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15 pages, 7357 KiB

Open AccessArticle

Transcriptional Analysis-Based Alterations Affecting Neuritogenesis of the Peripheral Nervous System in Psoriasis

by Dóra Romhányi, Kornélia Szabó, Lajos Kemény, Endre Sebestyén and Gergely Groma

Life 2022, 12(1), 111; https://doi.org/10.3390/life12010111 - 13 Jan 2022

Cited by 6 | Viewed by 3190

Abstract

An increasing amount of evidence indicates the critical role of the cutaneous nervous system in the initiation and maintenance of psoriatic skin lesions by neurogenic inflammation. However, molecular mechanisms affecting cutaneous neurons are largely uncharacterized. Therefore, we reanalyzed a psoriatic RNA sequencing dataset [...] Read more.

An increasing amount of evidence indicates the critical role of the cutaneous nervous system in the initiation and maintenance of psoriatic skin lesions by neurogenic inflammation. However, molecular mechanisms affecting cutaneous neurons are largely uncharacterized. Therefore, we reanalyzed a psoriatic RNA sequencing dataset from published transcriptome experiments of nearly 300 individuals. Using the Ingenuity Pathway Analysis software, we associated several hundreds of differentially expressed transcripts (DETs) to nervous system development and functions. Since neuronal projections were previously reported to be affected in psoriasis, we performed an in-depth analysis of neurite formation-related process. Our in silico analysis suggests that SEMA-PLXN and ROBO-DCC-UNC5 regulating axonal growth and repulsion are differentially affected in non-lesional and lesional skin samples. We identified opposing expressional alterations in secreted ligands for axonal guidance signaling (RTN4/NOGOA, NTNs, SEMAs, SLITs) and non-conventional axon guidance regulating ligands, including WNT5A and their receptors, modulating axon formation. These differences in neuritogenesis may explain the abnormal cutaneous nerve filament formation described in psoriatic skin. The processes also influence T-cell activation and infiltration, thus highlighting an additional angle of the crosstalk between the cutaneous nervous system and the immune responses in psoriasis pathogenesis, in addition to the known neurogenic pro-inflammatory mediators. Full article

(This article belongs to the Special Issue Psoriasis: New Developments and Concepts in Pathogenesis and Treatment)

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11 pages, 817 KiB

Open AccessArticle

Use of Biological Treatments in Elderly Patients with Skin Psoriasis in the Real World

by Cristina Galache Osuna, Sebastián Reyes García, Jimena Carrero Martín, Virginia García Jiménez, Francisco Vázquez López and Jorge Santos-Juanes

Life 2021, 11(12), 1348; https://doi.org/10.3390/life11121348 - 7 Dec 2021

Cited by 7 | Viewed by 3156

Abstract

Biological drugs have prompted a revolution in the treatment of patients with psoriasis because of their favourable efficacy/risk profile. The aims of our study are to determine whether there is any difference in the pattern of use of biological treatments for older (65+ [...] Read more.

Biological drugs have prompted a revolution in the treatment of patients with psoriasis because of their favourable efficacy/risk profile. The aims of our study are to determine whether there is any difference in the pattern of use of biological treatments for older (65+ years) and younger patients diagnosed with plaque psoriasis by the Dermatology Service of the Hospital Universitario de Asturias (HUCA), to understand the survival of these drugs, and to identify the factors that predict the discontinuation of treatments. We report a retrospective observational hospital-based study of 300 patients registered at HUCA’s Dermatology Service who were receiving one of the following biological treatments for psoriasis on 30 November 2020: adalimumab, ustekinumab, secukinumab, or ixekizumab. The age groups were compared using Student’s t-test for quantitative variables and the chi-squared test for qualitative variables. We used the Kaplan–Meier estimator to estimate the survival function and the log-rank test to measure differences. No statistically significant differences in the frequency of use were noted between the younger and older groups, for any of the drugs studied. Survival on a drug regime, globally and individually, was similar in the two age groups. Factors predicting lower overall survival were being female, obesity, and having undergone previous biological treatment. The first three factors were influential in the under-65-year-old group, while arthritis was a significant factor for the older group. Full article

(This article belongs to the Special Issue Psoriasis: New Developments and Concepts in Pathogenesis and Treatment)

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10 pages, 987 KiB

Open AccessArticle

Which PASI Outcome Is Most Relevant to the Patients in Real-World Care?

by Natalia Kirsten, Stephan Rustenbach, Ralph von Kiedrowski, Christina Sorbe, Kristian Reich and Matthias Augustin

Life 2021, 11(11), 1151; https://doi.org/10.3390/life11111151 - 28 Oct 2021

Cited by 11 | Viewed by 2557

Abstract

In psoriasis treatment, there is a high need to define meaningful endpoints and differences from the patient perspective to analyze patient-relevant differences of frequently used outcome methods for psoriasis under real-world conditions. A sample of 3116 patients from the German Psoriasis-Registry PsoBest was [...] Read more.

In psoriasis treatment, there is a high need to define meaningful endpoints and differences from the patient perspective to analyze patient-relevant differences of frequently used outcome methods for psoriasis under real-world conditions. A sample of 3116 patients from the German Psoriasis-Registry PsoBest was analyzed for clinical as well as patient-reported outcomes (PRO) after 3- and 6-month treatment. The parameters PASI, DLQI, and PBI were intercorrelated and related to two anchoring variables: (1) patient satisfaction with treatment and (2) perceived complete clearance. Baseline data were as follows: PASI 10.5 ± 9.1, DLQI 12.4 ± 3.4, and PBI 2.7 ± 0.3. There was an almost linear relationship between “complete patient satisfaction” and the relative differences in PASI in the range from PASI 25 to PASI 90. However, there was no additional benefit between PASI 90 and PASI 100. The same finding resulted from the anchoring variable “perception of complete healing”. When related to DLQI outcomes, relative PASI changes as well as absolute changes and PASI at 3 and 6 months showed relevant differences between the PASI classes 25 to 90 but not between PASI 90 and PASI 100. Under real-world conditions, changes in PASI and DLQI reflect patient-relevant benefits. Full article

(This article belongs to the Special Issue Psoriasis: New Developments and Concepts in Pathogenesis and Treatment)

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14 pages, 760 KiB

Open AccessArticle

Leptin Receptor (rs1137101) and Brain-Derived Neurotrophic Factor (rs925946) Gene Variants Are Associated with Obesity in the Early- but Not in the Late-Onset Population of Hungarian Psoriatic Patients

by Zita Szentkereszty-Kovács, Szilvia Fiatal, Eszter Anna Janka, Dóra Kovács, Andrea Szegedi, Éva Remenyik and Dániel Törőcsik

Life 2021, 11(10), 1086; https://doi.org/10.3390/life11101086 - 14 Oct 2021

Cited by 6 | Viewed by 2365

Abstract

Background: Psoriatic patients have considerably higher odds of being obese compared with the general population; however, the exact pathophysiological link between psoriasis and obesity needs to be elucidated. Methods: To investigate the association of psoriasis with established obesity-related gene variants, we conducted a [...] Read more.

Background: Psoriatic patients have considerably higher odds of being obese compared with the general population; however, the exact pathophysiological link between psoriasis and obesity needs to be elucidated. Methods: To investigate the association of psoriasis with established obesity-related gene variants, we conducted a population-based case-control study including 3541 subjects (574 psoriasis cases and 2967 controls from the general Hungarian population). Genotyping of 20 SNPs at ADIPOQ, BDNF, FTO, GNPDA2, LEPR, MC4R, NEGR1, NPY, PPARG, TMEM18, and UCP2 were determined, and differences in genotype and allele distributions were investigated. Multiple logistic regression analyses were implemented. Results: Analysis revealed an association between the G allele of the rs1137101 polymorphism (LEPR gene) and obesity risk (OR: 3.30 (1.45; 7.50), p = 0.004) in the early-onset group of psoriatic patients. Furthermore, the T allele of rs925946 polymorphism (BDNF gene) was also associated with increased risk of obesity in early-onset psoriasis (OR: 2.26 (1.24; 4.14), p = 0.008). Conclusions: Our results suggest that in psoriatic patients, there are prominent differences in the causes of obesity that should be accounted for, including not only environmental factors but also patient characteristics, such as the time of disease onset as well as genetic factors. Full article

(This article belongs to the Special Issue Psoriasis: New Developments and Concepts in Pathogenesis and Treatment)

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14 pages, 4892 KiB

Open AccessArticle

Impact of Interleukin-17 Inhibitor Therapy on Arterial Intima-media Thickness among Severe Psoriatic Patients

by Éva Anna Piros, Ákos Szabó, Fanni Rencz, Valentin Brodszky, Klára Szalai, Noémi Galajda, Bálint Szilveszter, Edit Dósa, Béla Merkely and Péter Holló

Life 2021, 11(9), 919; https://doi.org/10.3390/life11090919 - 5 Sep 2021

Cited by 12 | Viewed by 2428

Abstract

Background: Psoriasis is frequently accompanied by cardiovascular diseases based on the shared immunopathogenic pathway. Authors determined the effect of interleukin (IL)-17 inhibitor therapy on arterial intima-media thickness (IMT) among severe psoriatic patients. Methods: Thirty-one severe psoriatic patients were enrolled. Twenty received secukinumab and [...] Read more.

Background: Psoriasis is frequently accompanied by cardiovascular diseases based on the shared immunopathogenic pathway. Authors determined the effect of interleukin (IL)-17 inhibitor therapy on arterial intima-media thickness (IMT) among severe psoriatic patients. Methods: Thirty-one severe psoriatic patients were enrolled. Twenty received secukinumab and 11 received ixekizumab. Before treatment initiation and after 6 months, the carotid-brachial-femoral IMT, the Psoriasis Area Severity Index (PASI), the Dermatology Life Quality of Index (DLQI) and the EuroQol Visual Analogue Scale (EQ VAS) were evaluated. Results: After 6 months, significant ameliorations were observed in PASI (p < 0.001) from 18 to 0, in DLQI (p < 0.001) from 17 to 0, in EQ VAS (p < 0.001) from 60 to 90, in right carotid IMT (p < 0.001) from 1.1 mm to 0.8 mm, in left carotid IMT (p < 0.001) from 1.1 mm to 0.7 mm, in right brachial IMT (p < 0.001) from 0.75 mm to 0.6 mm, in left brachial IMT (p < 0.001) from 0.8 mm to 0.5 mm, in right femoral IMT (p < 0.001) from 0.9 mm to 0.7 mm and in left femoral IMT (p < 0.001) from 0.8 mm to 0.7 mm. Conclusions: By reducing the inflammation of the vascular wall, anti-IL-17 therapy may have a beneficial long-term effect on cardiovascular complications of systemic inflammation. Full article

(This article belongs to the Special Issue Psoriasis: New Developments and Concepts in Pathogenesis and Treatment)

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10 pages, 1023 KiB

Open AccessArticle

The Genetic Variants of NOTCH3 (6746T>C) and PSMA6 (-8C>G) as Possible Risk Factors of Psoriasis Development

by Joanna Bartosińska, Szymon Zmorzyński, Beata Sarecka-Hujar, Dorota Raczkiewicz, Magdalena Wojcierowska-Litwin, Iwona Korszeń-Pilecka, Anna Michalak-Stoma, Małgorzata Kowal, Jarosław Bartosiński, Agata Filip, Dorota Krasowska and Grażyna Chodorowska

Life 2021, 11(9), 887; https://doi.org/10.3390/life11090887 - 28 Aug 2021

Viewed by 2055

Abstract

Advances in genotypic technologies enable identification of possible associations between genetic variants of certain genes and increased risk of developing plaque psoriasis or psoriatic arthritis. The aim of the study was to analyze the NOTCH3 (6746T>C) (rs1044009) and PSMA6 (-8C>G) (rs1048990) polymorphisms and [...] Read more.

Advances in genotypic technologies enable identification of possible associations between genetic variants of certain genes and increased risk of developing plaque psoriasis or psoriatic arthritis. The aim of the study was to analyze the NOTCH3 (6746T>C) (rs1044009) and PSMA6 (-8C>G) (rs1048990) polymorphisms and their role in genetic susceptibility to psoriasis. The study included 158 psoriatic patients and 100 healthy controls. The frequencies of the NOTCH3 genotypes differed between the psoriatic patients and healthy controls (p = 0.050). No differences were found in the distribution of PSMA6 genotypes and alleles between the psoriatic patients and healthy controls. The studied psoriatic patients presented a higher frequency of the CC genotype of PSMA6 compared to the healthy controls (8.8% vs. 2%, respectively). Psoriatic arthritis was more frequent among patients with the CC genotype of PSMA6 (p = 0.059). CC homozygosity of NOTCH3 was more commonly observed in the studied psoriatic patients than in the healthy controls (OR = 4.76, p= 0.032). The obtained data suggest that genetic variants of NOTCH3 (6746T>C) and PSMA6 (-8C>G) genes may play significant roles in psoriatic patients. Further studies are necessary to unequivocally determine their role as genetic risk factors of psoriasis development. Full article

(This article belongs to the Special Issue Psoriasis: New Developments and Concepts in Pathogenesis and Treatment)

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15 pages, 6595 KiB

Open AccessArticle

Establishment of an Intradermal Ear Injection Model of IL-17A and IL-36γ as a Tool to Investigate the Psoriatic Cytokine Network

by David Kluwig, Sebastian Huth, Ali T. Abdallah, Carolina M. Pfaff, Katharina Fietkau, Laura Huth, Yvonne Marquardt, Jens M. Baron and Bernhard Lüscher

Life 2021, 11(8), 846; https://doi.org/10.3390/life11080846 - 19 Aug 2021

Cited by 4 | Viewed by 3392

Abstract

Psoriasis is a chronic skin disease affecting 2–3% of the global population. The proinflammatory IL-17A is a key cytokine in psoriasis. Accumulating evidence has revealed that IL-36γ plays also a pathogenic role. To understand more precisely the role of the IL-17A–IL-36γ cytokine network [...] Read more.

Psoriasis is a chronic skin disease affecting 2–3% of the global population. The proinflammatory IL-17A is a key cytokine in psoriasis. Accumulating evidence has revealed that IL-36γ plays also a pathogenic role. To understand more precisely the role of the IL-17A–IL-36γ cytokine network in skin pathology, we used an ear injection model. We injected IL-17A or IL-36γ alone and in combination into the ear pinnae of mice. This resulted in a significant increase in ear thickness measured over time. Histological evaluation of IL-17A + IL-36γ-treated skin showed a strong acanthosis, hyperparakeratosis and infiltration of neutrophils. The same histological features were found in mice after injection of IL-36γ alone, but to a lesser extent. IL-17A alone was not able to induce psoriasis-like changes. Genes encoding proteins of the S100 family, antimicrobial peptides and chemo-attractants for neutrophils were upregulated in the IL-17A + IL-36γ group. A much weaker expression was seen after the injection of each cytokine alone. These results strengthen the hypothesis that IL-17A and IL-36γ drive psoriatic inflammation via a synergistic interaction. Our established intradermal ear injection model can be utilized in the future to monitor effects of various inhibitors of this cytokine network. Full article

(This article belongs to the Special Issue Psoriasis: New Developments and Concepts in Pathogenesis and Treatment)

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10 pages, 1095 KiB

Open AccessArticle

Association of Nonalcoholic Hepatic Fibrosis with Body Composition in Female and Male Psoriasis Patients

by Kinga Brunner, Péter Oláh, Mehdi Moezzi, Gabriella Pár, Áron Vincze, Zita Breitenbach and Rolland Gyulai

Life 2021, 11(8), 763; https://doi.org/10.3390/life11080763 - 29 Jul 2021

Cited by 5 | Viewed by 2343

Abstract

Psoriasis has been associated with increased frequency of hepatic diseases. Psoriasis severity, obesity, insulin resistance, aspartate aminotransferase level, platelet count, and alcohol use are significant predictors for advanced fibrosis in psoriasis patients. Although psoriasis patients also present body composition changes (e.g., higher overall [...] Read more.

Psoriasis has been associated with increased frequency of hepatic diseases. Psoriasis severity, obesity, insulin resistance, aspartate aminotransferase level, platelet count, and alcohol use are significant predictors for advanced fibrosis in psoriasis patients. Although psoriasis patients also present body composition changes (e.g., higher overall body fat, visceral fat and sarcopenia), and these have recently been reported as risk factors for hepatic fibrosis, to date, body composition has not been prospectively investigated in psoriasis in the context of liver fibrosis. In this study anthropometric assessment (body weight and body mass index (BMI)), body composition analysis (body fat%, visceral fat scores and muscle mass%), and liver stiffness measurements (using transient elastography [TE]) were done in 52 psoriasis patients undergoing methotrexate therapy. Fourteen patients (26.9%) had advanced (F3–F4) liver fibrosis. There was no correlation between the patients’ liver stiffness values and the cumulative MTX doses. On the other hand, patients with higher BMI values, total body fat% and visceral fat scores were significantly more likely to present with higher hepatic stiffness values. BMI was a significant predictor of hepatic fibrosis in both genders. In males, body fat% (R = 0.578, p = 0.002) and, especially, visceral fat scores (R = 0.716, p < 0.001) had statistically significant correlation with stiffness scores, while in females only visceral fat scores were statistically significant predictors of the liver stiffness values (R = 0.452, p = 0.023), and body fat% was not (R = 0.187, p = 0.382). Our results suggest that anthropometric data should be assessed differently in female and male psoriasis patients when evaluating liver fibrosis risk. Full article

(This article belongs to the Special Issue Psoriasis: New Developments and Concepts in Pathogenesis and Treatment)

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9 pages, 720 KiB

Open AccessArticle

Genetic Investigation of Inverse Psoriasis

by Anikó Göblös, Emese Varga, Katalin Farkas, Kristóf Árvai and Lajos Kemény

Life 2021, 11(7), 654; https://doi.org/10.3390/life11070654 - 5 Jul 2021

Cited by 5 | Viewed by 13423

Abstract

Inverse psoriasis is considered to be a rare variant of plaque-type psoriasis and is associated with significantly impaired quality of life. Clinical manifestations and treatment options are somewhat different for each subtype. Identifying genetic variants that contribute to the susceptibility of different types [...] Read more.

Inverse psoriasis is considered to be a rare variant of plaque-type psoriasis and is associated with significantly impaired quality of life. Clinical manifestations and treatment options are somewhat different for each subtype. Identifying genetic variants that contribute to the susceptibility of different types of psoriasis might improve understanding of the etiology of the disease. Since we have no current knowledge about the genetic background of inverse psoriasis, whole exome sequencing was used to comprehensively assess genetic variations in five patients with exclusively inverse lesions. We detected six potentially pathogenic rare (MAF < 0.01) sequence variants that occurred in all investigated patients. The corresponding mutated genes were FN1, FBLN1, MYH7B, MST1R, RHOD, and SCN10A. Several mutations identified in this study are known to cause disease, but roles in psoriasis or other papulosquamous diseases have not previously been reported. Interestingly, potentially causative variants of established psoriasis-susceptibility genes were not identified. These outcomes are in agreement with our hypothesis that the inverse subtype is a different entity from plaque-type psoriasis. Full article

(This article belongs to the Special Issue Psoriasis: New Developments and Concepts in Pathogenesis and Treatment)

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10 pages, 511 KiB

Open AccessArticle

Study of Skin Barrier Function in Psoriasis: The Impact of Emollients

by Daniel Maroto-Morales, Trinidad Montero-Vilchez and Salvador Arias-Santiago

Life 2021, 11(7), 651; https://doi.org/10.3390/life11070651 - 4 Jul 2021

Cited by 25 | Viewed by 4949

Abstract

Psoriasis is a chronic multi-systemic inflammatory disease that affects the epidermal barrier. Emollients can be used as a coadjutant therapy for psoriasis management, but little is known about how the epidermal barrier function in psoriatic patients is modified by moisturizers. The objective of [...] Read more.

Psoriasis is a chronic multi-systemic inflammatory disease that affects the epidermal barrier. Emollients can be used as a coadjutant therapy for psoriasis management, but little is known about how the epidermal barrier function in psoriatic patients is modified by moisturizers. The objective of this study is to evaluate the effect of Vaseline jelly and a water-based formula on epidermal barrier function in psoriatic patients. Thirty-one patients with plaque-type psoriasis and thirty-one gender and age-matched healthy controls were enrolled in the study. Temperature, transepidermal water loss (TEWL), stratum corneum hydration (SCH), pH, elasticity and the erythema index were measured using non-invasive tools before and after applying Vaseline jelly and a water-based formula. TEWL was higher in psoriatic plaques than uninvolved psoriatic skin (13.23 vs. 8.54 g·m⁻²·h⁻¹; p < 0.001). SCH was lower in psoriatic plaques than uninvolved psoriatic skin and healthy skin (13.44 vs. 30.55 vs. 30.90 arbitrary units (AU), p < 0.001). In psoriatic plaques, TEWL decreased by 5.59 g·m⁻²·h⁻¹ (p = 0.001) after applying Vaseline Jelly, while it increased by 3.60 g·m⁻²·h⁻¹ (p = 0.006) after applying the water-based formula. SCH increased by 9.44 AU after applying the water-based formula (p = 0.003). The use of emollients may improve epidermal barrier function in psoriatic patients. TEWL is decreased by using Vaseline, and SCH is increased by using the water-based formula. Full article

(This article belongs to the Special Issue Psoriasis: New Developments and Concepts in Pathogenesis and Treatment)

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10 pages, 898 KiB

Open AccessArticle

A New Classification of the Severity of Psoriasis: What’s Moderate Psoriasis?

by Laura Salgado-Boquete, José Manuel Carrascosa, Mar Llamas-Velasco, Ricardo Ruiz-Villaverde, Pablo de la Cueva and Isabel Belinchón

Life 2021, 11(7), 627; https://doi.org/10.3390/life11070627 - 29 Jun 2021

Cited by 20 | Viewed by 5312

Abstract

The purpose of this study is to propose a ranking system for the severity of psoriasis. The consensus method of selecting the indices to include and the classification of real patient profiles by an expert panel to create a gold standard of severity [...] Read more.

The purpose of this study is to propose a ranking system for the severity of psoriasis. The consensus method of selecting the indices to include and the classification of real patient profiles by an expert panel to create a gold standard of severity were used. The performance of potential cut-offs was evaluated to create a ranking algorithm. The combined use of PASI, BSA, and sPGA may allow the classification of the severity of psoriatic patients. The final algorithm identifies severe patients in a single step (2 out 3 are met: PASI ≥ 11 or BSA ≥ 10 or sPGA ≥ 3), while two steps are required for mild ((2 out 3 are met: PASI ≤ 3 or BSA ≤ 5 or sPGA ≤ 2) and DLQI < 5) and moderate forms (the patient does not meet 2 out 3 (PASI ≥ 11 or BSA ≥ 10 or sPGA ≥ 3) but has a DLQI ≥ 5. A ranking algorithm is presented, consisting of different measures of disease which classifies psoriatic patients into three categories: mild, moderate, and severe. Full article

(This article belongs to the Special Issue Psoriasis: New Developments and Concepts in Pathogenesis and Treatment)

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11 pages, 271 KiB

Open AccessArticle

Characteristics of Pruritus in Various Clinical Variants of Psoriasis: Results of the Multinational, Multicenter, Cross-Sectional Study

by Kamila Jaworecka, Dominika Kwiatkowska, Luiza Marek, Funda Tamer, Aleksandra Stefaniak, Magdalena Szczegielniak, Joanna Chojnacka-Purpurowicz, Monika Matławska, Ayla Gulekon, Jacek C. Szepietowski, Joanna Narbutt, Agnieszka Owczarczyk-Saczonek and Adam Reich

Life 2021, 11(7), 623; https://doi.org/10.3390/life11070623 - 27 Jun 2021

Cited by 10 | Viewed by 3443

Abstract

Psoriasis is a chronic, inflammatory skin disease present in about 3% of the world’s population. The clinical symptoms manifest diversely, therefore one can distinguish several subtypes of psoriasis. The majority of patients with psoriasis experience pruritus, which is an unpleasant sensation that decreases [...] Read more.

Psoriasis is a chronic, inflammatory skin disease present in about 3% of the world’s population. The clinical symptoms manifest diversely, therefore one can distinguish several subtypes of psoriasis. The majority of patients with psoriasis experience pruritus, which is an unpleasant sensation that decreases patients’ quality of life. The knowledge on pruritus in different subtypes of psoriasis is limited. We have performed a cross-sectional, prospective, and multicenter study to evaluate the relationship between clinical subtypes of psoriasis (large-plaque, nummular, guttate, palmoplantar, inverse, erythrodermic, palmoplantar pustular, generalized pustular psoriasis, and psoriasis of the scalp) and the prevalence, intensity, and clinical manifestation of itch. We introduced a questionnaire assessing various aspects of pruritus to a total of 254 patients. Out of these, 42 were excluded. Pruritus was present in 92.9% of the remaining patients and its prevalence did not depend on the clinical subtype. A correlation between the severity of psoriasis and the intensity of itch was explicitly noticeable in palmoplantar pustular psoriasis and scalp psoriasis (p < 0.05). The itch sensation was individual and differed among subtypes of psoriasis. In conclusion, pruritus is a frequent phenomenon, and its presentation is different in various subtypes of psoriasis. Full article

(This article belongs to the Special Issue Psoriasis: New Developments and Concepts in Pathogenesis and Treatment)

14 pages, 3030 KiB

Open AccessArticle

Stress-Related Regulation Is Abnormal in the Psoriatic Uninvolved Skin

by Renáta Bozó, Judit Danis, Lili Borbála Flink, Dániel László Vidács, Lajos Kemény and Zsuzsanna Bata-Csörgő

Life 2021, 11(7), 599; https://doi.org/10.3390/life11070599 - 23 Jun 2021

Cited by 6 | Viewed by 2271

Abstract

Keratinocyte stress-response of the uninvolved psoriatic epidermis is known to be altered compared to healthy cells. Therefore, we aimed to reveal potential mechanisms underlying this alteration. We compared the expression of annotated cell-stress-related proteins between uninvolved psoriatic and healthy skin using the protein [...] Read more.

Keratinocyte stress-response of the uninvolved psoriatic epidermis is known to be altered compared to healthy cells. Therefore, we aimed to reveal potential mechanisms underlying this alteration. We compared the expression of annotated cell-stress-related proteins between uninvolved psoriatic and healthy skin using the protein array method. Data were analyzed by the Reactome over-representation test. We found that p27/CDKN1B and cytochrome C showed at least a two-fold increase, while cyclooxygenase-2, indolamine-2,3-dioxygenase-1, serum paraoxonase 1, serum paraoxonase 3, serine-46-phosphorylated tumor protein p53, and superoxide-dismutase-2 showed a two-fold decrease in expression in the uninvolved skin. Over-representation analysis suggested the Forkhead-box protein O (FOXO)-mediated transcription as the most significant pathway affected by the differently expressed cell-stress-related proteins (DECSRPs). DECSRPs indicate increased FOXO-mediated transcription of cell-cycle genes and reduced interleukin-signaling in the psoriatic uninvolved skin. Nuclear positivity of the FOXO-signaling-related p27/CDKN1B and FOXO1 are negatively correlated with the disease severity and showed increased expression in the uninvolved epidermis and also in healthy primary keratinocytes, which were grown on cartilage oligomeric matrix protein-coated surfaces. Our results indicate a cell-cycle inhibitory process, as a stress-related compensatory mechanism in the uninvolved epidermis, that could be responsible for blocking keratinocyte hyperproliferation in the psoriatic uninvolved skin, thus maintaining the symptomless skin phenotype. Full article

(This article belongs to the Special Issue Psoriasis: New Developments and Concepts in Pathogenesis and Treatment)

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12 pages, 294 KiB

Open AccessArticle

Anti-Interleukin-17 Therapy of Severe Psoriatic Patients Results in an Improvement of Serum Lipid and Inflammatory Parameters’ Levels, but Has No Effect on Body Composition Parameters

by Éva Anna Piros, Ákos Szabó, Fanni Rencz, Valentin Brodszky, Norbert Wikonkál, Pál Miheller, Miklós Horváth and Péter Holló

Life 2021, 11(6), 535; https://doi.org/10.3390/life11060535 - 9 Jun 2021

Cited by 10 | Viewed by 2732

Abstract

BACKGROUND: Psoriasis is frequently accompanied by metabolic syndrome. Effect of anti-tumor necrosis factor therapies on increases in body weight is well-known. Data on the effects of interleukin-17 inhibitors are limited. Authors determined the effect of anti-interleukin-17 therapies on the body composition and serum [...] Read more.

BACKGROUND: Psoriasis is frequently accompanied by metabolic syndrome. Effect of anti-tumor necrosis factor therapies on increases in body weight is well-known. Data on the effects of interleukin-17 inhibitors are limited. Authors determined the effect of anti-interleukin-17 therapies on the body composition and serum lipid and inflammatory parameters among severe psoriatic patients. METHODS: Thirty-five severe psoriatic patients were enrolled. Twenty-two received secukinumab and 13 received ixekizumab as their 2nd-or 3rd-line biological treatment. Before treatment initiation and 6 months later, laboratory examinations measuring metabolic and inflammatory panels and body composition analyses were performed. RESULTS: After 6 months, a significant reduction was observed in psoriasis area severity index (p < 0.001) from 18 to 0, in c-reactive protein (p < 0.001) from 6.6 to 4.00 mg/L, in low-density lipoprotein-cholesterol (p = 0.004) from 3.69 to 3.19 mmol/L, and an improvement in high-density lipoprotein-cholesterol (p = 0.022) from 1.31 to 1.40 mmol/L. Median baseline body mass index was 32.80 kg/m². The body composition parameters did not show any significant changes. CONCLUSIONS: Anti-interleukin-17 therapy of severe psoriatic patients does not cause significant changes in body composition parameters. Improvements in the lipid and inflammatory parameters might have a beneficial effect on patients’ cardiometabolic status. This effect might be detectable in high-risk obese psoriatic patients. Full article

(This article belongs to the Special Issue Psoriasis: New Developments and Concepts in Pathogenesis and Treatment)

Review

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11 pages, 265 KiB

Open AccessReview

Psoriasis Therapy and Skin Cancer: A Review

by Beatriz Butrón-Bris, Esteban Daudén and Pedro Rodríguez-Jiménez

Life 2021, 11(10), 1109; https://doi.org/10.3390/life11101109 - 19 Oct 2021

Cited by 24 | Viewed by 3242

Abstract

Introduction: psoriasis is a chronic immune-mediated disease that is associated with several comorbidities, including an increased risk of malignancies, particularly skin cancer. A large number of studies have investigated whether psoriasis itself, psoriasis-associated comorbidities, or psoriasis treatment could lead to an increased risk [...] Read more.

Introduction: psoriasis is a chronic immune-mediated disease that is associated with several comorbidities, including an increased risk of malignancies, particularly skin cancer. A large number of studies have investigated whether psoriasis itself, psoriasis-associated comorbidities, or psoriasis treatment could lead to an increased risk of neoplasms. Methods: we reviewed the literature using the most important databases (PubMed, MEDLINE, ETHERIA). All articles pertaining to skin cancer associated with psoriasis disease and psoriasis therapy were included. In this review, we also discuss some of the potential underlying mechanisms for these associations, particularly regarding the multiple psoriasis therapies currently available, and their possible implications in higher incidences of skin cancer in these patients. Conclusion: evidence suggests that these patients might have a higher risk of cutaneous malignancies, especially for NMSC, compared with psoriasis-free patients. The reasons for this increased risk remain to be determined. However, high dose PUVA therapy, the immunosuppressive treatments used, and the comorbidities and habits frequently described in these patients seem to play a role in the pathogenesis of these tumors. Because of these facts, periodic screening for skin cancer is recommended in this population. Full article

(This article belongs to the Special Issue Psoriasis: New Developments and Concepts in Pathogenesis and Treatment)

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