Changes In Psoriasis Research Articles

Inflammatory nail conditions. Part 1: nail changes in psoriasis.

Nail changes are visible in a variety of inflammatory dermatoses. The commonest dermatological condition with nail manifestations is chronic plaque psoriasis. This two-part article reviews the nail signs in psoriasis in Part 1, and the nail changes in cutaneous lichen planus and alopecia areata in Part 2. It provides a brief summary of the salient points in the clinical features, management and prognosis of these entities, with practical recommendations that may be beneficial to all dermatologists.

Immunological and genetic features of pathogenetic association between psoriasis and colonic dysbiosis

Psoriasis is a multifactorial systemic immune-associated disease. It is assumed that colonic dysbiosis may contribute to its development. In this review we provide the data on colonic dysbiosis in induction and progression of psoriatic inflammation assessing a role for bacterial species: Akkermansia muciniphila, Faecalibacterium prausnitzii and Escherichia coli. On one hand, these bacterial species indicate at state of dysbiotic bacterial communities, whereas on the other hand, they are functionally associated with triggering a chain of events inducing impaired intestinal barrier transforming into chronic inflammation in the colonic mucosa and systemic inflammation. Such a scenario leads to the altered systemic reactivity of innate and adaptive immune cells, impaired function of regulatory immune cells resulting in expansion of the autoreactive skin T-cells and induction of psoriatic inflammation due to molecular mimicry between persistent Streptococcus pyogenes and cutaneous antigens. The psoriatic process is envisioned as a comorbidity with inflammatory bowel diseases. Since dysbiotic changes in psoriasis and inflammatory bowel diseases (e.g. Crohn's disease) display similar features, these diseases might potentially proceed via a similar pathogenetic chain resulting from dysbiotic changes in intestinal microbiota towards impaired intestinal barrier, chronic systemic inflammation and altered anti-inflammatory immune arm. Therefore, the data on pathogenetic pathways of the diseases comorbid with psoriasis are able to uncover yet-unknown pathogenetic components for the latter. Psoriasis as a genetically-determined disease is currently believed to be associated with single nucleotide polymorphisms (SNP) in more than four hundred genes. A role for diverse SNPs in candidate genes involved in psoriasis pathogenetic chain in antigen processing and presentation, migration of immune cells, pro-inflammatory cytokine ligation and production is discussed. Crohn's disease is associated with single nucleotide polymorphisms of the genes encoding intestinal barrier proteins potentially underlying its functional deficiency. In connection with comorbidity and similarity between microbiota-associated pathogenetic psoriasis chain and inflammatory bowel diseases, it is possible to assume that such SNPs accounting for genetic defects in the intestinal barrier are manifested as dysbiotic changes in colonic bacterial community and contribute to progression not only of inflammatory bowel diseases, but psoriasis as well.

High-throughput transcriptome and pathogenesis analysis of clinical psoriasis

BackgroundPrevious psoriasis studies have mostly focused on skin-related immunology, but the exact mechanisms remain elusive. Clinical evidence, such as higher morbidity among obese individuals and emotional factors, indicate that psoriasis is a complex systemic disease. High-throughput transcriptome analysis provides an effective method to comprehensively assess the disease. ObjectiveThe present study is aiming to understand transcriptome changes of clinical psoriasis skins and comprehensively assess the diseases using pathways analysis. MethodsWe performed transcriptome sequence of clinical psoriatic samples. Biological pathway analyses were conducted using differentially expressed RNAs, as well as identified competing endogenous RNAs (ceRNAs). qRT-PCR and histological immunofluorescence staining was conducted to verify the differentially expressed RNAs (DE_RNAs) and the three important enriched biological pathways. ResultsNumerous DE_RNAs were identified between psoriasis patients and healthy people. Functional analysis indicated PPAR-fatty acids metabolism pathways, neural-hormone regulations, circadian entrainment were the three mostly appeared pathways. For PPAR-fatty acids metabolism pathways, the expression of seven randomly selected genes, including ACSBG1, ACOT2), CYP27A1, ELOVL3, FABP7, FADS2 and PPARG were all significantly decreased in psoriasis lesions. For neural-hormone regulation pathways, the expression of CFL1, EPHA2, HRAS were all significantly upregulated in psoriasis lesions. While the expression of four randomly selected genes from circadian entrainment pathways, including CRY2, PER3, NR1D1 and RORC were all significantly downregulated. Histological immunofluorescence staining of FADS2, EPHA2 and CRY2 were consistent with their genes’ expressions. ConclusionOur results revealed transcriptome changes of psoriasis, and indicated three important pathways involved in psoriasis, including PPAR-fatty acids metabolism pathways, neural-hormone regulations, circadian entrainment.

Nail changes in various dermatoses: an observational study conducted at tertiary care center, Ujjain, Madhya Pradesh, India

<p class="abstract"><strong>Background:</strong> Nail apparatus forms an integral part to be examined for all dermatological conditions. Nail changes are seen in various dermatosis like psoriasis, onychomycosis, lichen planus, collagen vascular disease, vesicobullous diseases and other papulosquamous diseases. Aims and objective of the study was to determine the prevalence of nail changes in various dermatological conditions.</p><p class="abstract"><strong>Methods:</strong> After applying inclusion and exclusion criteria, 269 cases with various nail changes were enrolled in the study. Detailed history and thorough nail examination was carried out along with other necessary investigations like CBC, RFT, LFT, nail clipping for fungal hyphae culture and microscopy.<strong></strong></p><p class="abstract"><strong>Results:</strong> Out of 269 cases with nail disorders, male to female ratio was 1.5:1 and most common age group was 31-40 years. The most common abnormality observed was onychomycosis (34.2%) followed by nail changes in psoriasis (30.4%), LP (18.5%), eczema (4%), trachonychia (3.3%), paronychia (2.9%), lichen striatus (2.2%) and darier’s disease (0.37%). Among onychomycosis most common pattern observed was DLSO (82.6%) followed by PSO (7.6%), SWO (5.4%) and TDO (4.34%). The pattern of nail changes in psoriasis patients was pitting (30.4%), subungual hyperkeratosis (21.9%) and onycholysis (10.9%). Cases with LP had longitudinal striations (52%), thinning of nail plate and trachonychia (10% each). V shaped notching and distal splitting was seen in one of the Dariers’ disease patient.</p><p class="abstract"><strong>Conclusions:</strong> Nail changes form an indispensible part of various dermatological conditions. The pattern of involvement is unique in each and every disease. Hence examination of all the 20 nails should never be missed.</p>

Pathogenesis of psoriasis in the "omic" era. Part II. Genetic, genomic and epigenetic changes in psoriasis.

Psoriasis is a multifactorial disease in which genetic, environmental and epigenetic factors regulating gene expression play a key role. In the “genomic era”, genome-wide association studies together with target genotyping platforms performed in different ethnic populations have found more than 50 genetic susceptible markers associated with the risk of psoriasis which have been identified so far. Up till now, the strongest association with the risk of the disease has been proved for HLA-C*06 gene. The majority of other psoriasis risk SNPs are situated near the genes encoding molecules involved in adaptive and innate immunity, and skin barrier function. Many contemporary studies indicate that the epigenetic changes: histone modification, promoter methylations, long non-coding and micro-RNA hyperexpression are considered as factors contributing to psoriasis pathogenesis as they regulate abnormal keratinocyte differentiation and proliferation, aberrant keratinocytes – inflammatory cells communication, neoangiogenesis and chronic inflammation. The circulating miRNAs detected in the blood may become specific markers in the diagnosis, prognosis and response to the treatment of the disease. The inhibition of expression in selected miRNAs may be a new promising therapy option for patients with psoriasis.

BMP7 aberrantly induced in the psoriatic epidermis instructs inflammation-associated Langerhans cells

Epidermal hyperplasia represents a morphologic hallmark of psoriatic skin lesions. Langerhans cells (LCs) in the psoriatic epidermis engage with keratinocytes (KCs) in tight physical interactions; moreover, they induce T-cell-mediated immune responses critical to psoriasis. This study sought to improve the understanding of epidermal factors in psoriasis pathogenesis. BMP7-LCs versus TGF-β1-LCs were phenotypically characterized and their functional properties were analyzedusing flow cytometry, cell kinetic studies, co-culture with CD4 T cells, and cytokine measurements. Furthermore, immunohistology of healthy and psoriatic skin was performed. Additionally, invivo experiments with Junf/fJunBf/fK5cre-ERT mice were carried out to assess the role of bone morphogenetic protein (BMP) signaling in psoriatic skin inflammation. This study identified a KC-derived signal (ie, BMP signaling) to promote epidermal changes in psoriasis. Whereas BMP7 is strictly confined to the basal KC layer in the healthy skin, it is expressed at high levels throughout the lesional psoriatic epidermis. BMP7 instructs precursor cells to differentiate into LCs that phenotypically resemble psoriatic LCs. These BMP7-LCs exhibit proliferative activity and increased sensitivity to bacterial stimulation. Moreover, aberrant high BMP signaling in the lesional epidermis is mediated by a KC intrinsic mechanism, as suggested from murine data and clinical outcome after topical antipsoriatic treatment in human patients. These data indicate that available TGF-β family members within the lesional psoriatic epidermis preferentially signal through the canonical BMP signaling cascade to instruct inflammatory-type LCs and to promote psoriatic epidermal changes. Targeting BMP signaling might allow to therapeutically interfere with cutaneous psoriatic manifestations.

DNA methylation and inflammatory skin diseases.

Epigenetics is the study of heritable changes in gene expression that do not originate from alternations in the DNA sequence. Epigenetic modifications include DNA methylation, histone modification, and gene silencing via the action of microRNAs. Epigenetic dysregulation has been implicated in many disease processes. In the field of dermatology, epigenetic regulation has been extensively explored as a pathologic mechanism in cutaneous T-cell lymphoma (CTCL), which has led to the successful development of epigenetic therapies for CTCL. In recent years, the potential role of epigenetic regulation in the pathogeneses of inflammatory skin diseases has gained greater appreciation. In particular, epigenetic changes in psoriasis and atopic dermatitis have been increasingly studied, with DNA methylation the most rigorously investigated to date. In this review, we provide an overview of DNA methylation in inflammatory skin diseases with an emphasis on psoriasis and atopic dermatitis.

Study on the effect of spleen deficiency on the pathogenesis of psoriasis based on intestinal microbiome

Psoriasis is a chronic inflammatory skin disease. In recent years, studies have found that intestinal microecology has undergone significant changes in psoriasis. Due to the regulatory effect of intestinal microecology on the immune system, disordered intestinal microecology plays an important role in the occurrence and development of psoriasis. Traditional Chinese medicine believes that spleen deficiency is an important basis of intestinal microecological disorder. The process and symptoms of psoriasis with spleen deficiency are more prolonged and difficult to recover, which are easy to recurrence. Improving the spleen deficiency can adjust the quantity and variety of intestinal flora and its metabolites, so as to alleviate the symptoms and improve the prognosis of psoriasis.

Quantification of histopathological changes in patients with psoriasis before and after phototherapy.

One of the most used resources for the treatment of psoriasis is ultraviolet radiation (UV) with psoralens (PUVA) and narrow-band UV (UVB-NB 311-312nm). Although many researchers have assessed the histopathological effects of this therapy modality, none used a morphological classification system specific to psoriasis. To assess the clinical and histopathological response in the phototherapy treatment of plaque psoriasis with PUVA and UVB-NB with use of PASI and TROZAK. Histopathological changes of plaque psoriasis were quantified with help of the grading system for psoriasis-Trozak in 20 patients of both sexes, before and after 32 PUVA phototherapy sessions (10 patients-GPUVA) and UVB-NB (10 patients-GUVB-NB). The severity and extension of psoriasis was evaluated through PASI. The slides stained with hematoxylin and eosin were scanned in an Aperio CS2 scanner (Leica Biosystems) and evaluated through the software ImageScopeTM (Aperio Technologies). Statistical analysis was performed with the use of the program SPSS 22.0, with application of the Wilcoxon and Mann-Whitney tests. All patients presented improvement in psoriatic plaques with decrease in PASI after treatment (P<0.01) and significant reduction in histopathological changes in psoriasis from 15.4±1.7 to 3.7±3.2 (P<0.01) in group GPUVA and from 13.2±1.7 to 4.9±5.2 (P<0,01) in group GUVB-NB. Phototherapy, regardless of type, is an effective treatment for moderate and severe psoriasis, with possibility of being quantified clinically by PASI and histopathologically by Trozak.

Dermoscopic features of psoriasis of the skin, scalp and nails - a systematic review.

Dermoscopy is a non-invasive in-office method, which enables the diagnosis of many dermatoses and reduces the need for performing biopsies. To date, no systematic review about the diagnostic usability of dermoscopy in psoriasis has been available. The objective of this article was to summarize and critically analyse literature data on the dermoscopy of skin, scalp and nail changes in psoriasis. A systematic search of three medical databases was performed. A total of 45 articles were included into the analysis. Cutaneous psoriatic lesions assessed in all studies at a low magnification showed regularly distributed red dots. At a 50-fold or higher magnification capillary bushes (glomerular vessels) with a diameter range of 50-146μm were observed. The background colour was described as reddish or pinkish with white or yellowish scales. The most frequent dermoscopic (trichoscopic) feature of scalp psoriasis was the presence of red dots/globules and twisted red loops. Typical dermoscopic (onychoscopic) signs of nail psoriasis were onycholysis, salmon patches and splinter haemorrhages. There is an accumulating body of evidence that dermoscopy (both handheld and videodermoscopy) is a useful tool in differential diagnosis in doubtful cases of psoriasis of the skin, scalp, nails, palms, soles and genital regions.

Association Study of the Caspase Gene Family and Psoriasis Vulgaris Susceptibility in Northeastern China.

Background Abnormal apoptosis of keratinocytes is one of the pathological changes of psoriasis. Caspases (CASPs) are the central engines of apoptosis. Studies to date have shown that some SNPs alter the expression of related genes and lead to changes in disease risk. However, no studies have investigated the associations between gene polymorphisms and the risk of psoriasis in Han population in northeast China. Therefore, we conducted a case-control study to explore this question in Han population of northeastern China. Methods 540 patients with PsV and 612 healthy age- and sex-matched controls were enrolled in this study. We determined the genotypes of 17 single nucleotide polymorphisms (SNPs) from 11 genes of caspase family by the improved multiplex ligation detection reaction (iMLDR) method. A model-based single SNP frequentist test and haplotype association studies were performed to evaluate the association between SNPs and PsV. Results In the single SNP tests, rs6704688 in CASP8 was significantly associated with psoriasis vulgaris (PsV) in Han population of northeastern China (P = 0.0169, P' = 0.0179 under the additive model; P = 0.0126, P' = 0.0149 under the heterozygous model). In haplotype analyses, the CASP7 haplotype GC was found to be associated with PsV risk (case group versus control group, 47.2% versus 54.4%, respectively, p = 0.0149). Conclusions Our study presented that the gene polymorphisms of CASP7 and CASP8 were significantly associated with PsV in Han population of northeastern China, which implied the functional relationship between PsV and caspase genes. CASP8 and CASP7 SNPs could be new potential biomarkers for risk stratification and prevention of PsV.

Study of Nail Changes in Psoriasis

Psoriasis is a common, chronic and recurrent inflammatory disease of the skin. Clinically, disease can present with cutaneous and nail lesions. Both fingernails and toenails may be affected. The present study was conducted to study the abnormal nail changes in patients with psoriasis and to find correlation between nail changes and some clinical parameters. The study was undertaken in Skin &amp; VD outpatient department of Rajshahi Medical College Hospital, Rajshahi. One hundred patients of psoriasis of all age and both sexes were enrolled for studying the nail changes, in whom diagnosis of psoriasis was made clinically. In any case of abnormalities clinically suspected of fungal infection, further mycological investigations were performed. Nail changes were present in 60 patients (60%, P&lt;0.05) with psoriasis. Pitting was the most common finding on fingernails (70%), followed by onycholysis (35%). Subungual hyperkeratosis was the most common finding in toenails (34.37%). A very strong association was seen between nail changes and joint pain. There was positive correlation between nail abnormalities and duration of psoriasis. Nail involvement is common in patients with psoriasis. Pitting, onycholysis, subungual hyperkeratosis are the most frequent nail changes in psoriatic patients.TAJ 2016; 29(1): 29-32

Overexpressed fibulin-3 contributes to the pathogenesis of psoriasis by promoting angiogenesis.

Psoriasis is a chronic inflammatory skin disease. The earliest and most significant pathological change in psoriasis is angiogenesis. Fibulin-3 (Fib3) (also known as epidermal growth factor-containing fibulin-like extracellular matrix protein 1; EFEMP1) is a widely expressed extracellular matrix glycoprotein, which plays an important but contradictory role in regulating angiogenesis. However, the contribution of Fib3 to psoriasis remains unknown. To investigate the role of Fib3 in the pathogenesis of psoriasis. We first examined Fib3 expression in psoriasis cells and patient samples. We then investigated the relationship between Fib3 and angiogenesis by coculturing keratinocytes with vascular endothelial cells. Finally, we tested the therapeutic effect of a Fib3 antibody in a mouse model of psoriasis. Fib3 was overexpressed in the lesional skin of patients with psoriasis, and Fib3 levels positively correlated with psoriasis progression. Using a keratinocyte andendothelial cell coculture system, we found that keratinocyte-derived Fib3 upregulated vascular endothelial growth factor (VEGF) expression in endothelial cells and induced endothelial cell proliferation and migration. Topical application or subcutaneous injection of the Fib3 antibody decreased Psoriasis Area and Severity Index and VEGF expression in imiquimod-treated mice. Taken together, these results suggest that Fib3 is involved in the pathogenesis of psoriasis by promoting angiogenesis. Fib3 could serve as a potential target for treating psoriasis.

Reporting of outcomes in randomized controlled trials on nail psoriasis: a systematic review

One of the important complications of the skin disease, psoriasis, is the appearance of changes in the nails. These range from the formation of small pits across the surface of the nail to painful separation of the nail plate from the underlying nail bed and disfiguring enlargement and thickening of the nail itself. Given this wide range of changes in appearance it is important that, in assessing the results of treatment, researchers can use simple, but accurate, criteria for measuring changes in psoriatic nails under treatment; these are known as core outcome sets. This study, organised by investigators from the departments of dermatology in the Universities of Amsterdam and Nijmegen in the Netherlands, surveyed 65 clinical trials focussing on nail psoriasis, all of which used assessment measures for nail changes in psoriasis, the commonest of which is called the nail psoriasis severity index. However, they found that several different methods were used in the various studies. A detailed analysis of these studies has identified a number of variations in the methods used which make the results of different treatments difficult to compare. This is particularly because there was no standard way of expressing the final scores of the severity of nail disease found in these studies and also that the different aspects of severity were rated differently. Some of these assessment scoring systems have not been validated (substantiated) either. The authors call for a rethink of the use of nail assessments in psoriasis and highlight the need to develop new methods which are sufficiently robust to stand up to close scrutiny. These should allow investigators to assess the different changes seen in the diseased nails in a standardised way, so that results of different studies can be compared. They suggest that a consensus group should be established to carry out this work.

Study of nail changes in psoriasis

Background: Psoriasis is a common, chronic and recurrent inflammatory disease of the skin. Clinically, disease can present with cutaneous and nail lesions. Both fingernails and toenails may be affected.Objectives: The present study was conducted to study the abnormal nail changes in patients with psoriasis and to find correlation between nail changes and some clinical parameters.Materials &amp; Methods: The study was undertaken in Skin &amp; VD outpatient department of Rajshahi Medical College Hospital, Rajshahi. One hundred patients of psoriasis of all age and both sexes were enrolled for studying the nail changes, in whom diagnosis of psoriasis was made clinically. In any case of abnormalities clinically suspected of fungal infection, further mycological investigations were performed.Results: Nail changes were present in 60 patients (60%, P&lt;0.05) with psoriasis. Pitting was the most common finding on fingernails (70%), followed by onycholysis (35%). Subungual hyperkeratosis was the most common finding in toenails (34.37%). A very strong association was seen between nail changes and joint pain. There was positive correlation between nail abnormalities and duration of psoriasis.Conclusion: Nail involvement is common in patients with psoriasis. Pitting, onycholysis, subungual hyperkeratosis are the most frequent nail changes in psoriatic patients.KYAMC Journal Vol. 8, No.-2, Jan 2018, Page 24-26

Epidemiology and Medication Pattern Change of Psoriatic Diseases in Taiwan from 2000 to 2013: A Nationwide, Population-based Cohort Study.

To analyze the trend of prevalence and incidence rates for psoriatic arthritis (PsA) and psoriasis in Taiwan, and to determine the changes in medication patterns. Data were collected from the Taiwan National Health Insurance Research Database, which covered at least 95% of the population from 2000 to 2013. International Classification of Diseases, 9th edition (ICD-9) was used to identify PsA (ICD-9 696.0) and other psoriasis (ICD-9 696.1). Medications were identified by Anatomical Therapeutic Chemical Classification code. We calculated the annual age standardized prevalence and incidence rate of PsA and psoriasis in individuals aged ≥ 16 years from 2000 to 2013, and used the Poisson regression to test the trends by Wald chi-square statistic. The prevalence (per 100,000 population) of psoriatic diseases between 2000 and 2013 increased from 11.12 to 37.75 for PsA, and from 179.2 to 281.5 for psoriasis. The incidence (per 100,000 person-yrs) increased from 3.64 to 6.91 in PsA, while there was no significant change in psoriasis. Prevalence and incidence in PsA were more rapidly increased than in psoriasis. Sex ratio (men to women) of PsA decreased from 2.0 to 1.5 in 2000 and 2013, respectively. There was an increase in the use of disease-modifying antirheumatic drugs (DMARD), especially biologics, which is significantly different from topical therapies. The prevalence and incidence rates of psoriatic disease, especially PsA, were increasing in Taiwan. The medication pattern showed an increase in DMARD and biologics, while use of topical therapies decreased.

Study of Keratinocyte Proliferation, Apoptosis and Dermal Inflammation in Psoriatic Skin Lesions Before and After Methotrexate Therapy: Which Change Is Contributing More to Clinical Severity of the Disease?

Objective: The pathogenesis of psoriasis involves T-cell mediated immunologic response, keratinocytes hyperproliferation, and resistance to apoptosis. Methotrexate is one of the most reliable modalities in the treatment of psoriasis that target those changes. The study of those variables before and after methotrexate therapy may answer the question: Which of those variables contributes more to the clinical severity of the disease and is more valuable to be targeted in psoriasis treatment. Patients and Methods: A total of 50 cases of psoriasis vulgaris were included, 25 patients received methotrexate therapy. Skin biopsies of psoriatic skin lesions before and after treatment were examined histologically for measurement of epidermal thickness and grading of dermal inflammation. Immunostaining for Ki-67 and p53 was done for assessment of keratinocyte proliferation and apoptosis. Results were correlated with clinical severity of the disease, assessed by psoriatic area and severity index (PASI) score. 15 biopsies of normal skin were included as control. Results: Dermal inflammation, Ki-67%, and p53% were significantly higher in psoriatic skin lesion than in normal skin. Those changes were significantly correlated with PASI score. Multiple logistic regression models revealed that Ki-67 was the most significant variable contributing to clinical severity. One unit change in ki-67% can explain 1.2 unit changes in PASI score with 97% sensitivity, 40% specificity and 25% cut-off value. PASI score, dermal inflammation, Ki-67% and P53% were significantly reduced after methotrexate therapy. No significant difference was detected between the percent reduction in PASI score (81%) and that of Ki-67% (70%). Conclusion: Keratinocyte proliferation was the most significant variable contributing to the clinical severity of psoriasis and it was the single parameter that showed parallel changes to PASI score after methotrexate therapy. Keratinocyte proliferation may be considered as the stimulus that induces all other pathological and clinical changes in psoriasis and should be targeted by therapy.

Study of Keratinocyte Proliferation, Apoptosis and Dermal Inflammation in Psoriatic Skin Lesions Before and After Methotrexate Therapy: Which Change Is Contributing More to Clinical Severity of the Disease?

Objective: The pathogenesis of psoriasis involves T-cell mediated immunologic response, keratinocytes hyperproliferation, and resistance to apoptosis. Methotrexate is one of the most reliable modalities in the treatment of psoriasis that target those changes. The study of those variables before and after methotrexate therapy may answer the question: Which of those variables contributes more to the clinical severity of the disease and is more valuable to be targeted in psoriasis treatment. Patients and Methods: A total of 50 cases of psoriasis vulgaris were included, 25 patients received methotrexate therapy. Skin biopsies of psoriatic skin lesions before and after treatment were examined histologically for measurement of epidermal thickness and grading of dermal inflammation. Immunostaining for Ki-67 and p53 was done for assessment of keratinocyte proliferation and apoptosis. Results were correlated with clinical severity of the disease, assessed by psoriatic area and severity index (PASI) score. 15 biopsies of normal skin were included as control. Results: Dermal inflammation, Ki-67%, and p53% were significantly higher in psoriatic skin lesion than in normal skin. Those changes were significantly correlated with PASI score. Multiple logistic regression models revealed that Ki-67 was the most significant variable contributing to clinical severity. One unit change in ki-67% can explain 1.2 unit changes in PASI score with 97% sensitivity, 40% specificity and 25% cut-off value. PASI score, dermal inflammation, Ki-67% and P53% were significantly reduced after methotrexate therapy. No significant difference was detected between the percent reduction in PASI score (81%) and that of Ki-67% (70%). Conclusion: Keratinocyte proliferation was the most significant variable contributing to the clinical severity of psoriasis and it was the single parameter that showed parallel changes to PASI score after methotrexate therapy. Keratinocyte proliferation may be considered as the stimulus that induces all other pathological and clinical changes in psoriasis and should be targeted by therapy.

The metabolomics of psoriatic disease.

Metabolomics is an emerging new “omics” field involving the systematic analysis of the metabolites in a biologic system. These metabolites provide a molecular snapshot of cellular activity and are thus important for understanding the functional changes in metabolic pathways that drive disease. Recently, metabolomics has been used to study the local and systemic metabolic changes in psoriasis and its cardiometabolic comorbidities. Such studies have revealed novel insights into disease pathogenesis and suggest new biochemical signatures that may be used as a marker of psoriatic disease. This review will discuss common strategies in metabolomics analysis, current findings in the metabolomics of psoriasis, and emerging trends in psoriatic metabolomics.

Genetic variations within the promotor region of the human histamine H4 receptor gene in psoriasis patients

Environmental triggers and genetic factors are supposed to lead to complex gene expression changes in psoriasis and interact in the manifestation of the disease. The histamine H4 receptor (HRH4) is functionally expressed on Th17 cells and plasmacytoid dendritic cells (pDCs) which play a prominent role in the pathogenesis of psoriasis. On pDCs a higher basal expression level of the HRH4 in psoriasis patients compared to healthy controls has been detected. The functional relationship between predisposing genetic variations in the HRH4 gene and psoriasis is yet not known. The aim of the study was to evaluate a possible association between single nucleotide polymorphisms (SNPs) in the HRH4 gene primarily in the promotor region and incidence, severity as well as special clinical features (nail involvement, arthritis, palmoplantar location) of psoriasis.For this approach genomic DNA from 206 patients with psoriasis and 213 healthy controls of Caucasian origin was extracted and three SNPs in the promotor region and one SNP located in an intron of the HRH4 gene were analysed by PCR and pyrophosphate DNA-sequencing.The genotype distributions and allele frequencies between the different groups were compared by chi-square test. The analysis of association between HRH4 polymorphisms and psoriasis was assessed by odds ratio with 95% confidence interval.The genotype distributions and allele frequencies of the four SNPs in the HRH4 gene did not show obvious differences between the whole group of psoriasis patients and healthy controls. However, there were differences by trend in subgroup analysis: The mutant genotypes (A/G) of rs17203314 and (G/A) of rs615283 were more frequent in patients with severe psoriasis PASI≥30 (34.8% and 34.8%) when compared to the control groups (23.5% and 27.2%), respectively. The mutant G/A genotype of rs615283 was significantly more frequent in patients with moderate-to-severe psoriasis PASI≥10 when compared to mild psoriasis PASI<10 (33.3% vs 21.7%, p=0.022). For rs524149 and rs17797945 the wildtype CC genotype was more frequent by trend in moderately-to-severely affected patients with PASI≥10 (85.2% and 63.0%) when compared to the group with mild psoriasis PASI<10 (77.0% and 49.4%), respectively. Furthermore, a significant association of rs615283 with psoriasis palmoplantaris was detected.In conclusion our study suggests that genetic variations within the HRH4 gene might be associated with special clinical features of psoriasis. Further studies are needed in larger study populations to confirm the reported associations and investigate the functional relevance of the identified SNPs.