIM 177900) is a chronic inflammatory skin disorder of unknown pathogenesis affecting approximately 2% of the Western population. It occurs more frequently in individuals with human immunodeficiency virus, and 20-30% of individuals with psoriasis have psoriatic arthritis. Psoriasis is associated with HLA class I alleles, and previous linkage analysis by our group identified a second psoriasis locus at 17q24-q25 (PSORS2; ref. 7). Linkage to this locus was confirmed with independent family sets. Additional loci have also been proposed to be associated with psoriasis. Here we describe two peaks of strong association with psoriasis on chromosome 17q25 separated by 6 Mb. Associated single-nucleotide polymorphisms (SNPs) in the proximal peak lie in or near SLC9A3R1 (also called EBP50 and NHERF1) and NAT9, a new member of the N-acetyltransferase family. SLC9A3R1 is a PDZ domain-containing phosphoprotein that associates with members of the ezrin-radixin-moesin family and is implicated in diverse aspects of epithelial membrane biology and immune synapse formation in T cells. The distal peak of association is in RAPTOR (p150 target of rapamycin (TOR)-scaffold protein containing WD-repeats). Expression of SLC9A3R1 is highest in the uppermost stratum Malpighi of psoriatic and normal skin and in inactive versus active T cells. A disease-associated SNP lying between SLC9A3R1 and NAT9 leads to loss of RUNX1 binding. This is the second example of loss of a RUNX1 binding site associated with susceptibility to an autoimmune disease. It also suggests defective regulation of SLC9A3R1 or NAT9 by RUNX1 as a susceptibility factor for psoriasis.

Arylamine N-Acetyltransferase↗
PubMed2003

Induction of graft-versus-autoimmune (GVA) disease effect against refractory psoriasis by complete donor-type chimerism and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

A 67-year-old man with AML, who had a 21-year history of psoriasis without remission, received a reduced-intensity transplantation from an HLA-identical sibling. The preparative regimen consisted of busulfan and fludarabine. Graft-versus-host-disease (GVHD) prophylaxis was cyclosporine and methotrexate. Psoriasis was completely resolved on day 18. The subsequent clinical course was uneventful until day 42, when psoriasis recurred at the same sites as before RIST. Peripheral blood examined on day 63 showed mixed chimerism with 54% recipient type. Cyclosporine was rapidly tapered off over the next 2 weeks. On day 90, 100% donor-type chimerism was confirmed. Subsequently, psoriasis improved simultaneously with the occurrence of mucositis and rash as a manifestation of GVHD. Scattered erythematous patches of psoriasis disappeared again by day 105. We initiated 0.5 mg/kg prednisolone on day 119, and resumed cyclosporine on day 133. At 7 months after RIST, he still suffers from chronic GVHD, but his psoriasis remains in remission for the first time in 21 years. The anti-psoriasis effect of the conditioning is mild and transient, while the graft-versus-autoimmunity effect, related to the induction of complete donor-type chimerism and GVHD, is more profound and persisting. A graft-versus-autoimmunity effect lies in the delicate balance between alloimmunity and immunosuppressant used for GVHD prophylaxis/treatment.

Aged↗
PubMed2006

Interaction between genetic control of vascular endothelial growth factor production and retinoid responsiveness in psoriasis.

Vascular endothelial growth factor (VEGF) promotes angiogenesis, and elevated levels are found in plaques of psoriasis. Two VEGF polymorphisms, +405 and -460, are associated with early-onset psoriasis and are close to the functional activator protein-1 site (+419) through which retinoids, an established systemic therapy for psoriasis, can block production of VEGF. We report that peripheral blood mononuclear cells (PBMCs) and epidermal keratinocytes (KC) from patients with psoriasis demonstrate differential, genotype-dependent, regulation of VEGF. For PBMCs, VEGF genotype distinguishes two groups of patients with psoriasis - "high and low VEGF producers" (P < 0.001). In contrast, KC production of VEGF is not genotype dependent. However, the effects of all-trans retinoic acid (RA) on cellular expression of VEGF are determined by both cell type and genotype. RA inhibits KC production of VEGF in a genotype-dependent manner (P < 0.005) whereas RA stimulates PBMCs production irrespective of VEGF genotype (P < 0.001). We also report that the -460 VEGF polymorphism appears to have a clinical pharmacogenetic role in predicting response or non-response of psoriasis to acitretin (P = 0.01). In future, determination of VEGF gene polymorphisms and thus individual patient VEGF "signatures" may be used as a prognostic factor for psoriasis susceptibility/severity and as a means for optimizing treatment response.

Acitretin↗
PubMed2004

Single-nucleotide polymorphisms of vascular endothelial growth factor in psoriasis of early onset.

Vascular endothelial growth factor (VEGF)--a stimulus of angiogenesis--is produced by epidermal keratinocytes, and elevated levels have been found in plaques of psoriasis. Polymorphisms in the VEGF gene regulate production of VEGF. We postulated that patients with psoriasis may have altered systemic expression of VEGF consequent upon programming at the genomic level. We investigated the genetic basis of VEGF expression in patients with type 1 (onset before age 40 y) chronic plaque psoriasis compared to healthy controls and also measured plasma levels of VEGF and its receptors flt-1 and KDR. Patients with severe disease, and those with onset of psoriasis between the ages of 20 and 40 y showed significantly increased frequency of the +405 CC genotype (p=0.04 and p=0.02) and the C allele (p=0.03 and p=0.02), respectively, compared to healthy controls. Plasma levels of VEGF and flt-1 were significantly detectable in patients with psoriasis compared with controls (p<0.001); by contrast, mean plasma levels of KDR in psoriatic patients were comparable with controls. These results suggest that alterations in the biology of VEGF may be involved in the pathogenesis of psoriasis. VEGF, flt-1, and KDR could provide attractive targets for future psoriasis therapy.

Adolescent↗
PubMed1999

Levels of endothelial cell stimulating angiogenesis factor and vascular endothelial growth factor are elevated in psoriasis.

Neovascularization appears to play an early and important part in the evolution of psoriatic plaques. We studied the distribution and production of two known angiogenesis factors, endothelial cell stimulating angiogenesis factor (ESAF) and vascular endothelial growth factor (VEGF), in the skin of patients with chronic plaque psoriasis and normal control subjects. Our results showed that tissue levels of ESAF and VEGF were significantly elevated in involved as compared with normal control skin (P = 0.006 and P < 0. 0001, respectively). Tissue levels of ESAF and VEGF were also raised in involved skin as compared with uninvolved skin in patients with psoriasis (P = 0.001 and P < 0.0001, respectively). Tissue levels of ESAF and VEGF in plaques of psoriasis correlated closely with the clinical severity of psoriasis (r = 0.6 and r = 0.9, respectively). Serum levels of ESAF and VEGF were significantly raised in patients with psoriasis as compared with control subjects (P = 0.001 and P = 0.02, respectively). In vitro culture studies revealed that ESAF is produced by both keratinocytes and fibroblasts in approximately equal quantities in normal skin, whereas VEGF is secreted predominately by keratinocytes. A similar pattern is seen in both involved and uninvolved skin of patients with psoriasis. However, there is increased secretion of both factors in keratinocytes and fibroblasts from involved and uninvolved skin as compared with normal control skin (P < 0.001). The increased levels and secretion in plaques of psoriasis of two molecules, ESAF and VEGF, known to promote new blood vessel formation, suggest a pathogenetic role for them in this disease.

Adult↗
PubMed2000

A controlled study of ultraviolet A sunbed treatment of psoriasis.

BACKGROUND: Ultraviolet (UV) A sunbeds are widely used by patients with psoriasis in an attempt to treat their skin disease. However, there is little evidence that UVA therapy improves psoriasis, and the long-term risks of sunbed exposure are not known. OBJECTIVES: To perform a randomized, placebo-controlled study of UVA sunbed therapy for psoriasis. METHODS: A sunbed and canopy unit was modified to allow UVA exposure on one side of the body (front and back), and 'placebo' visible light exposure on the other side of the body. We treated 38 patients with psoriasis, giving 12 exposures over a period of 4 weeks. Assessment was made using a modified Psoriasis Area and Severity Index (PASI) score, individual plaque assessment and patient questionnaire. RESULTS: In 17 patients (47%) the PASI score showed a greater reduction on the UVA side compared with placebo, in 11 patients (31%) no difference was recorded between the two sides, and in eight (22%) the improvement was greater on the placebo-treated side. Overall, the median pretreatment half-body modified PASI score was 4.4 units, reducing to 3.9 units on the UVA-treated side and 4.2 units on the placebo-treated side (P = 0. 044 for difference in response). Breakdown of the plaque score into the individual components of erythema, scale and thickness revealed significant improvement only with the score for erythema. Although the degree of improvement was small, 64% of patients felt that the response was sufficiently good that they would use a sunbed again to treat their psoriasis. CONCLUSIONS: Our results show that a short course of sunbed treatment does improve psoriasis in some patients, but that the degree of improvement is small.

Adult↗
PubMed2001

Social coping strategies associated with quality of life decrements among psoriasis patients.

BACKGROUND: Individuals with psoriasis often report significant psychological distress, physical disability, social strain and reduced quality of life. Little is known about how they cope with the illness. OBJECTIVE: The primary aim of this study is to determine whether patients' efforts to cope with psoriasis are associated with better or worse health-related quality of life (HRQL). METHODS: Focus groups identified seven commonly used coping strategies that were subsequently measured, along with HRQL and other variables, in a survey of 318 individuals with psoriasis. RESULTS: Results revealed: (i) that psoriasis is associated with decrements in all quality of life domains that were assessed, and (ii) that commonly used coping strategies such as telling others about psoriasis, covering the lesions and avoiding people were associated with greater decrements in HRQL after controlling for covariates; however, telling others that psoriasis is not contagious was associated with smaller HRQL decreases. CONCLUSIONS: How patients cope with the social aspects of psoriasis is associated with their quality of life.

Adaptation, Psychological↗
PubMed2002

Downregulation and altered spatial pattern of caveolin-1 in chronic plaque psoriasis.

BACKGROUND: Caveolin-1 is a key structural and functional protein for plasmalemmal invaginations termed caveolae. Caveolin-1 is known to modulate multiple signal-transducing pathways involved in cell differentiation and proliferation. Psoriasis is viewed as a multifactorial pathology characterized by keratinocyte hyperproliferation and abnormal cell maturation. We hypothesized that loss of caveolin-1 within epidermal keratinocytes may contribute to the development and/or progression of the psoriatic phenotype. OBJECTIVES: To examine the expression and spatial distribution of caveolin-1 in skin biopsies from normal subjects and in patients with psoriasis. METHODS: Using immunohistochemical methods caveolin-1 protein expression was assayed in two independent patient groups. Firstly, a retrospective analysis was conducted on archival skin samples obtained from nine normal subjects and from involved tissue of 12 patients with psoriasis. Following this, a prospectively designed study was conducted in 10 further patients with active psoriasis and involving caveolin-1 staining of biopsy tissue from the uninvolved, advancing edge and lesional skin tissue from within the same subject. RESULTS: In normal skin or uninvolved skin from psoriasis patients intense caveolin-1 staining was present throughout full-thickness epidermis. In 20 of the 22 patient cases (combined retrospective and prospective samples) caveolin-1 protein was significantly reduced and consistently showed very weak or absent staining within the hyperproliferative basal cell layers of the psoriatic plaque (P < 0.002 for retrospective archival study and P < 0.01 for prospectively designed study). Comparisons between caveolin-1 staining in uninvolved tissue and at the advancing edge of a migrating plaque were more equivocal (P > 0.05). CONCLUSIONS: The findings of this study are consistent with a downregulation of caveolin-1 that may serve as an aetiological factor in the development and/or progression of psoriasis. Further mechanistic investigations are required with the potential that caveolin-1 protein may be a novel target for therapy of psoriasis.

Adolescent↗
PubMed2003

Interleukin-10 promoter polymorphism IL10.G and familial early onset psoriasis.

BACKGROUND: The anti-inflammatory cytokine interleukin (IL)-10 is considered to play a major role in the pathophysiology of psoriasis, which is characterized by an IL-10 deficiency. Systemic administration of IL-10 has been shown to be an effective therapy for psoriasis. The IL-10 promoter region contains a highly polymorphic microsatellite (IL10.G) and in a recent case-control study the IL10.G13 (144 bp) allele was found to be associated with familial early onset psoriasis (type 1 psoriasis) having a susceptible effect. OBJECTIVES: As it is essential in multifactorial diseases to replicate findings before definite conclusions can be drawn, we decided to perform a follow-up study and to follow a genetic approach analysing allele transmission in families with a positive family history of psoriasis. METHODS: We studied 137 nuclear families (trio-design) comprising 456 individuals and genotyped the IL10.G marker. For comparison we also genotyped the microsatellite tn62 as a reference marker of the major psoriasis susceptibility locus on chromosome 6p21 (PSORS1). In the present study allele transmission was evaluated using the family-based association test (FBAT) and GENEHUNTER 2.0 based on the transmission/disequilibrium test. RESULTS: The G13 allele (144 bp) had a frequency of 24%, was present in 88 families and clearly showed an even transmission (FBAT, P = 0.753). In contrast, allele 3 (IL10.G9) (136 bp) had a frequency of 39%, was present in 110 families and was transmitted in 43 trios and remained untransmitted in 67 trios (FBAT, P = 0.026), thus showing preferential nontransmission. For the HLA-linked tn62-marker we obtained a P-value of 0.00027 for allele 4 in the same study group. CONCLUSIONS: In conclusion, we failed to confirm the susceptible effect of the G13 allele, but provide the first data for a protective effect of allele 3 (IL10.G9) for familial psoriasis. Our results suggest that the IL10.G polymorphism is not a major locus, but acts as a minor locus.

Alleles↗
PubMed2003

Topical PTH (1-34) is a novel, safe and effective treatment for psoriasis: a randomized self-controlled trial and an open trial.

BACKGROUND: There continues to be a need to develop new pharmacological approaches for treating the common skin disease psoriasis. Human skin produces parathyroid hormone related peptide. This peptide is a potent inhibitor of epidermal cell growth. OBJECTIVES: A programme was initiated to determine whether an agonist of this peptide's receptor, PTH (1-34), could be developed as a drug to treat psoriasis. METHODS: PTH (1-34) was formulated in Novasome A cream. Fifteen adult patients with chronic plaque psoriasis who had failed to respond to at least one standard treatment were enrolled in a randomized double-blinded placebo self-controlled trial. The patients topically applied to a 25-cm2 psoriatic lesion 0.1 g of either Novasome A cream or Novasome A cream that contained 20 microg of PTH (1-34) twice a day for 2 months. At the end of the double-blind study, patients were enrolled in an open large area study. Ten patients applied PTH (1-34) (50 microg per 0.1 g) once daily to their psoriatic lesions. The patients were evaluated for their global improvement and calcium metabolism. RESULTS: Novasome A cream enhanced the percutaneous absorption of PTH (1-34) in human skin in comparison with formulations in propylene glycol or normal saline. Psoriatic lesions treated with PTH (1-34) showed marked improvement in scaling, erythema and induration. There was a 67.3% improvement in the global severity score for the lesion treated with PTH (1-34) compared with the placebo-treated lesion, which only showed a 17.8% improvement. Ten patients topically applied PTH (1-34) on all of their lesions in a stepwise manner. A Psoriasis Area and Severity Index score analysis of all the patients revealed improvement of 42.6% (P < 0.02). None of the patients experienced hypercalcaemia or hypercalciuria or developed any side-effect to the medication. CONCLUSIONS: Patients who were resistant to at least one standard therapy for psoriasis had a remarkable improvement in their psoriasis when they applied PTH (1-34) to their lesion(s). No untoward toxicity was observed in any of the subjects. This pilot study suggests that topical PTH (1-34) is a safe and effective novel therapy for psoriasis.

Administration, Cutaneous↗