Psoriasis Vulgaris Patients Research Articles

Methylenetetrahydrofolate Reductase C677T Gene Polymorphism as Risk Factor for Psoriasis in Saudis.

Methylenetetrahydrofolate reductase (MTHFR) has been linked with the etiopathogenesis of psoriasis with inconsistent results. Methylenetetrahydrofolate reductase C677T polymorphism was evaluated in 106 Saudi psoriasis vulgaris patients and 280 matched healthy controls using PCR-RFLP (restriction fragment length plymorphism) technique. The cardiovascular risk factors were also compared in cases and controls. Allele T and genotypes CT and TT were found to be increased while allele C and genotype CC significantly decreased in psoriasis patients as compared with controls (P < .001). These results showed that the T-allele and T-containing genotypes (TT, CT) of MTHFR C677T are significantly linked with psoriasis susceptibility while C-allele and CC genotype are protective for it. Body mass index, fasting glucose, total cholesterol, low-density lipoprotein, triglycerides, and C-reactive protein, known markers for cardiovascular diseases, were found to be significantly elevated in the patient group as compared with the controls. It is concluded that the MTHFR C677T polymorphism increases psoriasis risk in Saudi patients.

Assessment of the Possible Role of FOXP3 Gene (rs3761548) Polymorphism in Psoriasis Vulgaris Susceptibility and Pathogenesis: Egyptian Study.

Background:Psoriasis is an autoimmune-related chronic inflammatory skin disorder. Psoriasis vulgaris (PV) is the most common form of psoriasis. T regulatory cells (Tregs) are typically considered inhibitors of autoimmune responses. FOXP3 is a master control transcription factor for development and function of Tregs. FOXP3 gene polymorphism changes FOXP3 protein function and quantity leading to Tregs dysfunction that subsequently may be related to PV pathogenesis.Objective:The objective of the present study was to evaluate the possible role of FOXP3 gene (rs3761548) polymorphism in PV pathogenesis.Materials and Methods:One hundred sixty subjects were included in the present study (80 PV patients and 80 well-matched healthy controls). All participants were evaluated by detailed history, general examination, dermatological examination, and psoriasis area and severity index (PASI) score. The detection of FOXP3 gene (rs3761548) polymorphism in patients and controls by PCR-restriction fragment length polymorphism technique was done.Results:There was statistically significant increase in CC genotype and C allele in patients compared to controls, whereas there were non-significant differences in AA and AC genotypes. However, there were non-significant associations between genotype distribution and each of age, sex, family history, PASI score, hair affection, nail affection, hypertension, diabetes mellitus, and body mass index.Conclusion:FOXP3 gene (rs3761548) polymorphism may increase susceptibility of PV and share in its pathogenesis as it leads to changes in FOXP3 protein function and quantity that subsequently affect T-regs functions. Further investigations for the role of other FOXP3 genes polymorphisms in psoriasis pathogenesis and their effects on the treatment response in psoriasis patients are strongly recommended.

IL-36 receptor antagonistic antibodies inhibit inflammatory responses in preclinical models of psoriasiform dermatitis.

Psoriasis vulgaris (PV) results from activation of IL-23/Th17 immune pathway and is further amplified by cytokines/chemokines from skin cells. Among skin-derived pro-inflammatory cytokines, IL-36 family members are highly upregulated in PV patients and play a critical role in general pustular psoriasis. However, there is limited data showing crosstalk between the IL-23 and IL-36 pathways in PV. Herein, potential attenuation of skin inflammation in the IL-23-induced mouse model of psoriasiform dermatitis by functional inhibition of IL-36 receptor (IL-36R) was interrogated. Anti-mouse IL-36R monoclonal antibodies (mAbs) were generated and validated in vitro by inhibiting IL-36α-induced secretion of CXCL1 from NIH 3T3 cells. Antibody target engagement was demonstrated by inhibition of CXCL1 production in a novel acute model of IL-36α systemic injection in mice. In addition, anti-IL-36R mAbs inhibited tissue inflammation and inflammatory gene expression in an IL-36α ear injection model of psoriasiform dermatitis demonstrating engagement of the target in the ear skin. To elucidate the possible role of IL-36 signalling in IL-23/Th17 pathway, the ability of anti-IL-36R mAbs to inhibit skin inflammation in an IL-23 ear injection model was assessed. Inhibiting the IL-36 pathway resulted in significant attenuation of skin thickening and psoriasis-relevant gene expression. Taken together, these data suggest a role for IL-36 signalling in the IL-23/Th17 signalling axis in PV.

Immunoregulatory Effect of Adipose Mesenchymal Stem Cells on Peripheral Blood Lymphocytes in Psoriasis Vulgaris Patients

Objective To investigate the effect of adipose mesenchymal stem cells(AMSCs) on the peripheral blood lymphocyte(PBL) in psoriasis vulgaris(PV) patients and the expression and secretion profiles of related inflammatory cytokines in the PBL.Methods AMSCs from three PV patients were co-cultured with PBL. Peripheral blood regulatory cells(Treg) and T helper cell 17(Th17)ratio was measured by flow cytometry. The anti- and pro-inflammatory cytokines expressed and secreted by PBL were detected by quantitative real-time polymerase chain reaction(qRT-PCR) and enzyme-linked immunosorbent assay(ELISA).Results The Treg/total lymphocyte ratio was significantly higher in the healthy people AMSCs+PBL co-culture group[(3.2±0.5)%;P=0.001],but AMSCs in patients had a tendency to promote the proliferation of Treg cells [(1.3±0.2)%],with no significant difference(P=0.485) when compared with the PBL culture alone group[(1.0±0.1)%]. qRT-PCR showed that the ability of PBL in expressing Treg transcription factor forkhead box p3 and transforming growth factor(TGF)-Β mRNA was significantly lower in psoriasis AMSCs+PBL co-culture group than in the healthy people AMSCs+PBL co-culture group(P=0.00,P=0.03),AMSCs had a tendency to promote the expression of interlukin(IL)-10 in peripheral blood lymphocytes,but there was no significant difference(P=0.09).ELISA showed the PBL in healthy people AMSCs+PBL co-culture group secreted the anti-inflammatory cytokine IL-10[(156.9±41.8) ng/Μl] and TGF-Β[(2774.1 ± 526.4) ng/Μl];in contrast,the abilities of PBL in PV patient AMSCs+PBL co-culture group in secreting the anti-inflammatory cytokines has a downward trend:IL-10[(90.4±28.8) ng/Μl] and TGF-Β[(1597.9±55.7) ng/Μl],although the differences were not statistically significant. After the co-culture,the proportion of Th17 cells in the psoriasis AMSCs+PBL co-culture group[(0.8±0.3)%] showed a decreasing trend when compared with the PBL culture alone group[(1.1±0.1)%],although the results were not statistically significant. Also,the proportion of Th17 cells showed no significant difference between PV patient AMSCs+PBL co-culture group and healthy people AMSCs+PBL co-culture group. Finally,both the psoriasis AMSCs+PBL co-culture group and the healthy people AMSCs+PBL co-culture group showed no obvious inhibitory effect on the expression and secretion of Th17 transcription factor retinoid-related orphan nuclear receptor Γt and pro-inflammatory cytokines IL-17 and IL-23 in PBL,and there was no significant difference between these two groups.Conclusions AMSCs in PV patients have decreased ability in regulating the anti-inflammatory function of peripheral blood Treg lymphocytes. However,they have no effect on the proinflammatory effect of peripheral blood Th17 lymphocytes.

Subclinical atherosclerosis in psoriatic disease: relation to endocan, TNF‐α, age of onset, and body fat

Psoriasis is a common multisystem inflammatory disease with several associated comorbidities. Serological markers to detect associated subclinical atherosclerosis in psoriatic patients are needed. We aimed to study serum endocan levels in psoriasis vulgaris and its relation to severity of psoriasis, systemic inflammation, associated atherosclerosis, obesity, and the possible factors affecting its level in psoriatic patients. This study was conducted on 30 moderate-severe psoriasis vulgaris patients and 30 healthy controls. Body mass index, body fat percent, and PASI assessments were done. Serum endocan and tumor necrosis factor-α levels were measured by ELISA. Carotid artery intima-media thickness measurement by high-resolution ultrasound was performed. Psoriasis patients showed significantly higher serum tumor necrosis factor-α and endocan levels (P1 = 0.008, P2 = 0.003). Additionally, there was a statistically significant difference between mean carotid artery intima-media thickness of both groups (P = 0.005). Serum endocan levels positively correlated with PASI score (P = 0.002), tumor necrosis factor-α levels (P < 0.001), mean carotid artery intima-media thickness (P = 0.001), and body mass index (P < 0.001) in the patients group. Additionally, the age of onset of disease negatively correlated with serum endocan (P = 0.003). Serum endocan is a promising marker of severity of psoriasis and associated atherosclerosis. Early onset psoriasis is associated with higher serum endocan levels. Body mass index is positively correlated with serum endocan levels. The positive correlation of endocan and tumor necrosis factor-α supports the regulatory effect of the cytokine on endocan production and suggests the role of endocan as an inflammatory marker.

Lesional upregulation of SLURP1 immunostaining parallels disease severity in psoriasis vulgaris patients.

The exact pathogenesis of psoriasis is still unclear. SLURP1 is vital for the normal differentiation of keratinocytes, and could therefore be involved in psoriasis. In this study we investigated the immunohistochemical staining reaction of SLURP1 in psoriasis vulgaris patients and its possible relation to disease pathogenesis. 20 patients with psoriasis vulgaris, 20 patients with psoriasiform dermatitis and 20 normal skin samples were studied. Psoriasis severity was measured with a combination of PASI and DLQI scores. Lesional and non-lesional sites were biopsied for each psoriasis patient. A single biopsy sample was taken for cases with psoriasiform dermatitis and for controls. All sections were immunostained for SLURP1 according to the manufacturer's protocol. Significant differences were noted in SLURP1 immunostaining between lesional and non-lesional biopsies of psoriasis patients and between lesional biopsies of psoriasis patients and lesional sites of psoriasiform dermatitis. However, the differences between non-lesional biopsies of psoriasis patients and normal controls were not significant. Furthermore, the grading of SLURP1 immunostaining paralleled the degree of psoriasis severity. SLURP1 immunostaining is significantly increased in lesional skin of psoriasis vulgaris and not in psoriasiform dermatitis, which demonstrates the role of SLURP1 in the pathogenesis of psoriasis. SLURP1 could be used as a biological marker for psoriasis severity, and this hypothesis warrants further investigation.

Local production of prolactin in lesions may play a pathogenic role in psoriatic patients and imiquimod-induced psoriasis-like mouse model.

Human prolactin (PRL) is a well-known hormone for pituitary of lactation and reproduction, but it also has immunostimulatory effect in some inflammatory or autoimmune diseases including psoriasis, which has not been well elucidated. This study aimed to determine the relationship between PRL and psoriasis through clinical case-control studies, and explore the function of PRL in the pathogenesis of imiquimod (IMQ)-induced psoriasis-like mouse model. Serum from patients with psoriasis vulgaris (PsV), patients with erythrodermic psoriasis, and healthy controls (HCs) were collected for PRL test. Skin biopsies were collected for PRL, PRL receptors (PRLRs), cytokines mRNA level determination, PRL immunohistochemistry and PRL Western blotting. Mice were divided into four groups (each n=6): control group (CON), IMQ group, anti-PRL group and solvent group. Anti-PRL group and solvent group mice were treated with PRL antagonist (cabergoline) and the solvent (0.25% methylcellulose) separately. The serum PRL level of PsV patients was significantly higher than that of HCs (P<0.001). Compared with HCs, the mRNA levels of PRL and Th1/Th17 cytokines in skin lesions increased significantly (P<0.05), and the PRL protein level was also significantly elevated in the epidermis and dermis of PsV patients. In IMQ-induced psoriasis-like mouse model, the mRNA and protein levels of PRL in skin lesions were significantly higher than CON group (P<0.01). Comparing to solvent group, serum PRL level and PRL, cytokines mRNA levels in skin lesions all decreased significantly and the skin inflammatory condition was also alleviated obviously in anti-PRL group. This study suggests that local production of PRL is the main resource of PRL in skin lesions and may play an important role in skin inflammatory of psoriasis.

Polymorphisms of SLCO1B1 rs4149056 and SLC22A1 rs2282143 are associated with responsiveness to acitretin in psoriasis patients

Acitretin is widely used to treat psoriasis, but the efficacy varies significantly among individuals. To explore the association between polymorphisms and acitretin efficacy, we enrolled 46 and 105 Chinese Han psoriasis vulgaris patients for discovery and validation phases, respectively. The patients were treated with acitretin (30 mg/day) and calcipotriol ointment for at least 8 weeks, and their genotypes were detected. The wild-type genes and variants were transfected into HEK293 cells, which were then incubated with acitretin. The cellular acitretin concentration was measured by liquid chromatography-mass spectrometry. We found that the polymorphisms rs4149056 in the SLCO1B1 gene and rs2282143 in the SLC22A1 gene were associated with efficacy, both in the discovery (P = 0.013 and P = 0.002) and validation phases (P = 0.028 and P = 0.014), based on a 50% reduction from before to after treatment of the psoriasis area severity index (PASI50). When the PASI75 was used as an efficacy cutoff, a similar conclusion was drawn. The uptake of acitretin was lower with the rs4149056C (P = 0.002) and rs2282143T alleles (P = 0.038) than the wild-type alleles. Our results imply that the rs4149056C and rs2282143T variants decrease the acitretin uptake, and significantly associated with clinical effective responsiveness.

Effect of methotrexate on regulation for the number of regulatory T cells and expression of Foxp3 in psoriasis

To explore the role of methotrexate (MTX) in regulating the number of regulatory T cells (Treg) and the mRNA expression of transcription factor Foxp3. Methods: 1) We analyzed the number of Treg and the mRNA expression of Foxp3 by flow cytometry (FCM) and quantitative real-time PCR (qRT-PCR) respectively in patients with psoriasis vulgaris, patients with psoriasis vulgaris after the 8-week treatment of MTX, and healthy people. 2) BALB/c female mice were smeared with imiquimod (IMQ) cream for 6 days. We recorded the change of the lesion in mice every day. The morphological changes of lesion in mice were evaluated by the psoriasis area and severity index (PASI) and HE staining. 3) The mouse model was randomly divided into a control group and an MTX group. The MTX group was treated with different doses of MTX (38.5 and 77.0 nmol/L) on the third day of this experiment. The morphological changes of lesion in mice were evaluated by PASI and HE staining. We tested the number of Treg and the expression level of Foxp3 mRNA in splenic lymphocytes. Results: 1) The number of Treg and the expression level of Foxp3 mRNA were lower in psoriasis vulgaris patients than those in the healthy control group (P<0.05). After 8-week treatment of MTX, the number of Treg was increased (P<0.05) and Foxp3 mRNA level was up-regulated (P<0.01). 2) Typical psoriasis-like skin lesions, such as red scaly skin plaque were found after topical application of IMQ. Both the number of Treg in the splenic lymphocytes of mice and the Foxp3 mRNA level of Treg were reduced by IMQ (P<0.01 and P<0.05). 3) Different doses of MTX for mice showed the ability to improve skin lesion, increase the number of Treg in the spleen of mice and Foxp3 mRNA level in psoriatic dermatitis of mice (P<0.05). Conclusion: MTX is able to regulate the number of Treg and Foxp3 mRNA expression in psoriasis.

Genetic polymorphism of IL36RN in Han patients with generalized pustular psoriasis in Sichuan region of China: A case-control study.

The aim of this study was to detect IL36RN variant types and frequency in Han patients with generalized pustular psoriasis (GPP) in Sichuan region of China, reveal the difference of variant frequency between GPP alone and GPP + PV (psoriasis vulgaris), and preliminarily clarify the pathogenesis of GPP in this region.Genomic DNA was extracted and subjected to polymerase chain reaction (PCR) for the amplification of the entire encoding and splice sites of the IL36RN gene followed by bidirectional sequencing. Differences in frequencies of IL36RN variants between groups were analyzed by SPSS Statistics 17.0 software. Meanwhile, the IL36RN variant frequency between GPP alone and GPP + PV was compared.The total IL36RN variant frequency was 60.47% in Han GPP patients from Sichuan region of China. Three variant types (c.115 + 6T > C, c.140A > G, c.227C > T) were identified, among which c.115 + 6T > C exhibited the highest frequency (55.81%). All the 3 variants’ frequency of GPP alone group had statistical significance when compared with PV patients and normal controls (P < .05). The IL36RN variant frequency of GPP alone group was statistically higher than that of GPP + PV group (79.17% vs 36.84%, P < .05).IL36RN may be the major disease-causing gene in GPP patients in Han population in Sichuan region of China. c.115 + 6T > C is a possible hot-spot mutation within the IL36RN gene. In contrast to GPP + PV, IL36RN mutations possibly play a more important role in the development of GPP alone.

Genetic polymorphism predicting Methotrexate efficacy in Chinese patients with psoriasis vulgaris

BackgroundMethotrexate is the first systemic therapeutics of psoriasis. It is reported that 40% of the patients achieved a PASI75 after 12 weeks with a small dose of methotrexate (15mg / w) treatment. So far there is not any large-scale exome sequencing been used to predict the efficacy of methotrexate in the treatment of psoriasis vulgaris. ObjectiveTo analyze the genetic polymorphism to predict methotrexate efficacy in Chinese patients with psoriasis vulgaris. MethodsIn this study, we used the whole exon high-throughput sequencing technology to detect the DNA sequence of 22 psoriasis vulgaris patients (11 responders, 11 non-responders) treated with methotrexate and captured approximately 236 variants with statistically significant in the whole exon sequencing, then in accordance with statistical differences and clinical relevance, we further selected 36 SNPs and 14 SNPs that have been reported in articles associated with the response of methotrexate. We used MassARRAY method to verify the 50 SNPs in 100 psoriatic patients treated with methotrexate. ResultsWe found 3 SNPs, rs216195T>C in SMG6, rs1050301G>A in IMMT, rs2285421T>C in UPK1A which might associate with the drug response of methotrexate. ConclusionWe have searched 3 new SNPs that could predict the efficacy of methotrexate in psoriasis vulgaris to some extent, providing a theoretical basis for precision medicine of methotrexate in future.

NAT2 Gene Polymorphisms in Turkish Patients with Psoriasis Vulgaris.

Psoriasis is a common, chronic, and autoimmune skin disease. Factors that play a role in etiopathogenesis of psoriasis include internal factors such as genetic susceptibility and immunological factors and external factors such as stress, infection, trauma, drug, and environmental compounds. N-acetyltransferase 2 (NAT2) is a xenobiotic enzyme that is involved in the metabolism of drugs, environmental toxins, and carcinogens. In this study, we aimed to demonstrate whether the variations in the NAT2 gene lead to a predisposition to psoriasis by affecting the enzyme's ability to metabolize drugs and environmental components or not. Three polymorphisms (rs1799929, rs1799930, and rs1799931) in NAT2 gene were genotyped and compared by real-time PCR method in 260 psoriasis vulgaris patients and 200 healthy controls. There was no difference in the genotype distributions and allele frequencies of polymorphisms between psoriasis vulgaris patients and controls. When the effects of polymorphisms on the clinical features of the disease, such as onset age and severity, are assessed, it has been found that rs1799930 and rs1799929 are, respectively, associated with early onset age and severity of the disease. In conclusion, rs1799929, rs1799930, and rs1799931 polymorphisms of the NAT-2 gene do not appear to be a risk factor for the development of psoriasis. Conversely, they may have an effect on either more severe or early onset cases of the disease.

Mutational analysis of epidermal and hyperproliferative type I keratins in mild and moderate psoriasis vulgaris patients: a possible role in the pathogenesis of psoriasis along with disease severity

BackgroundMutations in keratin proteins have been vastly associated with a wide array of genodermatoses; however, mutations of keratins in psoriasis have not been fully investigated. The main aim of the current research was to identify the mutation in K14, K10, K16, and K17 genes in two stages of psoriasis patients.MethodsNinety-six psoriatic skin biopsies were collected. mRNA transcript of K14, K10, K16, and K17 was prepared, amplified, and sequenced. Sanger sequences of all keratins were further validated for mutational analysis using Mutation Surveyor and Alamut Visual. Then, in silico analysis of protein stability and protein and gene expression of all keratins was performed and validated.ResultsOut of 44 mutations, about 75% of keratins are highly pathogenic and deleterious. Remaining 25% mutations are less pathogenic and tolerated in nature. In these 33 deleterious mutations were immensely found to decrease keratin protein stability. We also found a correlation between keratin and Psoriasis Area and Severity Index score which added that alteration in keratin gene in skin causes severity of psoriasis.ConclusionsWe strongly concluded that acanthosis and abnormal terminal differentiation was mainly due to the mutation in epidermal keratins. In turn, disease severity and relapsing of psoriasis are mainly due to the mutation of hyperproliferative keratins. These novel keratin mutations in psoriatic epidermis might be one of the causative factors for psoriasis.

THE DIFFERENCES OF DEPRESSIVE SYMPTOMS BY GENDER IN PEOPLE WITH PSORIASIS

Objectives: The objectives of the study were to determine the differences of depressive symptoms by gender in people with psoriasis.Methods: This study was a comparative analytical study with cross-sectional approach, the sampling techniques using non-probability sampling with consecutive sampling techniques types. Place of study: Psoriasis foundation Medan research time: January 2014–March 2014. Every patient who meets the criteria of psoriasis vulgaris patients aged 16–60 years, disease duration &gt;6 months, able to read and write, cooperative and willing to participate in the study, did not suffer severe medical illness, did not suffer from other mental disorders, and not using illicit substances included in the study, and then, to assess depressive symptoms using a questionnaire beck depression inventory-II.Results: A total of 80 patients were evenly split into groups of men and women have the highest life characteristics at 16–38 years (55% and 72.5%). Highest education in higher education both 95% and the severity of depressive symptoms was also a lot of artifacts on minimal depressive symptoms (82.5% and 72.5%). Cross-table test showed no significant difference in depressive symptoms between male and women (p&gt;0.05).Conclusion: Overall in people with psoriasis there was no significant difference of depressive symptoms by gender for the entire data.

High-Fat Diet Exacerbates Early Psoriatic Skin Inflammation Independent of Obesity: Saturated Fatty Acids as Key Players

In obesity, hypertrophic adipocytes secrete high amounts of adipocytokines, resulting in low-grade inflammation amplified by infiltrating proinflammatory macrophages, oxidative stress, hypoxia, and lipolysis. These chronic proinflammatory conditions support the development of type II diabetes and cardiovascular diseases, but the mechanisms of obesity-related exacerbation of inflammatory skin disorders like psoriasis are unclear. In this study, we uncovered dietary saturated fatty acids (SFAs) as major risk factors for the amplification of skin inflammation, independent of obesity-related parameters such as fat mass extension, adipocytokine levels, and glucose homeostasis. Correlation analyses in a cohort of psoriasis vulgaris patients showed that free fatty acid serum level was the only obesity-associated parameter affecting disease severity. Studies in mice with high-fat diet-induced obesity with psoriasiform inflammation confirmed this critical role of free fatty acids. An increase of free fatty acids in healthy, lean mice alone was sufficient to induce an exacerbation of psoriasiform inflammation. In particular, saturated fatty acids sensitize myeloid cells to an increased inflammatory response in answer to proinflammatory stimuli, which in turn augments the activation of keratinocytes. Consequently, reduction of nutritional saturated fatty acids alone diminished the psoriatic phenotype in obese mice. Thus, our findings may open new perspectives for adjuvant dietary measures accompanying anti-inflammatory psoriasis therapies in lean and obese patients.

Association of IL36RN mutations with clinical features, therapeutic response to acitretin, and frequency of recurrence in patients with generalized pustular psoriasis.

Previous studies have revealed that IL36RN mutations play a pivotal role in the pathogenesis of generalized pustular psoriasis (GPP), however, the clinical relevance is unclear. To investigate the correlation between IL36RN mutations and clinical features, recurrence frequency, and therapeutic response to acitretin in GPP patients with long-term follow-up. This retrospective cohort study, lasting 2-4 years, included 61 GPP and 48 psoriasis vulgaris (PV) patients. Sequence analysis of all five exons of the IL36RN gene revealed two genetic variants (c.115+6 T>C and c.227C>T). The cohort was divided into three subgroups according to the c.115+6 T>C mutation (present in 52.5% of the patients): homozygous mutation group (HOMG), heterozygous mutation group (HEMG), and non-mutation group (NMG). Initially, 21/25 HOMG patients were diagnosed with GPP with provocative factors, but 13 developed erythrodermic psoriasis after the pustular phase. Patients in the HEMG (5/7) and NMG (23/29) maintained PV diagnosis before and after the pustular phase. Most patients exhibited a marked response to acitretin, but patients who were prescribed a maintenance dosage (10-30mg/d) had mild recurrence (0-2 times/year) during follow-up. IL36RN mutations were strongly linked with early onset and hyponychial pustules, but not with therapeutic efficacy of acitretin or recurrence frequency. Early onset and hyponychial pustules may be specific to IL36RN mutation, however this alone is an insufficient biomarker for acitretin therapy. Other provocative factors play important roles in disease onset, clinical manifestations, and disease outcome. Low-dose maintenance therapy with acitretin might help reduce the recurrence of GPP.

Health state utilities and subjective well-being among psoriasis vulgaris patients in mainland China.

To investigate the validity of direct and indirect health state utility (HSU) and subjective well-being measures in psoriasis vulgaris patients. A convenience sampling framework was used to successively recruit patients with psoriasis vulgaris from the outpatient clinics of a tertiary hospital in Changsha, Central South China. Participants completed time trade-off (TTO), standard gamble (SG), the five-level EQ-5D (EQ-5D-5L), the WHO-5 well-being index, and the psoriasis disability index (PDI). The concurrent and known-groups validity of HSUs and well-being index in psoriasis patients were firstly studied. The agreements among HSUs and the relationship between HSU and well-being measures were further explored. A valid sample of 343 patients was analyzed. Mean HSU and well-being scores elicited from the EQ-5D-5L/TTO/SG and WHO-5 were 0.90/0.85/0.88 and 13.69, respectively. The Spearman correlation (concurrent validity) was the strongest between PDI and WHO-5 (r = 0.45), followed by with EQ-5D-5L (0.38), SG (r = 0.20), and the TTO (r = 0.18). The pairwise intraclass correlation coefficients among the three HSU measures were < 0.30. The known-groups validity was evident in all measures except for the SG. Exploratory factor analysis further suggests a complementary relationship between the EQ-5D-5L and WHO-5. There is a poor agreement between direct and indirect methods on measuring HSU with psoriasis vulgaris. Results from this study recommend that the EQ-5D-5L is the most preferred method to elicit HSU from psoriasis vulgaris patients in mainland China. It is important to further analyze the subjective well-being in addition to the HSU to fully understand the impact of psoriasis.

Topical Betamethasone Valerate and Calcipotriol Ointments for the Therapyof Mild and Moderate Psoriasisvulgaris: A Randomized, Comparative Study

To determine the effectiveness of both topically applied Betamethasone valerate and Calcipotriol ointments for the therapy of mild and moderate types of psoriasis. This comparative study was conducted in Jinnah Postgraduate Medical Centre, Karachi in the Pharmacology and Therapeutics department of BasicMedical Science Institute (BMSI). In 90 days study, 80 patients of mild and moderate psoriasis vulgaris were placed into A and B groups. The Betamethasone valerate treated patients were placed in group A while Calcipotriol treated patients were placed in group B; 40 patients in each group. The Psoriasis AreaSeverity Index (PASI criterion) was used to observe improvement in psoriatic patients taking these drugs. In this randomized and comparative study, psoriasis severity was checked by Psoriasis Area Severity Index (PASI). At day 90 Calcipotriol treated group B patients showed more improvement in mean PASI score ascompared to Betamethasone valerate treated group A patients. In PASI score, Calcipotriol shows 71.61% betterment whereas Betamethasone vale rate shows 63.2% betterment in mild psoriatic patients. In PASI score, Calcipotriol shows 69.21% betterment whereas Betamethasone valerate shows 60.44% betterment inmoderate psoriatic patients. In Pakistani population topically applied Calcipotriol ointment was more efficacious in the treatment of mild and moderate types of psoriasisvulgaris when compared to topically applied Betamethasone valerate ointment.

Notch1 Signaling Regulates the Th17/Treg Immune Imbalance in Patients with Psoriasis Vulgaris.

Purpose To evaluate the regulating effect of Notch1 signaling on Th17/Treg immune imbalance in psoriasis vulgaris (PV). Materials and Methods Notch1, Hes-1, RORγt, Foxp3, IL-17, and IL-10 mRNA expression, as well as Th17 and Treg cell percentages in peripheral CD4+ T cells, were detected by real-time quantitative RT-PCR and flow cytometry, and serum concentrations of IL-17 and IL-10 were detected by ELISA in 36 PV patients and 32 healthy controls. Additionally, CD4+ T cells from 12 PV patients were treated with γ-secretase inhibitor DAPT, and the above indexes were measured. Results PV patients presented distinct Th17/Treg immune imbalance and highly expressed Notch1 and Hes-1 mRNA levels, which were positively correlated with psoriasis area and severity index (PASI) and the ratios of Th17/Treg and RORγt/Foxp3. DAPT treatment resulted in the obvious downregulation of Th17 cell percentage in cocultured CD4+ T cells, RORγt and IL-17 mRNA levels, and IL-17 concentration in cell-free supernatant from cocultured CD4+ T cells of PV patients in a dose-dependent manner, while there was no significant influence on Treg cell percentage, Foxp3, and IL-10 expression, therefore leading to the recovery of Th17/Treg immune imbalance. Conclusion Notch1 signaling may contribute to the pathogenesis of PV by regulating Th17/Treg immune imbalance.

The role of single nucleotide Interleukin-6 (IL-6) polymorphism gene in Psoriasis vulgaris patients at Haji Adam Malik Central Hospital, Medan-Indonesia

Background: Psoriasis is a chronic, recidive inflammatory skin disease. The main pathogenesis process is currently unknown. This disease is known as a complex disorder, influenced by both genetic susceptibility and environmental factors.Aim: This study is aimed to analyze and determine the distribution of single nucleotide polymorphism (SNP) in IL-6 gene of psoriasis vulgaris patients and control patients.Method: This study uses a case-control design to compare SNP in the IL-6 gene between psoriasis vulgaris group and control group.Results: The most common genotype of the IL-6 gene Rs 1800795 in psoriasis vulgaris patients is GG (dominant homozygous) with a total of 21 patients (46.7%). The most common genotype allele in the control group is Gc (heterozygous) with a total of 27 patients (60%). We observed a significant correlation between the groups (p = 0.044).Conclusion:Homozygote for IL-6 allele G (GG) is a prominent finding in the case group, while in the control group heterozygous allele (Gc) is a more common finding, thus suggesting that a patient with dominant homozygote alleles will have a more severe condition when compared to those who have the heterozygote alleles.