Psoriatic Skin Lesions Research Articles

Dietary olive oil intake aggravates psoriatic skin inflammation in mice via Nrf2 activation and polyunsaturated fatty acid imbalance

Psoriasis is a chronic inflammatory skin disease, which does not have effective treatment options. However, olive oil has been suggested as an alternative to treat psoriasis, but no study has evaluated the mechanisms involved in the effects of olive oil on psoriasis. Thus, the current study investigated whether olive oil could ameliorate psoriasiform skin inflammation. To test this, mice received topical application of imiquimod to induce inflammation and were treated orally with olive oil. Human immortalized keratinocytes were also treated with imiquimod and olive oil. Epidermal thickness and keratinocyte proliferation were increased in imiquimod-induced lesions of olive-oil-treated animals. In both in vitro and in vivo studies, protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) were elevated following imiquimod and olive oil administration. Inhibition of Nrf2 abolished the increased proliferation of keratinocytes treated with imiquimod and olive oil, demonstrating the role of Nrf2 in olive oil-mediated exacerbation of psoriasiform skin inflammation. In addition, lower levels of linoleic acid and higher levels of oleic acid were observed in imiquimod- and olive-oil-treated animals, which may also contribute to the adverse effects of olive oil on psoriasis. In conclusion, dietary intake of olive oil aggravates the symptoms of psoriatic skin lesions through the overexpression of Nrf2 and an imbalance in oleic and linoleic acids levels, suggesting that a diet rich in olive oil may have significant negative effects on psoriasis.

CHRNA5 Is Overexpressed in Patients with Psoriasis and Promotes Psoriasis-Like Inflammation in Mouse Models

It is well known that psoriasis is closely related to smoking, and CHRNA5 plays an important role in smoking-related diseases. However, studies on the relationship between CHRNA5 and psoriasis are limited. This study aimed to examine the role of CHRNA5 in psoriasis development and pathogenesis. Analysis in psoriatic tissues and imiquimod-induced mouse models showed that CHRNA5 was highly expressed in psoriatic lesional skin. To further verify the function of CHRNA5, we constructed Chrna5-knockout mice and induced the psoriasis model. We found that Chrna5 knockout significantly reduced the severity of psoriasis and could regulate inflammation through the MAPK kinase kinase-1/c-Jun N-terminal kinase‒MAPK/NF-κB pathway. The single-cell sequencing results revealed that after Chrna5 knockout, the keratinocyte subpopulation was significantly reduced and the related Jak/signal transducer and activator of transcription signaling pathway was downregulated, further indicating the importance of CHRNA5 in psoriasis. Human keratinocytes were analyzed, and silencing CHRNA5 inhibited keratinocyte proliferation and migration. In summary, CHRNA5 played important roles in the development and pathogenesis of psoriasis, and targeting CHRNA5 may be an effective strategy for the treatment of psoriasis.

COVID-19 in Patients with Psoriatic Arthritis

The COVID-19 pandemic has a negative impact on all aspects of human life and can lead to the exacerbation of chronic diseases. At the same time, it is known that a higher risk of infection and a more severe course of coronavirus infection is found in the elderly, as well as in people with serious comorbidities. Psoriatic arthritis (PsA) is a type of inflammatory arthritis that is often diagnosed in patients with psoriasis. Specific treatment of patients with chronic inflammatory joint disease include nonsteroidal anti-inflammatory drugs, glucocorticosteroids, disease-modifying antirheumatic drugs, new biological agents, including monoclonal antibodies to IL-6, IL-1, TNF-a, target disease modifying drugs. Medications used for PsA treatment can potentially have both negative and positive effects on the course of COVID-19. The objective: to analyze the features of COVID-19 in patients with PsA and to study the comorbid pathology after coronavirus infection. Materials and methods. The study involved 174 people with a verified diagnosis of PsA. Patients were divided into two groups. Group I included 112 (64.4%) persons who had COVID-19, and group II - 62 (35.6%) who had not had coronavirus infection at the time of first examination. Patients in group I significantly differed from group II in age (p <0.001) and duration of PsA (p <0.001), showed a significantly higher degree of psoriatic skin lesions and activity of the underlying disease (p = 0.001) compared to patients from group II. The participants of the study underwent examination characterize the course of the psoriatic disease and skin lesions and risk of cardiovascular disease. Results. To date, there are no clear scientific data that reveal the specific features of COVID-19 infection and the effect of antirheumatic therapy on the development of dangerous complications associated with coronavirus infection in patients with PsA. The analysis of comorbid pathology has found cardiovascular pathology in 67 (59.8%) of patients, including arterial hypertension – in 58 (51.8%) people, metabolic syndrome – in 34 (30.4%), diseases of the digestive system – in 32 (28.6%) and respiratory system – in 24 (21.4%) of persons. Conclusions. Patients with higher activity and duration of the PsA were significantly more likely to get COVID-19 and demonstrated higher total cardiovascular risk for the next 10 years. Further research is needed to study the impact of specific basic rheumatological drugs on the outcomes of COVID-19 and to analyze the broader effects of the pandemic on the course of psoriatic arthritis.

Efficacy of calcipotriol plus betamethasone dipropionate foam on psoriatic skin lesions beyond human eyes: An observational study.

Background and AimsCalcipotriol plus betamethasone dipropionate foam has been developed as a new topical therapeutic option for psoriasis, whose effect has been documented mainly on clinical basis.MethodsWe decided to evaluate its efficacy on 11 patients, not only at the clinical level (by using Psoriasis Area Severity Index [PASI], Dermatology Life Quality Index [DLQI], and Psoriasis Global Assessment [PGA] clinimetric indexes) but especially from a subclinical viewpoint (by using videocapillaroscopy and thermography).ResultsAfter 4 weeks of treatment with calcipotriol plus betamethasone dipropionate foam, there was a marked reduction in all three clinimetric indixes PASI, PGA, and DLQI (DLQI mean value decreased from 13.45 ± 3.59 to 6.82 ± 3.31 (p = 0.001), PASI from 7.909 ± 2.857 to 4.582 ± 2.422 (p = 0.001), PGA from 1.8 ± 0.6 to 0.7 ± 0.4 (p = 0.002). From thermographic survey, a significant reduction of mean value of ΔT (temperature difference [°C] between center of the lesions and their periphery [healthy skin]), from 0.28 ± 0.99 to −0.42 ± 0.39 (p = 0.058), was observed. An exceptional reduction of capillaries of psoriatic plaques was detected through videocapillaroscopy (capillary density decreased from 27.91 ± 6.70 capillaries/mm2 to 4.54 ± 2.77 capillaries/mm2 (p = 0.001), with an 83.73% reduction).ConclusionOur results demonstrate both clinical and subclinical efficacy of calcipotriol plus betamethasone dipropionate foam on psoriatic skin lesions. The subclinical improvement detected, not only demonstrates that the therapeutic effect of foam is truly due to a decrease in inflammation, but, being earlier and more effectively detectable than clinical benefit, suggests future applications of thermography and videocapillaroscopy in evaluating the in vivo effect of therapies for psoriasis, and, in general, the course of the disease “beyond human eyes.”

Precision treatment of Singleton Merten syndrome with ruxolitinib: a case report

BackgroundSingleton-Merten syndrome 1 (SGMRT1) is a rare type I interferonopathy caused by heterozygous mutations in the IFIH1 gene. IFIH1 encodes the pattern recognition receptor MDA5 which senses viral dsRNA and activates antiviral type I interferon (IFN) signaling. In SGMRT1, IFIH1 mutations confer a gain-of-function which causes overactivation of type I interferon (IFN) signaling leading to autoinflammation.Case presentationWe report the case of a nine year old child who initially presented with a slowly progressive decline of gross motor skill development and muscular weakness. At the age of five years, he developed osteoporosis, acro-osteolysis, alveolar bone loss and severe psoriasis. Whole exome sequencing revealed a pathogenic de novo IFIH1 mutation, confirming the diagnosis of SGMRT1. Consistent with constitutive type I interferon activation, patient blood cells exhibited a strong IFN signature as shown by marked up-regulation of IFN-stimulated genes. The patient was started on the Janus kinase (JAK) inhibitor, ruxolitinib, which inhibits signaling at the IFN-α/β receptor. Within days of treatment, psoriatic skin lesions resolved completely and the IFN signature normalized. Therapeutic efficacy was sustained and over the course muscular weakness, osteopenia and growth also improved.ConclusionsJAK inhibition represents a valuable therapeutic option for patients with SGMRT1. Our findings also highlight the potential of a patient-tailored therapeutic approach based on pathogenetic insight.

Narrowband-UVB treatment reduces levels of mediators of the Th17 pathway and chemotaxis in psoriatic skin without any concurring effect on mediator levels in serum

Narrowband-UVB (NB-UVB) is a common and effective psoriasis treatment. It exerts its effect locally and is therefore a better model for exploring dynamics of serum biomarkers reflecting psoriasis skin disease activity compared to other treatments with systemic uptake. To perform an exploratory study to assess potential roles of multiple disease mediators as biomarkers for psoriasis disease activity, and increase understanding of NB-UVB treatment effects in psoriatic skin. Patients with plaque psoriasis were sampled (lesional, non-lesional skin, serum) before and after full NB-UVB treatment. Samples were assessed for 78 different mediators using Luminex assays. Correlation networks were analysed to explore interactions between lesional skin mediators before and after NB-UVB treatment. None of the studied serum mediators were significantly affected by NB-UVB treatment after correction for multiple testing. Thirty mediators revealed a significant difference in lesional skin compared to non-lesional skin before treatment including interleukin 23 (IL-23) and C-C motif chemokine ligand 20 (CCL20), but also novel mediators such as angiopoietin-like 4 (ANGPTL4) and pentraxin 3 (PTX3). The levels of 25 mediators in skin decreased significantly, and network analysis revealed markedly reduced cluster formations and correlations after NB-UVB. NB-UVB treatment reduced the concentration of mediators of the Th17 inflammatory pathway and chemotaxis in psoriatic lesional skin, but also affected less studied and novel mediators. Although the treatment affected the levels of a majority of mediators in skin, no corresponding effect was observed in serum, thus challenging the possibility of a serum biomarker reflecting skin disease activity.

Alpha-7 nicotinic acetylcholine receptor agonist alleviates psoriasis-like inflammation through inhibition of the STAT3 and NF-\u03baB signaling pathway

Psoriasis is a chronic inflammatory cutaneous disease; it has been discovered that stimulation of the nervous system increases susceptibility to psoriasis. Although the cholinergic anti-inflammatory pathway, which is mediated by the alpha-7 nicotinic acetylcholine receptor (α7nAChR), is critical for controlling multiple types of inflammation, its expression pattern and pathogenesis function in psoriatic lesioned skin tissue are unknown. We hereby analyzed the expression of α7nAchR in human and mouse psoriatic skin tissue. In vivo, PNU-282987 or Methyllycaconitine, a specific agonist or antagonist of α7nAchR, were administered to imiquimod (IMQ)-induced psoriatic mouse models. The macroscopic appearance and histopathological features of the psoriatic mice skin were evaluated. In addition, cell proliferation and differentiation markers were investigated. The level of pro-inflammatory cytokines released from the lesioned skin, as well as the activation of the relevant signaling pathways, were measured. Our findings indicated that psoriatic lesional skin expressed an increased level of α7nAChR, with its tissue distribution being primarily in skin keratinocytes and macrophages. In an IMQ-induced murine psoriasis model, α7nAChR agonist PNU-282987 treatment alleviated psoriasis-like inflammation by down-regulating the expression of multiple types of pro-inflammatory mediators and normalized keratinocyte proliferation and differentiation, whereas α7nAChR antagonist treatment exacerbated its effect. Mechanically, we observed that activation of the α7nAChR inhibited the activation of the STAT3 and NF-κB signaling pathways in in vitro cultured HaCaT cells induced by Th17-related cytokine IL-6/IL-22 or Th1-related cytokine TNF-α. Taken together, these findings demonstrate that attenuation of psoriatic inflammation via the cholinergic anti-inflammatory pathway is dependent on α7nAChR activation.

OAS1, OAS2, and OAS3 Contribute to Epidermal Keratinocyte Proliferation by Regulating Cell Cycle and Augmenting IFN-1‒Induced Jak1‒Signal Transducer and Activator of Transcription 1 Phosphorylation in Psoriasis

Psoriasis is a systemic immune‒mediated inflammatory disease characterized by hyperproliferation and abnormal differentiation of epidermal keratinocytes. Recent studies have identified IL-17 and IL-23 as key drivers of psoriasis pathogenesis, but the underlying molecular mechanisms remain unclear. The 2'-5'-oligoadenylate synthetases (OASs), namely, OAS1, OAS2, OAS3, and OASL, are a family of IFN-induced enzymes with multiple antiviral activities, but their role in psoriasis is unknown. In this study, we identified the overexpression of OAS1, OAS2, and OAS3 in human lesional psoriatic skin and serum and found that their expression was downregulated by biologics. Moreover, OASs were highly expressed in epidermal keratinocytes, epidermal dendritic cells, epidermal CD3+ T cells, dermal antigen-presenting cells, and dermal T cells from the psoriatic epidermis and dermis, as determined by flow cytometry. In addition, OASs were upregulated by poly(I:C), poly(dA:dT), and IFN-1s but downregulated by Jak inhibitors in normal human epidermal keratinocytes. Furthermore, silencing of OASs inhibited the phosphorylation of Jak1 and signal transducer and activator of transcription 1. Knockdown of OASs suppressed keratinocyte proliferation by inhibiting cell cycle progression. Thus, OASs may be therapeutic biomarkers in psoriasis.

T-cell receptor sequencing specifies psoriasis as a systemic and atopic dermatitis as a skin-focused, allergen-driven disease.

Atopic dermatitis (AD) and psoriasis represent two of the most common inflammatory skin diseases in developed countries. A hallmark of both diseases is T-cell infiltration into the skin. However, it is still not clarified to what extent these infiltrating T cells are antigen-specific skin-homing T cells or unspecific heterogeneous bystander cells. To elucidate this, T cells from lesional skin and from blood of 9 AD and 10 psoriasis patients were compared by receptor (TCR) sequencing. Therefore, peripheral blood mononuclear cells (PBMC) were cell-sorted according to expression of the cutaneous leukocyte antigen (CLA) into skin-homing (CLA+ ) and non-skin-homing (CLA- ) subfractions. Aeroallergen-specific T-cell lines were grown from AD patients' PBMC in parallel. Intra-individual comparison of TCRB CDR3 regions revealed that clonally expanded T cells in skin lesions of both AD and psoriasis patients corresponded to skin-homing circulating T cells. However, in psoriasis patients, these T-cell clones were also detectable to a larger extent among CLA- circulating T cells. Up to 28% of infiltrating cells in AD skin were identified as allergen-specific by overlapping TCR sequences. Our data show that in line with the systemic nature of psoriasis, T-cell clones that infiltrate psoriatic skin lesions do not exclusively possess skin-homing ability and are therefore most probably specific to antigens that are not exclusively expressed or located in the skin. T cells driving AD skin inflammation appear to home nearly exclusively to the skin and are, to a certain extent, specific to aeroallergens.

Prospects for the use of monoclonal antibodies to interleukin 23 Gusеlkumab in psoriatic arthritis: New data

Among the pathophysiological mechanisms of immune-mediated inflammatory diseases (IMIDs), specific attention has been paid to the abnormal activation of Th17 type immune response related to the dysregulated synthesis of cytokines forming the interleukin (IL)-23 and IL-17 axis. IL-23 blockade is an innovative approach to the treatment of psoriasis and psoriatic arthritis (PsA). Much of the interest has focused on guselkumab (GUS) (TREMFYA, Janssen, Johnson & Johnson, USA), a fully human IgG λ monoclonal antibody (mAb) targeting the p19 IL-23 subunit and the first-in-class treatment approved for patients with psoriasis and PsA. In patients with psoriasis, GUS is at least as effective as other biologic therapies for PsA and is superior to ustekinumab, an anti-IL-12/IL-23 mAb, and secukinumab, an anti-IL-17 mAb. Compared with TNF-α inhibitors, GUS therapy is less likely to cause infections and does not increase the risk of the reactivation of latent TB infection. The new GRAPPA guidelines (2021) recommend GUS (and other IL-23 inhibitors) for patients with PsA resistant to conventional disease-modifying antirheumatic drugs (DMARDs), who have peripheral arthritis, enthesitis, dactylitis, psoriatic skin and nail lesions. The paper discusses new data on the efficacy of GUS in patients resistant to TNF-α inhibitors, its benefits in patients with axial PsA, and safety during the COVID-19 pandemic.

Psoriatic Skin Lesions after Apalutamide Treatment.

Abstract is missing (Short communication)

Alantolactone-loaded chitosan/hyaluronic acid nanoparticles suppress psoriasis by deactivating STAT3 pathway and restricting immune cell recruitment

Psoriasis is a common chronic immune-mediated skin disease characterized by hyperproliferation and aberrant differentiation of keratinocytes and massive infiltration of inflammatory immune cells. Recent studies showed that Signal Transducer and Activator of Transcription 3 (STAT3), which plays an important role in cell survival, proliferation, differentiation, angiogenesis, and immune responses, is constitutively activated in epidermal keratinocytes of human psoriatic skin lesions. In addition, STAT3 promotes the differentiation and expansion of T cells and facilitates cytokine production, thereby exacerbating the condition of psoriasis. Alantolactone (ALT) is a sesquiterpene lactone compound that could selectively suppress STAT3 activation, but its effectiveness and application in psoriasis treatment have not been determined. In this study, we developed ALT loaded chitosan/hyaluronic acid nanoparticles (CHALT), and investigated its therapeutic potential for psoriasis therapy. CHALT effectively abrogated the hyperproliferation by inducing ROS-mediated apoptosis with loss of mitochondrial membrane potential, and also inhibited IL-6-induced STAT3 signaling activation and inflammatory reaction in HaCaT cell line. In an Imiquimod (IMQ)-induced psoriasis model, the topical treatment of psoriasis lesions with CHALT effectively attenuated the STAT3 hyperactivation within keratinocytes and ameliorated the symptoms of psoriasis. In addition, it was found that CHALT restricted the recruitment of immune cells. These results indicated that ALT-based nanoformulation CHALT holds great potential for psoriasis therapy.

Impact of Adalimumab Treatment on Interleukin-17 and Interleukin-17 Receptor Expression in Skin and Synovium of Psoriatic Arthritis Patients with Mild Psoriasis.

Interleukin (IL)-17 and tumor necrosis factor-alpha (TNF)-α are key players in psoriatic arthritis (PsA) pathogenesis. While both cytokines can be therapeutically targeted with beneficial clinical outcome, it is unclear whether inhibiting one cytokine will affect the other at sites of inflammation. If both act independently, this might provide a rationale for dual or combined inhibition of both cytokines. Here, we evaluated the effect of TNF blockade in PsA patients on IL-17 levels in both skin and synovial tissue biopsies. PsA patients with mild psoriatic skin lesions were randomized to receive either adalimumab or placebo for four weeks. Synovial and skin biopsies were obtained at weeks zero and four. Skin from healthy donors (HDs) was used for comparison. Expression of IL-17A, IL-17F, IL-17RA and IL-17RC was assessed by immunohistochemistry and analyzed with digital image analysis. We found relatively low levels of IL-17 and its receptors in the skin of PsA patients compared to HD, and only IL-17F in the dermis of lesional psoriatic skin was significantly higher compared to HD skin (p = 0.0002). Histologically IL-17A, IL-17F, IL-17RA and IL-17RC in skin and synovial tissue were not downregulated by adalimumab treatment. Thus, in this cohort of PsA patients with mild psoriasis, TNF blockade did not affect the protein levels of IL-17 cytokines and its receptors in skin and synovium, despite reduced cellular inflammation and improved clinical outcome for joint involvement.

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

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.

MicroRNA-17-3p is upregulated in psoriasis and regulates keratinocyte hyperproliferation and pro-inflammatory cytokine secretion by targeting CTR9.

Psoriasis is a chronic inflammatory skin disease. Although miRNAs are reported to be associated with the pathogenesis of psoriasis, the contribution of individual microRNAs toward psoriasis remains unclear. The miR-17-92 cluster regulates cell growth and immune functions that are associated with psoriasis. miR-17-3p is a member of miR-17-92 cluster; however, its role in dermatological diseases remains unclear. Our study aims at investigating the effects of miR-17-3p and its potential target gene on keratinocytes proliferation and secretion of pro-inflammatory cytokine and their involvement in psoriasis. Initially, we found that miR-17-3p was upregulated in psoriatic skin lesions, and bioinformatic analyses suggested that CTR9 is likely to be a target gene of miR-17-3p. Quantitative reverse-transcriptase PCR and immunohistochemical analysis revealed that CTR9 expression was downregulated in psoriatic lesions. Using dual-luciferase reporter assays, we identified CTR9 as a direct target of miR-17-3p. Further functional experiments demonstrated that miR-17-3p promoted the proliferation and pro-inflammatory cytokine secretion of keratinocytes, whereas CTR9 exerted the opposite effects. Gain-of-function studies confirmed that CTR9 suppression partially accounted for the effects of miR- 17-3p in keratinocytes. Furthermore, Western blot revealed that miR-17-3p activates the downstream STAT3 signaling pathway while CTR9 inactivates the STAT3 signaling pathway. Together, these findings indicate that miR-17-3p regulates keratinocyte proliferation and pro-inflammatory cytokine secretion partially by targeting the CTR9, which inactivates the downstream STAT3 protein, implying that miR-17-3p might be a novel therapeutic target for psoriasis.

Expression Patterns of Clock Gene mRNAs and Clock Proteins in Human Psoriatic Skin Samples.

Psoriasis is a systemic inflammatory skin disorder that can be associated with sleep disturbance and negatively influence the daily rhythm. The link between the pathomechanism of psoriasis and the circadian rhythm has been suggested by several previous studies. However, there are insufficient data on altered clock mechanisms in psoriasis to prove these theories. Therefore, we investigated the expression of the core clock genes in human psoriatic lesional and non-lesional skin and in human adult low calcium temperature (HaCaT) keratinocytes after stimulation with pro-inflammatory cytokines. Furthermore, we examined the clock proteins in skin biopsies from psoriatic patients by immunohistochemistry. We found that the clock gene transcripts were elevated in psoriatic lesions, especially in non-lesional psoriatic areas, except for rev-erbα, which was consistently downregulated in the psoriatic samples. In addition, the REV-ERBα protein showed a different epidermal distribution in non-lesional skin than in healthy skin. In cytokine-treated HaCaT cells, changes in the amplitude of the bmal1, cry1, rev-erbα and per1 mRNA oscillation were observed, especially after TNFα stimulation. In conclusion, in our study a perturbation of clock gene transcripts was observed in uninvolved and lesional psoriatic areas compared to healthy skin. These alterations may serve as therapeutic targets and facilitate the development of chronotherapeutic strategies in the future.

The Impact of Hypertension, Diabetes, Lipid Disorders, Overweight/Obesity and Nicotine Dependence on Health-Related Quality of Life and Psoriasis Severity in Psoriatic Patients Receiving Systemic Conventional and Biological Treatment.

Psoriasis, a chronic disease, is associated with a higher prevalence of comorbidities and has negative impact on health-related quality of life (HRQOL). The objective was to investigate the effect of comorbidities on HRQOL, and psoriasis severity measured appropriately by the dermatology life quality index (DLQI) and the psoriasis area severity index (PASI) before, and after a 3-month treatment and the median DLQI or PASI reduction from baseline in the adult psoriatic patients receiving various types of treatment. The study included 184 adult plaque psoriatic patients. DLQI and PASI scores were assessed in the studied patients before the therapy (a baseline visit) and after a 3-month treatment (a control visit) depending on the presence of comorbidities. Psoriatic patients with comorbidities had worse HRQOL and more severe skin lesions. The presence of comorbidities had a negative effect on the outcome of treatment with the use of conventional therapy. The outcome of therapy with biological agents was independent of each of the analyzed factors. Biological treatment had a high effectiveness on the psoriatic skin lesions improvement despite the presence of comorbidities, whereas methotrexate was effective even if the patients had co-existing hypertension. In psoriatic patients receiving systemic conventional treatment but not biological treatment, comorbidities had a negative impact on HRQOL and psoriasis severity.

Immunohistochemical expression of cornulin in lesional and perilesional skin of plaque psoriasis

Psoriasis is an immune-related disease with dermal inflammation and epidermal hyperplasia. Cornulin has a significant role in keratinocyte proliferation and stimulates inflammation in psoriasis. This work aims to evaluate Cornulin expression values in lesional and perilesional psoriatic skin compared with the control group's skin through immunohistochemistry. This case-control study included 30 cases with plaque psoriasis and another 30 as controls. Patient samples were collected, and immunohistochemical staining of Cornulin was conducted. In the epidermis, there was a stepwise pattern of significant Cornulin overexpression in keratinocytes starting from controls (34.00±23.65) to lesional (62.59±23.93) passing through perilesional skin (36.52±18.49) (p<0.001). Moreover, there was also a stepwise pattern of the significance of Cornulin starting from 4 in controls (13.3% for both) to 28 lesional cases (93.3%) and 18 (60.0%) passing through 17 perilesional skin cases (56.7%) and 5 (16.7%) (p<0.001 for both) for inflammatory cells and adnexa, respectively. A significant relationship between lesional epidermal Cornulin's strong intensity and a higher H-score and both hyperkeratosis and parakeratosis was found (p=0.008 for both intensity and 0.028 for both H-scores). Cornulin might be implicated in keratinocyte hyperproliferation and inflammation in plaque psoriasis and may be valuable as therapeutic target.

Effect of Total Glucosides of Paeony on Imiquimod-Induced Psoriatic Skin Lesions by Regulating VEGF.

PurposeThe purpose of this study was to use a murine model of psoriasis to examine the effect of total glycosides of paeony (TGP) on psoriatic skin lesions and on the expression of vascular endothelial growth factor (VEGF) in skin lesions and blood.MethodsA murine model of psoriasis was produced by shaving the backs of the mice and applying 5% imiquimod cream, 50 mg, to the backs of the mice once a day. Mice were killed on day 8, and skin and blood samples were obtained for histopathological examination and analysis of VEGF mRNA expression.ResultsBy day 8 of the application of imiquimod cream, skin lesions characteristic of psoriasis were evident, and histopathological examination of skin sections showed changes consistent with psoriasis (corneum thickening and parakeratosis, attenuation of the stratum granulosum, thickening of the stratum spinosum, and lengthening of the epidermal ridge). In the treatment group, 7 days of treatment with TGP resulted in resolution of the skin lesions, and histopathological examination showed the epidermis and dermis are approximately normal, without corneum thickening, hyperkeratosis, and parakeratosis. On day 7 of treatment, skin expression of VEGF mRNA was significantly lower in the treatment group than in the group that did not receive treatment (p < 0.05). Blood VEGF mRNA expression was not different between the groups.ConclusionTGP is effective for the treatment of psoriasis and may act by decreasing lesion VEGF mRNA expression.

Noninvasive Tape-Stripping with High-Resolution RNA Profiling Effectively Captures a Preinflammatory State in Nonlesional Psoriatic Skin

Tape stripping is a minimally invasive, nonscarring method that can be utilized to assess gene expression in the skin but is infrequently used given technical constraints. By comparing different tape stripping technologies and full-thickness skin biopsy results of lesional and nonlesional psoriatic skin from the same patients, we demonstrate that tape stripping with optimized high-resolution transcriptomic profiling can be used to effectively assess and characterize inflammatory responses in the skin. Upon comparison with single-cell RNA-sequencing data from psoriatic full-thickness skin biopsies, we illustrate that tape-stripping efficiently captures the transcriptome of the upper layers of the epidermis with sufficient resolution to assess the molecular components of the feed-forward immune amplification pathway in psoriasis. Notably, nonlesional psoriatic skin sampled by tape stripping demonstrates activated, proinflammatory changes when compared to healthy control skin, suggesting a prepsoriatic state, which is not captured on full-thickness skin biopsy transcriptome profiling. This work illustrates an approach to assess inflammatory response in the epidermis by combining noninvasive sampling with high throughput RNA-sequencing, providing a foundation for biomarker discoveries and mechanism of action studies for inflammatory skin conditions.