Subtypes Of Psoriasis Research Articles

Psoriasis is a disease with several clinical presentations

Psoriasis is a common chronic inflammatory skin disease with several clinical subtypes. Recent discoveries in the genetics and immunology of the disease, particularly in plaque psoriasis, have revolutionised the treatment of patients with psoriasis. An understanding of the differences in genetics and immunology between different psoriasis subtypes is emerging. This review finds that the unraveling of the links between clinical presentation, genetics, immunology, treatment response, and comorbidities will allow for more individualised treatment of patients with psoriasis in the future.

Clinical course of psoriatic arthritis treated with biologics delineated with ultrasonography.

Psoriatic arthritis (PsA) is a chronic, inflammatory articular disease regarded as a specific subtype of psoriasis. Long-term assessment for PsA using ultrasonography has not yet been investigated. The present study was conducted to delineate the changes in articular lesions after the initiation of biologics using ultrasonography, and to provide the evidence of the utility of ultrasonography in long-term follow-up of PsA patients. We retrospectively recruited 17 Japanese PsA patients treated with biologics who met the classification criteria for psoriatic arthritis. Ultrasonographic images were recorded using a high-frequency linear 18 MHz probe through Doppler- and B-modes. Before the treatment with biologics, all examined patients (100%) had enthesitis and extensor tendinitis, while only six patients (35.3%) had loss of the fibrillar pattern of the tendon (LFP). There were significant changes over time in the numerical rating scale score for pain, and in the degree of ultrasonographic findings, including enthesitis, extensor tendinitis, and LFP. Also, there were significant changes over time between these ultrasonographic findings. The study identified the improvement course for a specific PsA lesion after the initiation of biologics. The improvement courses in enthesitis, extensor tendinitis, and LFP were found to differ from each other. These results may contribute to deeper understanding of the pathogenesis of PsA.

The risk of different subtypes of psoriasis following an episode of guttate psoriasis

The risk of different subtypes of psoriasis following an episode of guttate psoriasis

Naevoid Blaschkoid Psoriasis: A curable mosaic abnormalities of the skin.

Naevoid Blaschkoid Psoriasis is a rare and underdiagnosed subtype of linear psoriasis. Characteristic aspects of naevoid blaschkoid psoriasis include a late onset of asymptomatic erythematous and scaly plaques along with blaschko line. Here, we report on a patient with a delayed definitive diagnosis of mosaic pattern skin in early infancy, who experienced significant clearing of skin plaques after treatment with an interleukin 17 (IL-17) inhibitor (secukinumab). This case reminds clinicians to take psoriasis into consideration under the differential diagnosis of blaschkoid dermatoses.

New and Emerging Treatments for Generalized Pustular Psoriasis: Focus on IL-36 Receptor Inhibitors.

Generalized Pustular Psoriasis (GPP) is a rare and severe subtype of psoriasis that significantly impacts patients' quality of life. Until recently, no specific treatment modalities were available, and treatment for GPP followed the guidelines for the treatment of plaque psoriasis, consisting of conventional treatments, such as retinoids, methotrexate, and even biologics, which although effective in some cases, may be associated with significant side effects, necessitating more effective and safe options. The pathophysiology of Generalized Pustular Psoriasis is complex and not fully understood, but there is some overlap with the pathogenesis of Plaque Psoriasis. In GPP, the innate immune system seems to play a more significant role, with the interleukin (IL)-36 pathway being fundamentally involved. Spesolimab and imsidolimab, two recently developed therapeutic agents, target the IL-36 inflammatory pathway by binding to the IL-36 receptor (IL-36R). Both biologics have already been evaluated in phase 1 and 2 clinical trials and have shown promising results in terms of safety and efficacy. IL-36 receptor inhibitors demonstrated great efficacy and good safety profile in the management of patients with GPP, demonstrating their potential to emerge as a leading treatment option. This review aims to explore and summarize the current scientific literature on the most recently developed treatments for GPP.

Identification of angiogenesis-related genes and molecular subtypes for psoriasis based on random forest algorithm.

Psoriasis is a chronic immune-mediated recurrent skin disease causing systemic damage. Increased angiogenesis has been reported to participate in the progression of psoriasis. However, angiogenesis-related genes (ARGs) in psoriasis have not been systematically elucidated. Therefore, we aim to identify potential biomarkers and subtypes using two algorithmsr. Transcriptome sequencing data of patients with psoriasis were obtained, in which differentially expressed genes were assessed by principal component analysis. A diagnostic model was developed using random forest algorithm and validated by receiver operating characteristic (ROC) curves. Subsequently, we performed consensus clustering to calculate angiogenesis-associated molecular subtypes of psoriasis. Additionally, a correlation analysis was conducted between ARGs and immune cell infiltration. Finally, validation of potential ARG genes was performed by quantitative real-time PCR (qRT-PCR). We identified 29 differentially expressed ARGs, including 13 increased and 16 decreased. Ten ARGs, CXCL8, ANG, EGF, HTATIP2, ANGPTL4, TNFSF12, RHOB, PML, FOXO4, and EMCN were subsequently sifted by the diagnostic model based on a random forest algorithm. Analysis of the ROC curve (area under the curve [AUC] = 1.0) indicated high diagnostic performance in internal validation. The correlation analysis suggested that CXCL8 has a high positive correlation with neutrophil (R =0.8, P < 0.0001) and interleukins pathway (R = 0.79, P < 0.0001). Furthermore, two ARG-mediated subtypes were obtained, indicating potential heterogeneity. Finally, the qRT-PCR demonstrated that the mRNA expression levels of CXCL8 and ANGPTL4 were elevated in psoriasis patients, with a reduced expression of EMCN observed. The current paper indicated potential ARG-related biomarkers of psoriasis, including CXCL8, ANGPTL4, and EMCN, with two molecular subtypes.

Rare MED12L Variants Are Associated with Susceptibility to Guttate Psoriasis in the Han Chinese Population

Introduction: According to the common disease/rare variant hypothesis, it is important to study the role of rare variants in complex diseases. The association of rare variants with psoriasis has been demonstrated, but the association between rare variants and specific clinical subtypes of psoriasis has not been investigated. Methods: Gene-based and gene-level meta-analyses were performed on data extracted from our previous study data sets (2,483 patients with guttate psoriasis and 8,292 patients with non-guttate psoriasis) for genotyping. Then, haplotype analysis was performed for rare loss-of-function variants located in MED12L, and protein function prediction was performed for MED12L. Gene-based analysis at each stage had a moderate significance threshold (p < 0.05). A χ2 test was then conducted on the three potential genes, and the merged gene-based analysis was used to confirm the results. We also conducted association analysis and meta-analysis for functional variants located on the identified gene. Results: Through these gene-level analyses, we determined that MED12L is a guttate psoriasis susceptibility gene (p = 9.99 × 10−5), and the single-nucleotide polymorphism with the strongest association was rs199780529 (p_combine = 1 × 10−3, p_meta = 2 × 10−3). Conclusions: In our study, a guttate psoriasis-specific subtype-associated susceptibility gene was confirmed in a Chinese Han population. These findings contribute to a better genetic understanding of different subtypes of psoriasis.

A retrospective analysis of comorbidities in patients with psoriasis at a single centre.

Psoriasis is a chronic inflammatory disease occurring worldwide. It is currently considered a multi-system disease, which is associated with several comorbidities. To deeply understand the clinical characteristics of psoriasis comorbidities and explore the relationship between psoriasis comorbidities, different subtypes and related influencing factors. This retrospective study analysed data from the electronic inpatient medical record system of dermatology and non-dermatology departments at a tertiary hospital in China. We collected relevant demographic data and clinical features of all patients diagnosed with psoriasis from January 2013 to September 2023. This study ultimately included a total of 1097 patients with psoriasis. Psoriasis vulgaris was the most common among the subtypes of psoriasis, with 957 (87.2%) cases. The sample consisted of 65.6% of males and 34.4% of females, with an average age of 53.5 ±15.2 years. Common comorbidities of psoriasis included hypertension (38.2%), hyperlipidaemia (29.4%), type 2 diabetes mellitus (24.6%), fatty liver disease (21.4%), coronary heart disease (21.0%), tumours (15.5%), gastroduodenal disease (14.4%), osteoarthropathy (11.8%), and cerebrovascular disease (10.8%). The incidence of hypertension (p = 0.015), hyperuricemia (p < 0.001), osteoarthropathy (p < 0.001), and autoimmune disease (p = 0.003) among different subtypes of psoriasis showed statistically significant differences. In addition, gender, smoking and alcohol consumption all have significant impacts on the distribution of comorbidities. The distribution of psoriasis comorbidities and complications varies among different subtypes of psoriasis. Lifestyles such as smoking and alcohol abuse, as well as gender, are also associated with the occurrence of psoriasis comorbidities.

Prevalence, outcomes and associated factors of SARS-CoV-2 infection in psoriasis patients of Southwest China: a cross-sectional survey

In this study we aimed to investigate the prevalence of SARS-CoV-2 infection in psoriasis patients, and outcomes of SARS-CoV-2 infection and associated risk factors. A cross-sectional survey was conducted from February 2023 to March 2023. Information was obtained with online questionnaire about psoriasis patients on demographic characteristics, clinical characteristics, SARS-CoV-2 infection and outcomes, vaccination, and routine protection against COVID-19. Logistic regression analysis was used to explore risk factors with SARS-CoV-2 infection and exacerbation of psoriasis. A total of 613 participants were recruited. 516 (84.2%) were infected, and associated factors were sex, working status, routine protection against COVID-19, COVID-19 vaccination, impaired nail, infection exacerbate psoriasis, and severity of psoriasis. Among the patients infected with SARS-CoV-2, 30 (5.8%) required hospitalization, 122 (23.6%) had psoriasis exacerbation due to SARS-CoV-2 infection, and associated factors were subtype of psoriasis, discontinuation of psoriasis treatment during SARS-CoV-2 infection, response following COVID-19 vaccination, and severity of psoriasis. Booster dose vaccination contributed a low probability of COVID-19 sequelae. COVID-19 vaccine’s effectiveness was unsatisfactory, while booster dose vaccination reduced the occurrence of COVID-19 sequelae in psoriasis patients of Southwest China. Patients treated with psoriasis shown to be safe, without a higher incidence of SARS-CoV-2 infection or COVID-19hospitalization compared to untreated patients. Stopping treatment during SARS-CoV-2 infection led to psoriasis exacerbation, so psoriasis treatment could be continued except severe adverse reaction.

Construction and validation of m6A-related diagnostic model for psoriasis.

Psoriasis is a chronic immune-mediated inflammatory disease. N6-methyladenosine (m6A) is involved in numerous biological processes in both normal and diseased states. Herein, we aimed to explore the potential role of m6A regulators in the diagnosis of psoriasis and predict molecular mechanisms by which m6A regulators impact psoriasis. GSE30999 (170 human skin tissue samples) and GSE13355 (180 human skin tissue samples) were downloaded as the training analysis dataset and validation dataset respectively. M6A-related genes were obtained from the literature and their expression levels in GSE30999 samples were measured to identify M6A-related DEGs between psoriasis lesions (LS) and non-lesional lesions (NL). We identified m6A-related DEGs using differential expression analysis and assessed their interactions through correlation analysis and network construction. A logistic regression analysis followed by LASSO optimization was employed to select m6A-related DEGs for the construction of a diagnostic model. The performance of the model was validated using support vector machine (SVM) methodology with sigmoid kernel function and extensive cross-validation. Additionally, the correlation between m6A-related DEGs and immune cell infiltration was analyzed, as well as the association of these DEGs with psoriasis subtypes. Functional analysis of the m6A-related DEGs included the construction of regulatory networks involving miRNAs, transcription factors (TFs), and small-molecule drugs. The m6A modification patterns were also explored by examining the gene expression differences between psoriasis subtypes and their enriched biological pathways. Finally, the expression of significant m6A regulators involved in the diagnostic model was examined by RT-qPCR. In this study, ten optimal m6A-related DEGs were identified, including FTO, IGF2BP2, METTL3, YTHDC1, ZC3H13, HNRNPC, IGF2BP3, LRPPRC, YTHDC2, and HNRNPA2B1. A diagnostic model based on these m6A-related DEGs was constructed, demonstrating high diagnostic accuracy with an area under the curve (AUC) in GSE30999 and GSE13355 of 0.974 and 0.730, respectively. Meanwhile, the expression level of m6A regulators verified by RT-qPCR was consistent with the results in GSE30999. The infiltration of activated mast cells and NK cells was significantly associated with all ten m6A-related DEGs in psoriasis. Among them, YTHDC1, HNRNPC, and FTO were targeted by most miRNAs and were regulated by nine related TFs. Therefore, patients may benefit from dorsomorphin and cyclosporine therapy. Between the two subgroups, 1,592 DEGs were identified, including LRPPRC and METTL3. These DEGs were predicted to be involved in neutrophil activation, cytokine-cytokine receptor interactions, and chemokine signaling pathways. A diagnostic model based on ten m6A-related DEGs in patients with psoriasis was constructed, which may provide early diagnostic biomarkers and therapeutic targets for psoriasis.

Comparison of metabolic and neurological comorbidities in Asian patients with psoriasis and atopic dermatitis

Although various comorbidities have been noted to be associated with atopic dermatitis (AD) and psoriasis, few studies have compared comorbidities between the two diseases, and little is known about whether these comorbidities vary by the subtypes of psoriasis. In this study of 1:1 age- and sex-matched pair analysis between patients diagnosed with either psoriasis or AD at Asan Medical Center between 1991 and 2020, comorbidities, as determined by the International Classification of Diseases-10 codes, and likelihood ratios of metabolic and neurologic comorbidities in psoriasis compared with AD were studied using a logistic regression model. Among a total of 14,128 patients, the psoriasis group had higher odds of obesity (odds ratio [95% confidence interval]: 1.49 [1.34–1.66]), hypertension (1.14 [1.03–1.26]), diabetes mellitus (1.46 [1.29–1.66]), chronic kidney disease (1.59 [1.22–2.08]), and Parkinson's disease (2.1 [1.15–3.83]) than the AD group. Subgroup analysis revealed that patients with plaque psoriasis had higher odds of obesity (1.18 [1.05–1.33]), hypertension (1.18 [1.06–1.32]), diabetes mellitus (1.53 [1.34–1.75]), chronic kidney disease (1.66 [1.26–2.17]), and Parkinson’s disease (2.12 [1.16–3.88]) compared with AD. Meanwhile, guttate psoriasis was associated with higher odds of dementia (3.63 [1.06–12.40]) and patients with generalized pustular psoriasis showed higher odds of diabetes mellitus (5.42 [1.56–18.83]) compared with AD. In conclusion, Asian patients with all types of psoriasis should be closely monitored for the development of metabolic and neurologic diseases, especially men and those aged ≥ 40 years.

Rapid response of nail psoriasis to secukinumab in patients with moderate to severe psoriasis after 12 weeks of treatment with a total of 24 weeks of follow-up.

Nail psoriasis, a subtype of psoriasis, can cause significant pain, disability, and reduced quality of life. Despite the established efficacy of anti-IL17 secukinumab in improving skin psoriasis, there is a lack of clinical trials focusing on nail psoriasis as primary endpoint. This study aims to investigate the efficacy of secukinumab in treating nail psoriasis in patients with moderate to severe psoriasis. We prospectively recruited patients newly diagnosed with moderate to severe psoriasis in single centre from January 2021 to January 2022 who were treated with secukinumab. A total of 16 patients consisting of 9 males and 7 females were included. Their mean age was 38.88 ± 10.29 years. They had an average initial Nail Psoriasis Severity Index (NAPSI) score of 45.06 ± 20.39 and an average NAPSI score at 12 weeks of 8.94 ± 13.50, showing a significant (p < 0.05) decrease of NAPSI score after 12 weeks of secukinumab treatment. After 24 weeks of treatment, NAPSI score was decreased to 5.12 ± 8.52. Secukinumab rapidly improved nail psoriasis after 12 weeks of treatment, with further enhancement at 24 weeks, suggesting its potential as a potent therapeutic option for nail psoriasis.

Causal associations between both psoriasis and psoriatic arthritis and multiple autoimmune diseases: a bidirectional two-sample Mendelian randomization study.

Numerous observational studies have identified associations between both psoriasis (PsO) and psoriatic arthritis (PsA), and autoimmune diseases (AIDs); however, the causality of these associations remains undetermined. We conducted a bidirectional two-sample Mendelian Randomization study to identify causal associations and directions between both PsO and PsA and AIDs, such as systemic lupus erythematosus (SLE), Crohn's disease (CD), ulcerative colitis (UC), multiple sclerosis (MS), uveitis, bullous pemphigoid (BP), Hashimoto's thyroiditis (HT), rheumatoid arthritis (RA), vitiligo, and ankylosing spondylitis (AS). The causal inferences were drawn by integrating results from four regression models: Inverse Variance Weighting (IVW), MR-Egger, Weighted Median, and Maximum Likelihood. Furthermore, we performed sensitivity analyses to confirm the reliability of our findings. The results showed that CD [IVW odds ratio (ORIVW), 1.11; 95% confidence interval (CI), 1.06-1.17; P = 8.40E-06], vitiligo (ORIVW, 1.16; 95% CI, 1.05-1.28; P = 2.45E-03) were risk factors for PsO, while BP may reduce the incidence of PsO (ORIVW, 0.91; 95% CI, 0.87-0.96; P = 1.26E-04). CD (ORIVW, 1.07; 95% CI, 1.02-1.12; P = 0.01), HT (ORIVW, 1.23; 95% CI, 1.08-1.40; P = 1.43E-03), RA (ORIVW, 1.11; 95% CI, 1.02-1.21, P = 2.05E-02), AS (ORIVW, 2.18; 95% CI, 1.46-3.27; P = 1.55E-04), SLE (ORIVW, 1.04; 95% CI, 1.01-1.08; P = 1.07E-02) and vitiligo (ORIVW, 1.27; 95% CI, 1.14-1.42; P = 2.67E-05) were risk factors for PsA. Sensitivity analyses had validated the reliability of the results. Our study provides evidence for potential causal relationships between certain AIDs and both PsO and PsA. Specifically, CD and vitiligo may increase the risk of developing PsO, while CD, HT, SLE, RA, AS, and vitiligo may elevate the risk for PsA. Additionally, it is crucial to closely monitor the condition of PsO patients with specific AIDs, as they have a higher likelihood of developing PsA than those without AIDs. Moving forward, greater attention should be paid to PsA and further exploration of other PsO subtypes is warranted.

Black and male children have an increased risk of palmoplantar psoriasis compared to White children.

A retrospective chart review of 332 pediatric psoriasis patients seen at a single academic institution from 2012 to 2022 was conducted to examine the risk factors associated with palmoplantar psoriasis (PP), a painful and treatment-resistant subtype of plaque psoriasis affecting hands and feet. Black patients have a 6.386-fold increase in the odds of having PP compared to White patients and males have a 2.241-fold increase in the odds of having PP. Black and Hispanic/Latino patients displayed a higher prevalence of nail and palm/sole involvement (p < .0001), whereas White patients exhibited more scalp involvement (p = .04). This study reveals the importance of considering the diagnosis of PP in Black male patients based on its demographic prevalence, which may in turn impact clinical care for these patients.

The update of treatment strategies in pediatrics with generalized pustular psoriasis in China.

Generalized pustular psoriasis (GPP) is a severe subtype of psoriasis, commonly combined with systemic inflammation. Gene mutations have been found to be associated with GPP and vary by ethnicity. Systemic treatments are usually required for the severity and potential complications of GPP. However, there is no common consensus in China, especially among pediatric patients, whose data are scarce. Acitretin, methotrexate, and cyclosporine are widely used in pediatrics with GPP, while the adverse effects should be highlighted. The emergence of different biological agents brings us into a new era. This article discusses the genetic background of Chinese patients and demonstrates the evidence of treatment in pediatrics with GPP.

A Systematic Review of Follicular Psoriasis: A Unique but Under-Recognized Entity.

Follicular psoriasis (FP) is a rare and under-recognized subtype of psoriasis that affects hair follicles and can be frequently misdiagnosed due to its unique presentation. We aimed to analyze the frequently reported clinical, histological, and dermatoscopic features of FP, as well as their treatment options. We conducted a systematic review of the PubMed/MEDLINE database using the search terms "follicular" and "psoriasis." Fourteen studies were included yielding information on 44 patients (27 adults [61.4%] and 17 children [38.6%]). Adult FP showed a female predominance (M:F = 1:2.7), frequent involvement of lower extremities (81.5%), association with metabolic syndrome including diabetes mellitus (22.2%), and a predilection for skin of color (SOC:White = 8:1). On the contrary, juvenile FP revealed male predominance (M:F = 1:0.6), frequent involvement of the trunk (41.2%), and exclusive involvement in skin of color (SOC:White = 11:0). In addition to its unique presentation, FP tends to be misdiagnosed due to its low incidence of concomitant psoriasis (31.8%), and rare personal (18.2%) or family history (6.8%) of psoriasis. Reported histopathological features include keratotic plugging, follicular parakeratosis with or without neutrophils, psoriasiform acanthosis, hypogranulosis, and neutrophilic infiltration of follicular epithelium. Dermatoscopic findings include folliculocentric lesions with normal appearing terminal hairs, perifollicular white scale, and various vascular structures. Once correctly diagnosed, patients with FP showed improvement or resolution of symptoms with various combinations of topical and systemic therapies. Understanding the demographic features and clinical presentations of FP can help address under-recognition of this clinical variant of psoriasis.

Acceptance of a digital therapy recommender system for psoriasis

BackgroundAbout 2% of the German population are affected by psoriasis. A growing number of cost-intensive systemic treatments are available. Surveys have shown high proportions of patients with moderate to severe psoriasis are not adequately treated despite a high disease burden. Digital therapy recommendation systems (TRS) may help implement guideline-based treatment. However, little is known about the acceptance of such clinical decision support systems (CDSSs). Therefore, the aim of the study was to access the acceptance of a prototypical TRS demonstrator.MethodsThree scenarios (potential test patients with psoriasis but different sociodemographic and clinical characteristics, previous treatments, desire to have children, and multiple comorbidities) were designed in the demonstrator. The TRS demonstrator and test patients were presented to a random sample of 76 dermatologists attending a national dermatology conference in a cross-sectional face-to-face survey with case vignettes. The dermatologist were asked to rate the demonstrator by system usability scale (SUS), whether they would use it for certain patients populations and barriers of usage. Reasons for potential usage of the TRS demonstrator were tested via a Poisson regression with robust standard errors.ResultsAcceptance of the TRS was highest for patients eligible for systemic therapy (82%). 50% of participants accepted the system for patients with additional comorbidities and 43% for patients with special subtypes of psoriasis. Dermatologists in the outpatient sector or with many patients per week were less willing to use the TRS for patients with special psoriasis-subtypes. Dermatologists rated the demonstrator as acceptable with an mean SUS of 76.8. Participants whose SUS was 10 points above average were 27% more likely to use TRS for special psoriasis-subtypes. The main barrier in using the TRS was time demand (47.4%). Participants who perceived time as an obstacle were 22.3% less willing to use TRS with systemic therapy patients. 27.6% of physicians stated that they did not understand exactly how the recommendation was generated by the TRS, with no effect on the preparedness to use the system.ConclusionThe considerably high acceptance and the preparedness to use the psoriasis CDSS suggests that a TRS appears to be implementable in routine healthcare and may improve clinical care. Main barrier is the additional time demand posed on dermatologists in a busy clinical setting. Therefore, it will be a major challenge to identify a limited set of variables that still allows a valid recommendation with precise prediction of the patient-individual benefits and harms.

Comprehensive Analysis to Identify Rh Family C Glycoprotein (RHCG) as the Causative Gene for Psoriasis and Search for Alternative Treatment Modalities.

Psoriasis is a complex autoimmune disease. Frequent interactions between epidermal and immune cells are likely to be responsible for the strong heterogeneity of psoriasis. Therefore, our work aims to build on current knowledge and further search for new molecular mechanisms related to psoriasis pathogenesis in order to develop new targeted drugs. Data from psoriasis samples were obtained from the Gene Expression Omnibus (GEO) database, and batch effects were corrected using the "Combat" algorithm in the "SVA" package. Functional annotation of differential genes in psoriasis was performed by Gene set enrichment analysis (GSEA). Core functional modules were identified using the Multiscale Embedded Gene Co-Expression Network Analysis (MEGENA) algorithm for selection from the differential gene interaction network. The expression and potential function of Rh Family C Glycoprotein (RHCG) was predicted in single cell data by the "Seurat" package and validated in psoriasis samples by multiplex immunofluorescence. In addition, the regulatory function of HOP Homeobox (HOPX) on RHCG in keratinocytes was confirmed using RNA interference. Using immune infiltration analysis, RHCG and DC cells were analyzed for their association. Finally, the molecular mechanisms of treatment of psoriasis using Tripterygii Radix (TR) and Cinnamomi Ramulus (CR) were explored through network pharmacology and experimental validation. Immune response (represented by C1_2) and collagen matrix formation (represented by C1_3) were identified as two important pathogenic factors in psoriasis and helped to define new biological subtypes of psoriasis. One important psoriasis hub gene, RHCG, was obtained and found to be closely associated with keratinocyte differentiation as well as DC cell maturation. And RHCG was regulated by HOPX in keratinocytes. In addition, the mechanism of action of CR and TR in the treatment of psoriasis was tentatively confirmed to be related to TRPV3, NFKB2, and YAP1. Our study identifies a new causal disease gene (RHCG) and offers potential alternatives for the treatment of psoriasis.

Effectiveness of biologic therapies in children with palmoplantar plaque psoriasis: An analysis of real-life data from the BiPe cohorts.

Palmoplantar plaque psoriasis is a frequent clinical subtype of childhood psoriasis. This study evaluated the effectiveness of biologic therapies in children with palmoplantar plaque psoriasis using data from the two Biological treatments for Pediatric Psoriasis (BiPe) cohorts. Data for all 170 patients included in the BiPe cohorts were analyzed. Data on the effectiveness (PGA, PASI between baseline and 3 months of treatment) of biologic therapies were then compared between children with palmoplantar plaque psoriasis (n = 20) and those with generalized plaque psoriasis (n = 136). Clinical and demographic data were also analyzed. Children in the palmoplantar group were more likely to be male (p = .04), with an earlier age of psoriasis onset (p < .001), and more frequent nail involvement (p < .001). After 3 months of biologic treatment, mean PGA scores were higher in the palmoplantar group than in the generalized plaque psoriasis group (p = .004). In the palmoplantar group, continuation rates were higher for adalimumab than for etanercept or ustekinumab (p = .01). Primary inefficacy was a more frequent reason for stopping biologic therapies in the palmoplantar group (p = .01), and disease remission was less frequent (p = .05). Combined systemic and biologic therapies were more frequently used in palmoplantar plaque psoriasis (p < .001). This study demonstrated the treatment-resistant nature of palmoplantar plaque psoriasis and indicated that adalimumab could be the most effective biologic treatment. Larger studies are needed to allow therapeutic algorithms for palmoplantar plaque psoriasis to be proposed in pediatric psoriasis management guidelines.

Group A Streptococcus induces CD1a-autoreactive T cells and promotes psoriatic inflammation.

Group A Streptococcus (GAS) infection is associated with multiple clinical sequelae, including different subtypes of psoriasis. Such post-streptococcal disorders have been long known but are largely unexplained. CD1a is expressed at constitutively high levels by Langerhans cells and presents lipid antigens to T cells, but the potential relevance to GAS infection has not been studied. Here, we investigated whether GAS-responsive CD1a-restricted T cells contribute to the pathogenesis of psoriasis. Healthy individuals had high frequencies of circulating and cutaneous GAS-responsive CD4+ and CD8+ T cells with rapid effector functions, including the production of interleukin-22 (IL-22). Human skin and blood single-cell CITE-seq analyses of IL-22-producing T cells showed a type 17 signature with proliferative potential, whereas IFN-γ-producing T cells displayed cytotoxic T lymphocyte characteristics. Furthermore, individuals with psoriasis had significantly higher frequencies of circulating GAS-reactive T cells, enriched for markers of activation, cytolytic potential, and tissue association. In addition to responding to GAS, subsets of expanded GAS-reactive T cell clones/lines were found to be autoreactive, which included the recognition of the self-lipid antigen lysophosphatidylcholine. CD8+ T cell clones/lines produced cytolytic mediators and lysed infected CD1a-expressing cells. Furthermore, we established cutaneous models of GAS infection in a humanized CD1a transgenic mouse model and identified enhanced and prolonged local and systemic inflammation, with resolution through a psoriasis-like phenotype. Together, these findings link GAS infection to the CD1a pathway and show that GAS infection promotes the proliferation and activation of CD1a-autoreactive T cells, with relevance to post-streptococcal disease, including the pathogenesis and treatment of psoriasis.