Application of Genetic Algorithm-Based Support Vector Machine in Identification of Gene Expression Signatures for Psoriasis Classification: A Hybrid Model.

BACKGROUND: Psoriasis is a chronic autoimmune disease impairing significantly the quality of life of the patient. The diagnosis of the disease is done via a visual inspection of the lesional skin by dermatologists. Classification of psoriasis using gene expression is an important issue for the early and effective treatment of the disease. Therefore, gene expression data and selection of suitable gene signatures are effective sources of information. METHODS: We aimed to develop a hybrid classifier for the diagnosis of psoriasis based on two machine learning models of the genetic algorithm and support vector machine (SVM). The method also conducts gene signature selection. A publically available gene expression dataset was used to test the model. RESULTS: A number of 181 probe sets were selected among the original 54,675 probes using the hybrid model with a prediction accuracy of 100% over the test set. A number of 10 hub genes were identified using the protein-protein interaction network. Nine out of 10 identified genes were found in significant modules. CONCLUSIONS: The results showed that the genetic algorithm improved the SVM classifier performance significantly implying the ability of the proposed model in terms of detecting relevant gene expression signatures as the best features.

Evaluation of expression of Toll-Like Receptors 7 and 9, proliferation, and cytoskeletal biomarkers in plaque and guttate psoriasis: A pilot morphological study.

This pilot study was aimed at comparing TLR7/TLR9 expression, cytoskeletal arrangement, and cell proliferation by indirect immunofluorescence in parallel lesional and non lesional skin samples of guttate psoriasis (PG) and psoriasis vulgaris (PV) in five male patients for each group (n=10). TLR7 expression was detected throughout all the epidermal compartment in PV samples, while in PG skin was restricted to the granular layer. TLR9 was present in the granular layer of non lesional skin and in the suprabasal layers of PV/PG lesional skin. Cell proliferation was localized in all the epidermal layers in lesional PG and PV, consistently with the immunopositivity for the "psoriatic keratin" K16. In the suprabasal layers of lesional PG and PV skin, a similar K17 expression was detected and K10 exhibited a patchy distribution. The present results suggest that TLR7 expression can be considered an intrinsic and differential histomorphological feature of PV.

Renal dysfunction in psoriatic patients.

Psoriasis is a common chronic inflammatory disease of the skin that is increasingly being considered as a systemic inflammatory disorder due to its association with cardiovascular, metabolic, pulmonary, renal, liver, and neurologic diseases. Renal involvement is rare but well documented and psoriasis is recognized as an independent factor for CKD and ESKD. A careful monitoring of the urinalysis and of renal function is recommended in psoriatic patients, especially those with moderate-to-severe disease. In case of pathologic findings, the execution of a renal biopsy appears necessary to make an accurate diagnosis and to establish the most appropriate therapeutic strategies to prevent the progression of kidney damage. The mechanisms of kidney involvement are different and not yet fully clarified. We present here two case reports of renal dysfunction during psoriasis. In one case, we diagnosed IgA nephropathy with particularly severe clinical presentation; in the other, an advanced kidney injury due to nephrotoxicity after prolonged CNI treatment.

Recategorization of psoriasis severity: Delphi consensus from the International Psoriasis Council.

BACKGROUND: Psoriasis severity categories have been important tools for clinicians to use in treatment decisions as well as to determine eligibility criteria for clinical studies. However, owing to the heterogeneity of severity classifications and their lack of consideration for the impact of psoriasis involvement of special areas or past treatment history, patients may be miscategorized, which can lead to undertreatment of psoriasis. OBJECTIVE: To develop a consensus statement on the classification of psoriasis severity. METHODS: A modified Delphi approach was developed by the International Psoriasis Council to define psoriasis severity. RESULTS: After completion of the exercise, 7 severity definitions were preferentially ranked. This most preferred statement rejects the mild, moderate, and severe categories in favor of a dichotomous definition: Psoriasis patients should be classified as either candidates for topical therapy or candidates for systemic therapy; the latter are patients who meet at least one of the following criteria: (1) body surface area >10%, (2) disease involving special areas, and (3) failure of topical therapy. LIMITATIONS: This effort might have suffered from a lack of representation by all relevant stakeholders, including patients. CONCLUSION: The consensus statement describes 2 categories of psoriasis severity, while accounting for special circumstances where patients may require systemic therapy.

Ixekizumab y psoriasis, ¿qué sucede en el mundo real? / Ixekizumab and Psoriasis in the Real World

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[Severity scores for childhood psoriasis: A systematic literature review]. / Scores de sévérité dans le psoriasis de l'enfant : revue systématique de la littérature.

BACKGROUND: Psoriasis affects 0.5 to 1 % of children in Europe. It has a significant impact on quality of life. Recently, systemic treatments have been licensed for children with moderate-to-severe psoriasis. While scores to assess the severity of the disease are thus important for the management of these children, there is no standardization or consensus concerning their use in childhood psoriasis. The aim of this study was to examine the use of clinical severity scores and quality of life in children with psoriasis. PATIENTS AND METHODS: A systematic literature review was conducted on PubMed and Embase. Further research was carried out using the bibliographic references in selected articles. The following keywords were used: "psoriasis" with "pediatric", "childhood", "infant", "child" or "adolescent", and "Severity of Illness Index", "sickness impact profile", "quality of life", "index", "measure" or "score". A first selection was made from the titles and abstracts of the selected articles. RESULTS: After evaluating 1712 articles on Medline and 233 on Embase, 78 were finally selected. The Psoriasis Area Severity Index (PASI: 74.4 %) was the most frequently found score followed by the Body Surface Area (BSA: 48.7 %) and the Physician's Global Assessment (PGA: 29.5 %). Recourse to systemic therapies and failure of topical treatments were also used as severity criteria. Over half the studies did not define a severity threshold. We also observed extensive heterogeneity in the definition of psoriasis severity. The same scores were often used regardless of psoriasis type or patient age. Regarding quality of life, most studies used the Children's Dermatology Life Quality Index (CDLQI: 23.1 %) and DLQI (5.1 %). Non-specific quality-of-life scores for psoriasis were also used, such as the Pediatric Quality of Life Inventory (Peds-QL: 6.4 %) and Skindex (2.6 %). Here again, no severity threshold was defined for these scores. DISCUSSION: Severity scores are chiefly used by analogy with adults but without validation in the pediatric population. They do not consider pediatric specificities such as progression of BSA according to age, clinical aspect, clinical types, etc. Severity thresholds are rarely defined in children, whether in terms of clinical score or quality of life. This can constitute a limitation in terms of both prescription of systemic treatments and comparison between different studies. Our study demonstrates the need to validate severity and quality-of-life scores and to define child-specific thresholds.

The Impact of Ramadan Fasting on the Reduction of PASI Score, in Moderate-To-Severe Psoriatic Patients: A Real-Life Multicenter Study.

Fasting during the month of Ramadan consists of alternate abstinence and re-feeding periods (circadian or intermittent fasting). Nothing is currently known on the impact of this kind of fasting on psoriasis. A sample of 108 moderate-to-severe plaque psoriasis patients (aged 42.84 ± 13.61 years, 62 males, 46 females) volunteered to take part in the study. A significant decrease in the "Psoriasis Area and Severity Index" (PASI) score after the Ramadan fasting (mean difference = -0.89 ± 1.21, p < 0.0001) was found. At the multivariate regression, the use of cyclosporine (p = 0.0003), interleukin-17 or IL-17 blockers (p < 0.0001), and tumor necrosis factor or TNF blockers (p = 0.0107) was independently associated with a low PASI score, while the use of apremilast (p = 0.0009), and phototherapy (p = 0.0015) was associated with a high PASI score before the Ramadan fasting. Similarly, the consumption of cyclosporine (p < 0.0001), IL-17 blockers (p < 0.0001), mammalian target of rapamycin or mTOR inhibitors (p = 0.0081), and TNF blockers (p = 0.0017) predicted a low PASI score after the Ramadan fasting. By contrast, narrow band ultraviolet light B or NB-UVB (p = 0.0015) was associated with a high PASI score after Ramadan fasting. Disease duration (p = 0.0078), use of apremilast (p = 0.0005), and of mTOR inhibitors (p = 0.0034) were independent predictors of the reduction in the PASI score after the Ramadan fasting. These findings reflect the influence of dieting strategy, the biological clock, and circadian rhythm on the treatment of plaque psoriasis.

Translation and validation of the Simplified Psoriasis Index (SPI) into Brazilian Portuguese

Abstract: Background: The Simplified Psoriasis Index is a tool that assesses the current severity, psychosocial impact, past history and interventions in patients with psoriasis through separate components. Two versions are available, one in which the current severity of the disease is evaluated by the patient themselves and another by the physician. Objectives: Translate the Simplified Psoriasis Index into Brazilian Portuguese and verify its validity. Methods: The study was conducted in two stages; the first stage was the translation of the instrument; the second stage was the instrument's validation. Results: We evaluated 62 patients from Complexo Hospitalar Santa Casa de Porto Alegre and Hospital Universitário de Brasília. The Simplified Psoriasis Index translated into Portuguese showed high internal consistency (Cronbach test 0.68). Study limitations: Some individuals, because of poor education, might not understand some questions of the Simplified Psoriasis Index. Conclusions: The Brazilian Portuguese version of the Simplified Psoriasis Index was validated for our population and can be recommended as a reliable instrument to assess the patients with psoriasis.

Translation and validation of the Simplified Psoriasis Index (SPI) into Brazilian Portuguese.

BACKGROUND: The Simplified Psoriasis Index is a tool that assesses the current severity, psychosocial impact, past history and interventions in patients with psoriasis through separate components. Two versions are available, one in which the current severity of the disease is evaluated by the patient themselves and another by the physician. OBJECTIVES: Translate the Simplified Psoriasis Index into Brazilian Portuguese and verify its validity. METHODS: The study was conducted in two stages; the first stage was the translation of the instrument; the second stage was the instrument's validation. RESULTS: We evaluated 62 patients from Complexo Hospitalar Santa Casa de Porto Alegre and Hospital Universitário de Brasília. The Simplified Psoriasis Index translated into Portuguese showed high internal consistency (Cronbach test 0.68). STUDY LIMITATIONS: Some individuals, because of poor education, might not understand some questions of the Simplified Psoriasis Index. CONCLUSIONS: The Brazilian Portuguese version of the Simplified Psoriasis Index was validated for our population and can be recommended as a reliable instrument to assess the patients with psoriasis.

A cross-sectional study of the distribution of psoriasis subtypes in different ethno-racial groups.

Skin of colored patients with psoriasis are more likely to remain undiagnosed and experience a greater impact on quality of life than their white counterparts. A better understanding of the ethno-racial differences in the presentation of psoriasis can help address these disparities. To compare the prevalence of psoriatic subtypes (plaque, guttate, pustular, erythrodermic, palmoplantar, and inverse) and lesion locations in Caucasian, Asian, and Hispanic/Latino patients, we analyzed cross-sectional, patient-reported, physician-reviewed survey data from 882 adult and 16 pediatric psoriasis patients seen at the University of California, San Francisco Department of Dermatology between 2006 and 2016. Multivariate logistic regression was used to compare the prevalence of psoriasis subtypes and lesional distributions amongst the ethno-racial groups. Asians and Hispanics/Latinos had higher odds of having pustular psoriasis compared to Caucasians (OR=4.36 [95%CI: 1.24-17.62], P=0.026; and OR=5.94 [95%CI: 1.03-31.03], P=0.036, respectively). Asians also had a higher frequency of erythrodermic psoriasis (OR=5.56 [95%CI: 1.41-27.17], P=0.018), but a lower frequency of inverse psoriasis compared to Caucasians (OR=0.26 [95%CI: 0.06-0.80], P=0.036). These differences may relate to genetic or environmental factors or access to care. Clinician awareness of ethno-racial differences in psoriasis subtype and lesion location can facilitate earlier diagnosis and therapeutic intervention.

The distinct role and regulatory mechanism of IL-17 and IFN-γ in the initiation and development of plaque vs guttate psoriasis.

BACKGROUND: Few studies have explored the differences of immunopathogenesis in plaque vs guttate psoriasis, especially on the inhibitory role of regulatory T cells (Tregs) on IL-17/ IFN-γ production and the impact of CD4+T cells on keratinocytes. OBJECTIVE: To investigate the percentage and inhibitory function of CD4+CD25highTreg and differential expressions of IL-17/ IFN-γ in plaque vs guttate psoriasis, and the effects of CD4+T cells on the proliferation of keratinocytes. METHODS: Peripheral blood mononuclear cells (PBMCs) were prepared from patients with the plaque and guttate psoriasis. The percentage of CD4+CD25high Tregs, IL-17/IFN-γ- producing CD4+ or CD8+T cells, and apoptosis and cell cycle of Hacat cells were determined by flow cytometry. The level of IFN-γ in supernatants was analyzed by ELISA. RESULTS: The percentage of CD4+CD25highTregs in plaque psoriasis was significantly increased, and they can inhibit IFN-γ production from CD4+CD25- effector T cells. The percentage of CD8+IFN-γ+cells was also significantly increased in plaque psoriasis, and these cells positively correlated with disease severity. The percentage of CD4+CD25highTregs was decreased and CD4+IFN-γ+/IFN-γ+IL-17+ cells were predominantly increased in guttate psoriasis. CD4+T cells from guttate psoriasis induce apoptosis of keratinocytes while they promote the proliferation of keratinocytes in plaque psoriasis by decreasing late apoptosis and increasing the percentage of G1 phase. CONCLUSION: There was considerable discrepancy of the phenotype and function of T cells between plaque vs guttate psoriasis. IFN-γ and IL-17 from CD4+T cells play a crucial role in guttate psoriasis, however, IFN-γ and IL-17 from CD8+T cells are more important in the immunopathogenesis of plaque psoriasis.

Generalized pustular psoriasis - a model disease for specific targeted immunotherapy, systematic review.

Generalized pustular psoriasis (GPP) is a rare, multisystemic skin disease characterized by recurrent episodes of pustulation. GPP can be life-threatening and is often difficult to treat. In the era of precision medicine in dermatology, GPP stands exemplary for both challenges and chances-while new treatments offer great hope, there is urgent need for better definition and stratification of this severe and heterogeneous disease. Our objective was to systematically review the literature for evidence of efficacy of targeted immunotherapy and their mode of action in the context of clinical phenotype, classification and pathogenesis of adult GPP. Classifying GPP is challenging since clinical criteria for description and diagnosis are not consistent between expert centres. We therefore defined diagnostic feasibility of the reviewed cases by assessing four criteria: compatible clinical history, typical dermatological features and/or diagnostic histopathology, consistent clinical pictures and the DITRA status. Pathogenesis of GPP is mediated by pathways that partly overlap plaque type psoriasis, with a more pronounced activity of the innate immune system. Both IL-1 and IL-36 but also IL-17 play a major role in disease formation. We ascertained a total of 101 published cases according to our predefined criteria and identified TNF-α, IL-12/23, IL-17 and IL-1ß as targets for immunotherapy for the treatment of GPP. Of those cases, 61% showed complete response and 27% partial response to targeted immunotherapy. Only 12% experienced weak or no response. These data indicate that specific immunotherapy can be used to effectively treat GPP, with most evidence existing for anti-IL-17 agents.

DNA methylation-based subclassification of psoriasis in the Chinese Han population.

Psoriasis (Ps) is an inflammatory skin disease caused by genetic and environmental factors. Previous studies on DNA methylation (DNAm) found genetic markers that are closely associated with Ps, and evidence has shown that DNAm mediates genetic risk in Ps. In this study, Consensus Clustering was used to analyze DNAm data, and 114 Ps patients were divided into three subclassifications. Investigation of the clinical characteristics and copy number variations (CNVs) of DEFB4, IL22, and LCE3C in the three subclassifications revealed no significant differences in gender ratio and in Ps area and severity index (PASI) score. The proportion of late-onset ( ≥ 40 years) Ps patients was significantly higher in type I than in types II and III (P = 0.035). Type III contained the smallest proportion of smokers and the largest proportion of non-smoking Ps patients (P = 0.086). The CNVs of DEFB4 and LCE3C showed no significant differences but the CNV of IL22 significantly differed among the three subclassifications (P = 0.044). This study is the first to profile Ps subclassifications based on DNAm data in the Chinese Han population. These results are useful in the treatment and management of Ps from the molecular and genetic perspectives.