Psoriasis is a chronic autoimmune disease that significantly impairs patients' quality of life. With the growing availability of biologic drugs - each varying in efficacy, safety, dosing, and cost - treatment decisions have become increasingly complex. A study conducted from March to July 2024 surveyed 302 Vietnamese patients with moderate to severe psoriasis to assess preferences for biologic therapies. Using a discrete choice experiment (DCE), participants evaluated 6 treatment attributes: short-term efficacy, long-term efficacy, sustained efficacy after drug withdrawal, frequency of administration, copayment, and risk of serious infection. Preference data were analysed using conditional logit models. Analysis revealed that treatment cost (relative importance [RI]: 31.4%) and long-term efficacy (RI: 25.3%) were the most critical factors influencing patient decisions, while sustained efficacy after withdrawal and early onset of efficacy were less impactful. Long-term efficacy and cost consistently ranked highest across all patient subgroups, with variations depending on demographic and clinical characteristics. These findings provide practical guidance for clinicians to incorporate patient preferences into the selection of biologic therapies, with particular emphasis on treatment cost and long-term efficacy. The significant influence of treatment cost also highlights the need for healthcare policymakers in Vietnam to enhance reimbursement policies and financial support programmes, improving access and equity in psoriasis care.

Several observational studies have reported epidemiologic associations between psoriasis and risk of some cancers, but systematic evidence is lacking. Our aim was to comprehensively estimate the association between psoriasis and the risk of 33 common cancers using systematical Mendelian randomization based on genetic data.

Forty-nine independent single-nucleotide polymorphisms (SNPs) significantly associated with psoriasis were extracted as instrumental variables from a large-scale meta-analysis study of genome-wide association study (GWAS) for psoriasis. Outcome GWAS data were obtained from the FinnGen consortium (n = 500,348), UK Biobank (n = 420,531), and other large-scale cancer datasets. The inverse-variance weighted (IVW) was used as the primary method to infer the association between psoriasis and risk of cancer, and finally the results from multiple databases were pooled by meta-analysis.

In the UK Biobank, genetically predicted psoriasis had a suggestive association with colon (OR = 1.055, 95%CI: 1.001-1.113, P = 0.046) and uterine corpus cancer (OR = 0.922, 95%CI: 0.852-0.997, P = 0.042). In the FinnGen consortium, psoriasis had a suggestive association with vulvar cancer (OR = 1.182, 95%CI: 1.023-1.366, P = 0.024), uterine corpus cancer (OR = 0.937, 95%CI: 0.883-0.993, P = 0.028), and prostate cancer (OR = 0.973, 95%CI: 0.948-0.999, P = 0.045). In an additional large-scale cancer dataset, psoriasis also showed a suggestive association with prostate cancer (OR = 0.968, 95%CI:0.942-0.995, P = 0.020). The meta-analysis confirmed the suggestive association of psoriasis with uterine corpus (OR = 0.931, 95% CI: 0.889-0.976, P = 0.003) and prostate cancer (OR = 0.976, 95% CI: 0.955-0.997, P = 0.023). Whereas the effect of psoriasis on colon and vulvar cancer was not in the same direction across different populations. Furthermore, no association between genetically predicted psoriasis and other cancers were observed.

This comprehensive MR study suggests that psoriasis may be a potential protective factor for uterine corpus cancer in women and prostate cancer in men.

Bimekizumab, an interleukin (IL)-17A/IL-17F inhibitor, is effective for moderate-to-severe psoriasis. However, long-term maintenance of early treatment outcomes is not examined in real-world settings, with no analyses stratified by dosing intervals (every 4 weeks [Q4W] vs. 8 weeks [Q8W]) or histories of biologics (bio-naïve vs. bio-switched). We investigated whether the outcomes achieved at week 16 of bimekizumab treatment may be maintained until week 52, stratified by dosing intervals or histories of biologics. This prospective study included 63 Japanese patients (≥15 years) with moderate-to-severe psoriasis. All the patients received bimekizumab 320 mg Q4W until week 16, thereafter Q4W or Q8W. We evaluated the maintenance rates until week 52 for Psoriasis Area and Severity Index (PASI) 75, PASI 90, PASI 100, absolute PASI ≤2, absolute PASI ≤1, Static Physician's Global Assessment (sPGA) 0/1, or Dermatology Life Quality Index (DLQI) 0/1 achieved at week 16, stratified by dosing intervals or histories of biologics. In total patients, the maintenance rates for PASI 75, absolute PASI ≤2 or ≤1, or sPGA 0/1 were mostly 100% until week 52 while those for DLQI 0/1 decreased to around 80%, irrespective of dosing intervals or biologic histories. The maintenance rates for PASI 90 and 100 were mostly 100% in the Q4W group and bio-naïve patients in the Q8W group while both decreased to 71.4% at week 52 in bio-switched patients in the Q8W group. This study showed that the improvement of skin lesions at week 16 of bimekizumab treatment can be almost completely maintained until week 52.

Psoriasis significantly impacts patients' mental health and social relationships, often leading to feelings of stigmatization and shame due to the visibility of skin lesions. This study aimed to identify factors influencing the quality of life in patients with psoriasis.

A cross-sectional study was conducted from November 2018 to December 2020, involving 100 patients treated for psoriasis. The research utilized the WHO Quality of Life Questionnaire (WHOQoL-Bref), the Psoriasis Area and Severity Index (PASI), the Acceptance of Illness Scale (AIS), the Hospital Anxiety and Depression Scale (HADS), and the Mini Nutritional Assessment (MNA). The analysis included demographic, clinical, and psychological variables to evaluate their impact on quality of life.

The multivariate linear regression model revealed that significant independent predictors of quality of life included age (p=0.001), duration of disease (p=0.004), and nutritional status (p=0.002). In the physical domain, factors such as phototherapy (r=2.46) and anxiety levels assessed by the HADS anxiety subscale (r=-0.23) were particularly relevant. In the psychological domain, the presence of psoriatic arthritis (r=1.978), hand and foot psoriasis (r=2.34), and scores on the HADS anxiety (r=-0.212) and depression subscales (r=-0.226) were significant. Male gender (r=1.632) and depressive symptoms (r=-0.352) impacted the social domain. In the environmental domain, predictors included erythrodermic psoriasis (r=1.98), hand and foot psoriasis (r=2.312), phototherapy (r=1.877), PASI score (r=-0.04), and depression as measured by HADS (r=-0.228).

The primary predictors of quality of life in patients with psoriasis are the type of psoriasis, the presence of anxiety and depressive disorders, and treatment with phototherapy. However, the study's single-center design and relatively small sample size may limit the generalizability of the findings. Further multi-center studies are needed to confirm these results and broaden their applicability.

Psoriasis is a chronic, relapsing inflammatory skin disorder that causes a detrimental physical and psychological impact on people living with the disease. However, little is known about its current prevalence, clinical variants, and quality of life among patients in Uganda.

The purpose of this study was to determine the prevalence of psoriasis, clinical variants, and quality of life (QoL) among patients attending Skin Clinic, Mbarara Regional Referral Hospital (MRRH), in western Uganda.

A cross-sectional study design and consecutive sampling were used. It was conducted between January and March 2023 at the skin clinic, MRRH, with a sample size of 384. The patients were thoroughly examined to assess clinical variants, and Quality of Life was evaluated using the Dermatology Life Quality Index (DLQI). Data obtained was entered using Excel version 20 and analyzed using STATA version 12.0 and GraphPad Prism 9.00. Descriptive statistics and comparison analysis (students t-test and ANOVA) were done.

The overall prevalence of psoriasis was 3.91%. Majority of cases (86.67%) had chronic plaque psoriasis, 60% had a severe disease, and 60% were between 4 and 40 years. Most affected sites were arms (60%) and back (60%) and shins (53.33%), and the least affected were nails and dorsal feet (6.67%). Psoriasis moderately reduces QoL, with an overall mean DLQI score of 8.95 ± 1.35. There was no significant difference between QoL and age or gender.

Prevalence of psoriasis at MRRH in western Uganda is 3.91%. Chronic plaque psoriasis was the most common variant (86.67%), and the disease moderately affects the quality of life.

Efferocytosis of macrophages infiltrated in psoriatic lesions is mostly impaired, thus promoting the progression of psoriasis. Herein, we reveal that there exists a feedback loop between activated platelets and efferocytosis-impaired macrophages in psoriatic. Or rather, efferocytosis-impaired macrophages stimulate platelet activation, which in turn down-regulates the expression of the phagocytic receptor Mer on macrophages and polarizes macrophages to the M1-phenotype of weaker efferocytosis ability. Therefore, we construct a combined nanoplatform for more precise targeting to efferocytosis-impaired macrophages and activated platelets. The macrophage-targeting part of the nanoplatform efficiently orientates to efferocytosis-impaired macrophages through macrophage membrane encapsulation and targeting peptide modification. This increases the expression of Mer, simultaneously enhances the acidification and maturation of efferosomes, ultimately restores efferocytosis of macrophages, and promotes the phagocytosis and clearance of apoptotic cells. On the other hand, the activated platelet-targeting nanoparticles inhibit the activation of platelets, thus blocking the feedback loop and eventually preventing the down-regulation of Mer expression on macrophages. Furthermore, the combined nanoplatform suppresses the infiltration of macrophages and platelets in psoriatic lesions, reduces the release of pro-inflammatory factors such as IL-17A, and consequently improves the therapeutic effect of psoriasis and prevention of its recurrence in vivo. Collectively, this two-pronged strategy with multifunctionality in repairing efferocytosis, inhibiting platelet activation, and blocking the feedback loop may provide options available for the treatment of psoriasis.

Plaque psoriasis is a common, chronic, papulosquamous skin disorder. TNF, IL-17 and IL-23 have been identified as key cytokines in the pathogenesis of psoriasis. Certain human leukocyte antigen (HLA) variants, such as HLA-Cw6 and HLA-B27, were proposed to affect the clinical course of the disease and the response to standard and biological treatment. In individuals positive for HLA-B27, psoriatic arthritis tends to progress more rapidly, with a higher prevalence of dactylitis and nail changes, suggesting HLA-B27 being a genetic biomarker for early-onset psoriatic arthritis. HLA-Cw6 is associated with the early onset of cutaneous manifestations in psoriasis. In these cases, cutaneous lesions are commonly localised on the chest and limbs, with less pronounced scalp and nail involvement. Psoriatic arthritis tends to develop later in HLA-Cw6-positive patients. The presence of HLA-Cw6 is associated with a more favourable therapeutic response to methotrexate and p40IL-12/23 inhibitors than to TNF inhibitors. Therefore, HLA-Cw6 testing may be a valuable tool for identifying patients who are likely to benefit from treatment with specific monoclonal antibodies, especially p40IL-12/23 inhibitors.

Musculoskeletal pain associated to psoriasis without the presence of psoriatic arthritis is a poor explored issue in pediatric population. The aim of this study was to compare the health-related quality of life (HRQoL) and fatigue scores of pediatric patients with psoriasis and healthy peers and estimate the impact of musculoskeletal pain.

The pediatric Gait Arms Legs and Spine (pGALS) questions were used to screen for musculoskeletal pain. General HRQoL was measured using the Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL 4.0) and fatigue was assessed using the PedsQL-Multidimensional Fatigue Scale (PedsQL-MFS).

Fifty psoriatic patients (12.1years old; IQR 9-15) and 50 controls (12.3 years old; IQR 8.8-15.9) were evaluated. Patients with psoriasis had long disease duration of 6.9 years (IQR 3.7-9.5) and predominantly low disease activity (PASI 3.2, IQR 0.8-6; BSA 3.0, IQR 1-8), mainly treated with topical therapy. The PedsQL 4.0 total score of psoriatic patients with musculoskeletal pain was poorer than controls with pain. Fatigue by PedsQL-MFS was also worse in patients with psoriasis and pain. The risk of impaired HRQoL was 7.7 times higher in the presence of musculoskeletal pain (OR = 7.71, 95%CI 1.66-35.78); other variables such as age, sex and severity of psoriasis did not increase the risk of HRQoL impairment.

Musculoskeletal pain and fatigue may provide clues for systemic impairment in pediatric psoriatic disease and calls for effective systemic treatment to reduce disease burden and accumulated damage.

Bimekizumab and brodalumab are characterized by a different mechanism of action if compared to the other anti-interleukin (IL)-17s which target IL-17A. Indeed, brodalumab acts on IL-17RA whereas bimekizumab acts on IL-17A, IL-17F, and IL-17AF cytokines. Currently, despite real-life data on the efficacy and safety of bimekizumab and brodalumab have been reported, data comparing these two drugs are absent. However, these data are mandatory to evaluate whether a different target of the same IL can be correlated with a different profile in terms of effectiveness and safety. Moreover, it should be underlined that bimekizumab and brodalumab stood out as the psoriasis treatments with the fastest onset of action, delivering quicker therapeutic responses compared to other drugs acting on IL-17.

A monocentric retrospective study was carried out enrolling patients affected by moderate to severe psoriasis undergoing treatment with brodalumab or bimekizumab. At baseline, clinical demographic details were collected. Clinical improvement [Psoriasis Area Severity Index (PASI), body surface area (BSA)] was collected at weeks 4, 16, and 36. Safety data were analyzed at the same timepoints.

A total of 125 patients were enrolled in the study [bimekizumab: 53 (42.40%); brodalumab: 72 (57.6%)]. Psoriasis severity at baseline was similar between the two cohorts. Both PASI and BSA significantly reduced at each follow-up for both treatment cohorts. The bimekizumab group reached a higher percentage of PASI90/PASI100 response at each timepoint as compared to the brodalumab cohort. In particular, the percentage of PASI100 response was significantly higher in the bimekizumab group as compared to the brodalumab cohort at week 4 (41.5% vs 23.6%, p < 0.05) and at week 16 (67.9% vs 48.6%). Discontinuation for ineffectiveness was higher in the brodalumab cohort (8.3%) as compared to the bimekizumab group (3.8%), without statistical significance. As regards safety, two cases of eczematous reactions (bimekizumab: 2, brodalumab: 0), and five cases of candidiasis (bimekizumab: 4, brodalumab: 1) were collected. Overall, 3 (5.7%) and 1 (1.4%) patients discontinued bimekizumab and brodalumab because of adverse events, respectively.

Our study confirmed the efficacy and safety of both bimekizumab and brodalumab, up to 36 weeks of treatment. Although both drugs showed a significant improvement of the investigated scores from week 4, some differences in terms of PASI90 and PASI100 responses (higher for bimekizumab at each follow-up, with only PASI100 response significantly higher at week 4 and 16) were registered. No statistical significance was found for safety data and treatment failure.

Recently, adalimumab has become an important drug frequently used by dermatologists in the treatment of Hidradenitis suppurativa. While there are many publications by rheumatologists about the risk of hepatitis B and tuberculosis reactivation, the literature on reactivation in the treatment of hidradenitis is not extensive. With this study, we wanted to emphasize that adalimumab is a safe drug despite the risk of hepatitis B and tuberculosis reactivation and the importance of porphylaxis during the treatment of hidradenitis suppurativa.

In this study, data from 462 HS patients followed up at the Dicle University Dermatology Clinic between 1 January 2017 and 30 June 2024 were retrospectively analyzed. Adalimumab use was detected in 56 of the 462 patients. Patients over 18 years of age and used adalimumab for at least 6 months were selected for this study. Two of these patients were not included in the study because they did not meet the criteria for age and duration of adalimumab use.

Of the 12 patients at risk of hepatitis B reactivation during adalimumab treatment, 8 received entecavir, and 4 received tenofovir prophylaxis. No hepatitis B reactivation was observed in any of the 12 patients during adalimumab treatment. Among the 54 patients, 4 were at risk of TB reactivation, and 4 received isoniazid as preophylactic treatment. None of the 4 patients were observed to have TB reactivation.

Adalimumab has become a frequently preferred drug in the treatment of hidradenitis, and it is known that there is a risk of hepatitis b and TBc reactivation, which should be prevented. Despite these risks, we found that adalimumab can be safely used to treat hidradenitis suppurativa, especially with the use of prophylaxis.

Safe and effective treatments for psoriasis are limited. Anisole is an active ingredient in citrus and basil volatile oils; however, its potential for psoriasis treatment remains unexplored. To investigate the effects and mechanism of anisole transdermal administration as a treatment for psoriasis. Imiquimod (IMQ) was used to establish a C57 mouse psoriasis model. The severity of psoriasis lesions in each group was assessed by evaluating the thickness of skin lesions, erythema, and scales. Pathological changes within the epidermis organization were evaluated via hematoxylin and eosin (H&E) staining using light microscopy. Serum inflammatory factor levels were measured by enzyme-linked immunosorbent assays. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) were performed to analyze the mRNA levels of relevant inflammatory factors and the expression of key proteins at the skin lesion sites in psoriatic mice. In model mice, applying anisole hydrogels significantly reduced the serum levels of pro-inflammatory factors interleukin (IL)-17A, (IL)-23, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. H&E staining revealed significantly attenuated stratum spinosum thickening and lymphocyte infiltration in the treatment group. RT-qPCR results further demonstrated that the skin tissues from the treatment group exhibited significantly reduced Il1b, Il17a, Il22, and Tnfa mRNA expression. Western blotting revealed inhibition of the JAK1/STAT3 signaling pathway within anisole-treated psoriatic tissues. Anisole potentially reduces psoriatic-associated inflammation through the JAK1/STAT3 signaling pathway, alleviating IMQ-induced psoriasis.

Growth arrest and DNA damage-inducible 45 (GADD45) proteins are critical stress sensors rapidly induced in response to genotoxic/physiological stress and regulate many cellular functions. Even though the primary function of the proteins is to block the cell cycle, inhibit cell proliferation, promote cell apoptosis, and repair DNA damage to cope with the damage caused by internal and external stress on the body, evidence has shown that GADD45 also has the function to modulate innate and adaptive immunity and plays a broader role in inflammatory and autoimmune diseases. In this review, we focus on the immunomodulatory role of GADD45 in inflammatory and autoimmune diseases. First, we describe the regulatory factors that affect the expression of GADD45. Then, we introduce its immunoregulatory roles on immune cells and the critical signaling pathways mediated by GADD45. Finally, we discuss its immunomodulatory effects in various inflammatory and autoimmune diseases.

Psoriasis may significantly affect the health-related quality of life (HRQoL) of patients. Clinical assessment has been combined with HRQoL scores to evaluate the ways in which cutaneous disease affects patients. Tildrakizumab is a humanized IgG1 monoclonal antibody that targets the p19 subunit of interleukin-23 and is approved for the management of moderate-to-severe plaque psoriasis.

To evaluate the impact of tildrakizumab treatment on the psychological symptoms experienced by patients with moderate-to-severe plaque psoriasis.

A 36-week observational study that enrolled patients with psoriasis who initiated treatment with tildrakizumab 100 mg was carried out. The Dermatology Life Quality Index (DLQI) and Skindex-16 questionnaires were administered at baseline and at weeks 12, 24 and 36. Psoriasis Area Severity Index (PASI), body surface area (BSA) involvement (%) and a visual analogue scale for pruritus (p-VAS) were also assessed at baseline and at each follow-up visit.

Thirty-four patients were enrolled. Baseline mean (SD) PASI score and BSA involvement were 28.4 (5.6) and 38.8 (21.4), respectively. The mean (SD) DLQI, Skindex-16 and p-VAS scores at baseline were 26.4 (3.2), 68 (5.8) and 8.2 (SD not available for p-VAS). Clinical improvement was assessed at weeks 12 [PASI: 12.4 (4.2); BSA involvement: 16.5 (7.3)], 24 [PASI: 4.2 (2.8); BSA involvement: 6.1 (3.1)] and 36 [PASI: 3.6 (3.2); BSA involvement: 4.2 (1.37)]. Clinical improvement was accompanied by an improvement in quality of life at weeks 16 [DLQI: 15.5 (2.9); Skindex-16: 28.2 (4.2); p-VAS: 3.8], 24 [DLQI: 8.2 (1.4); Skindex-16: 16.2 (3.6); p-VAS: 2.6] and 36 [DLQI: 3.1 (2.4); Skindex-16: 9.3 (2.8); p-VAS: 2.8]. Our study also confirmed the safety of tildrakizumab in real-life settings, with no treatment discontinuation due to inefficacy or adverse events.

Our results confirm tildrakizumab as an effective treatment option for improving the HRQoL of patients with psoriasis.

This study investigates the efficacy of monobenazone, a novel topical agent, in treating psoriasis-like lesions in an imiquimod (IMQ)-induced murine model. Female BALB/c mice were allocated to four groups: negative control, IMQ-treated positive control, monobenazone treatment, and clobetasol propionate treatment. The Psoriasis Area and Severity Index (PASI), histopathological analysis, and cytokine quantification (TNF-α and IL-6) were used to assess treatment outcomes. Monobenazone significantly reduced PASI scores and ameliorated histopathological features, including acanthosis and dermal inflammation, compared to the positive control. Furthermore, monobenazone treatment resulted in decreased levels of pro-inflammatory cytokines TNF-α and IL-6. These findings suggest that monobenazone exhibits therapeutic potential in mitigating psoriasis-like symptoms, potentially through modulation of inflammatory responses. While promising, further research is necessary to elucidate its mechanism of action and clinical applicability as a novel psoriasis treatment.

To evaluate the association between sun-protective behaviours and psoriasis in a nationally representative sample of US adults.

Analysis of cross-sectional data.

National Health and Nutrition Examination Survey (NHANES), 2009-2014.

A total of 9735 participants aged 20-59 years with available data on psoriasis, sun-protective behaviours and covariates were included in the analysis.

Information on sun-protective behaviours (staying in the shade, wearing long sleeves and using sunscreen) and psoriasis was obtained from questionnaires in the NHANES database. Logistic regression models and subgroup analyses were employed to investigate the association between sun-protective behaviours and psoriasis.

After adjusting for sociodemographic variables, body mass index (BMI), alcohol drinking status, smoking status, sun sensitivity and time spent outdoors in the multivariable logistic regression model, moderate wearing of long sleeves was negatively associated with psoriasis (OR, 0.55; 95% CI 0.33 to 0.90, p=0.02), while frequent wearing showed no significant relationship. There was no significant association between staying in the shade and psoriasis, regardless of frequency. Subgroup analyses stratified by age, gender, race/ethnicity and smoking status revealed no significant associations in most groups, but moderate wearing of long sleeves was found to be negatively associated with psoriasis among those aged 20-39 years (OR, 0.42; 95% CI 0.18 to 0.98, p=0.04), among non-Hispanic white individuals (OR, 0.52; 95% CI 0.28 to 0.97, p=0.04) and among non-smokers (OR, 0.49; 95% CI 0.25 to 0.95, p=0.04), as it was among women in terms of overall sun protection (OR, 0.58; 95% CI 0.35 to 0.97, p=0.04). However, among non-Hispanic white individuals (staying in the shade: OR, 1.69; 95% CI 1.00 to 2.84, p=0.049) and former/current smokers (overall: OR, 3.28; 95% CI 1.41 to 7.63, p=0.009), frequent sun protection was positively associated with psoriasis.

Moderate sun-protective behaviours among US adults were found to be negatively associated with psoriasis. However, among non-Hispanic white individuals and former/current smokers, frequent sun protection was positively associated with psoriasis. Future studies with rigorous study design could further explore and validate the potential reasons for these associations to better inform evidence-based behavioural recommendations that protect human health.

Primary Sjögren's Syndrome (PSS) and psoriasis are frequently observed to co-occur in clinical settings. However, the causal associations and underlying mechanisms between PSS and psoriasis remain poorly defined. In this study, we conducted bidirectional MR analysis to explore the causal relationship between PSS and psoriasis using four MR methods: inversevariance weighted, MR-Egger regression, weighted median, and weighted mode. Sensitivity analyses were carried out, employing different models and testing methods for comparison to assess the influence of heterogeneity and pleiotropy on our findings and to confirm the robustness of these results. We primarily employed the Inverse Variance Weighting (IVW) method for our analysis. A p-value of less than 0.05 indicates a significant causal relationship, while a p-value greater than 0.05 suggests the absence of such a relationship. The IVW analysis confirmed a causal relationship between psoriasis and primary Sjögren's syndrome (PSS) (OR: 3.149E-10, 95% CI 1.114E-18-0.089, P = 0.028), with the weighted median yielding similar results. Conversely, there was no causal association found between PSS and the risk of developing psoriasis (OR: 1.000, 95% CI 0.999-1.000, P = 0.328). This study reveals a causal relationship between primary Sjögren's syndrome (PSS) and psoriasis, demonstrating that psoriasis increases the risk of developing PSS, while the reverse is not true. This potential causal link offers new insights into the etiology of both PSS and psoriasis.

Psoriasis is a common chronic, recurrent, immune-mediated disease involved in the skin or joints or both. However, deeper insight into the genetic susceptibility of psoriasis is still unclear.

Here we performed the largest multi-ancestry meta-analysis of genome-wide association study including 28,869 psoriasis cases and 443,950 healthy controls.

We identified 74 genome-wide significant loci for psoriasis. Of 74 loci, 32 were novel psoriasis risk loci. Across 74 loci, 801 likely causal genes are indicated and 164 causal genes are prioritized. SNP-based heritability analyses demonstrated that common variants explain 15% of genetic risk for psoriasis. Gene-set analyses and the genetic correlation revealed that psoriasis-related genes have the positive correlations with autoimmune diseases such as ulcerative colitis, inflammatory bowel diseases, and Crohn's disease. Gene-drug interaction analysis suggested that psoriasis-associated genes overlapped with targets of current medications for psoriasis. Finally, we used the multi-ancestry meta-analysis to explore drug repurposing and the potential targets for psoriasis.

We identified 74 genome-wide significant loci for psoriasis. Based on 74 loci, we provided new biological insights to the etiology of psoriasis. Of clinical interest, we gave some hints for 76 potential targets and drug repurposing for psoriasis.

Psoriasis is a chronic inflammatory condition that is polygenic and multisystemic, impacting approximately 2-3% of the global population. The onset of this disease is influenced by an intricate interplay of genetic and environmental factors, predisposing individuals to the psoriasis phenotype. The complex pathogenesis of psoriasis contains certain key aspects found in other autoinflammatory and autoimmune dermatological diseases. Among these, vitiligo, alopecia areata, hidradenitis suppurativa, vitiligo, connective tissue diseases, bullous dermatoses, and atopic dermatitis are conditions that share overlapping immune system dysfunction, making their relationship with psoriasis particularly significant. For our research, we explored various terms including "shared", "concomitant", "coincident", "overlap", "coexist", and "concurrent", in relation to conditions such as "psoriasis", "alopecia areata", "hidradenitis suppurativa", "atopic dermatitis", "vitiligo", "bullous pemphigoid", "pemphigus vulgaris", "lupus erythematosus", "dermatomyositis", and "systemic sclerosis." Additionally, we used specific search queries like "atopic dermatitis overlapping syndrome" and "psoriasis and vitiligo concomitant disease" in the PubMed and Web of Science databases. While distinct in their clinical presentation, the skin diseases related to psoriasis may become associated, complicating diagnosis and treatment. In this narrative review, the complex pathophysiology of psoriasis is described, along with its close relationship to other skin conditions. This review provides an exhaustive description of both immunological and non-immunological pathways contributing to their development. Understanding the intricate interconnection between psoriasis and these conditions is of interest to scientists in developing novel research directions and to clinicians in providing holistic care, as managing one condition may influence the course of others.

Psoriasis is a chronic, immune-mediated skin disease significantly impacting women, with disease severity often modulated by hormonal fluctuations. This review examines the influence of hormonal changes on the course of psoriasis in women, focusing on key life stages-including the menstrual cycle, pregnancy, postpartum, and menopause-and their impact on disease progression and symptomatology. Estrogen, the principal female sex hormone, plays a critical role in immune modulation. Variations in estrogen levels, which occur naturally throughout a woman's life, are associated with fluctuations in psoriasis severity. Low estrogen levels, as seen during menstruation or menopause, are linked to symptom exacerbation, while elevated levels during pregnancy may reduce symptoms in some women. However, responses are variable, with others experiencing no change or worsening during pregnancy. Postpartum, the rapid decline in estrogen often triggers severe flare-ups, while menopause, marked by a sustained estrogen reduction, frequently correlates with increased disease severity and flare frequency. The review also addresses the profound impact of psoriasis on women's quality of life, including physical discomfort, psychological distress, and social stigma. Additionally, fertility concerns are discussed, as severe psoriasis and associated treatments may increase the risk of adverse pregnancy outcomes. Consideration is given to hormonal therapies, lifestyle modifications, and their effects on psoriasis, underscoring the need for personalized treatment approaches that account for hormonal influences. Understanding these hormonal dynamics is essential for developing targeted, effective management strategies that enhance quality of life for women affected by psoriasis.

Psoriasis is an immune-mediated chronic inflammatory disease associated with multiple factors. To evaluate the extent to which C-reactive protein (CRP) and genetic predisposition affect the incidence of psoriasis.

The cohort study retrieved 420,040 participants without psoriasis at baseline from the UK Biobank. Serum CRP was categorized into two levels: < 2 mg/L (normal) and ≥ 2 mg/L (elevated). The polygenic risk score (PRS) was used to estimate genetic predisposition, and was characterized as low, moderate and high PRS. The possible interaction and joint associations between CRP and PRS were assessed using Cox proportional hazards models.

Participants with high CRP levels had an increased risk of incident psoriasis compared to those with low CRP levels (HR: 1.26, 95% CI: 1.18-1.34). Participants with high CRP levels and high PRS had the highest risk of incident psoriasis [2.24 (95% CI: 2.01, 2.49)], compared with those had low CRP levels and low PRS. Significant additive and multiplicative interaction were found between CRP and PRS in relation to the incidence of psoriasis.

Our results suggest that higher CRP concentration may be associated with higher psoriasis incidence, with a more pronounced association observed in individuals with high PRS for psoriasis. So, clinicians should be aware that the risk of incident psoriasis may increase in general population with high CRP levels and high PRS, so that early investigation and intervention can be initiated.

Ulcerative colitis (UC) and psoriasis are highly correlated clinically; however, it is unclear whether they have a common pathophysiological mechanism. The purpose of this study is to investigate the important molecules and pathways that mediate the coexistence of UC and psoriasis through quantitative bioinformatics analysis of public RNA-sequencing databases. The UC (GSE38713) and psoriasis (GSE30999) datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes were analysed using the "limma" package and their biological functions were investigated using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. The Search Tool for the Retrieval of Interacting Genes database was used to create the protein-protein interaction (PPI) network, which was visualised by Cytoscape. The CytoHubba plugin was used to select the hub genes. The hub genes of psoriasis and UC were verified in GSE75214, GSE78097, GSE14905, and GSE87466. The predicted value of the hub gene was evaluated by the receiver operating characteristic curve (ROC). Gene Set Enrichment Analysis (GSEA) and immune infiltration were performed for the hub genes. Finally, we performed transcription factor (TF)-gene interaction network analysis, TF-miRNA co-regulation network analysis and candidate drug prediction. A total of 114 genes (89 ascending genes and 25 descending genes) with similar expression trends between UC and psoriasis were identified. Enrichment analysis revealed that the two signaling pathways were primarily related to immune and inflammatory responses. PPI network screened 13 hub genes (IL-1B, CXCL10, TLR2, CD274, CXCR2, CXCL9, MMP9, CXCL1, CASP1, IL-7R, IL-1RN, CCL18 and LCN2). Using NetworkAnalyst, we constructed a co-regulatory network diagram of TF-gene and TF-miRNA. Finally, diacerein was predicted to be effective in the treatment of UC and psoriasis. Our research revealed the common pathogenesis of UC and psoriasis, and examined the hub genes, TF and miRNA and potential therapeutic drugs (diacerein). These findings may provide new perspectives for further mechanism research and clinical treatment.

Psoriatic arthritis (PSA) is an inflammatory joint disease associated with psoriasis (PSO) that can be easily missed. Existing PSA screening tools ignore objective serologic indicators. The aim of this study was to develop a disease screening model and the Psoriatic Arthritis Inflammation Index (PSAII) based on serologic data to enhance the efficiency of PSA screening.

A total of 719 PSO and PSA patients from the National Health and Nutrition Examination Survey (NHANES) (as training set and test set) and 135 PSO and PSA patients who were seen at The First Affiliated Hospital of Zhejiang Chinese Medical University (as external validation set) were selected, 31 indicators for these patients were collected as potential input features for the model. Least Absolute Shrinkage and Selection Operator (LASSO) was used to identify PSA-related features. Five models of logistic regression (LR), random forest, k-nearest neighbor, gradient augmentation and neural network were developed in the training set using quintuple cross validation. And we developed PSAII based on the results of LASSO regression and weights of logistic model parameters. All performance metrics are derived on the test set and the external validation set.

Five variables were selected to build models, including age, lymphocyte percentage, neutrophil count, eosinophilic count, and C-reactive protein. In all established models, the LR model performed the best, with an Area Under Curve (AUC) of 0.87 (95% confidence interval (CI): 0.83-0.90) on the test set; on the external validation set the AUC was 0.82 (95%CI: 0.74-0.90). The PSAII formula was PSAII = percentage of lymphocytes × C-reactive protein/(neutrophil count × eosinophilic count × 10). The AUC of PSAII in the test is 0.93 (95%CI: 0.88-0.97), and the cutoff value is 18. The AUC of the external validation set is 0.81 (95%CI: 0.72-0.89).

This study developed and validated five models to assist screening for PSA by analyzing serum data from NHANES and Chinese populations. The LR model demonstrated the best performance. We created PSAII for PSA screening. However, the high false positive rate of PSAII makes it necessary to combine it with other PSA screening tools when applied.

Psoriasis is a common immune-mediated inflammatory skin disease associated with various comorbidities, including obesity.

This study aimed to investigate changes to psoriasis symptoms, severity, and treatment agents in patients undergoing Metabolic and Bariatric Surgery (MBS).

Rasool-E Akram University Hospital.

This prospective observational study consisted of 32 adult patients with obesity and psoriasis who underwent MBS (e.g., Roux-en-Y gastric bypass, One anastomosis gastric bypass, sleeve gastrectomy) between January 2010 and December 2020. Patients with a history of prior MBS were excluded. All patients were examined by a board-certified dermatologist. Psoriasis severity was assessed with the Psoriasis Area and Severity Index (PASI).

The majority of patients were females (n = 29). The mean age of the study population was 46.6 ± 10.8 years, and participants were followed-up for 70.6 ± 29.1 months. A significant decrease in BMI was observed postoperatively from 41.5 ± 4.7 to 30 ± 5.5 kg/m2 (P < .001). PASI score significantly decreased from a median (interquartile range [IQR]) of 3.6 (5.90) to 1.20 (3.45) after MBS (P = .006). The number of patients who reported nail involvement significantly decreased following surgery (P = .039), although no significant difference in joint involvement was noted (P = 1.000).

This study shows that MBS can reduce psoriasis severity and lower the number of needed treatments. Given psoriasis's complexity and varied individual responses, personalized treatment is essential. Further research is necessary to validate these findings in a larger population.

Numerous studies have linked the inflammatory pathway in psoriasis and metabolic disease, while no specific marker defined it. It is worth exploring the association of β2-microglobulin (β2M) in psoriasis severity and comorbidities.

To investigate the correlation between blood β2M level and psoriasis severity, to explore the inflammatory factors influencing the occurrence of psoriasis comorbidities such as arthritis, diabetes, and hypertension.

Ninety-seven psoriasis patients were analyzed in the cohort retrospective study during 12 weeks.

Significantly higher levels of blood β2M and ESR were observed in the group that patients' PASI ≥10 than in the group that PASI <10. Blood β2M level had strong significantly positive correlations with the PASI in Pearson's correlation analysis. In the model that systemic inflammatory factors to find psoriasis comorbidity risk factors, logistic regression analysis showed that blood β2M level was the significant risk factor associated with diabetes and hypertension. High-sensitivity C-reactive protein (hsCRP) was the significant risk factor associated with arthritis.

Patients with a severer psoriasis tended to have higher blood β2M levels and severer inflammatory state. In the systemic inflammation indexes, the level of blood β2M affected the risk of hypertension and diabetes, and hsCRP affected the risk of arthritis in patients with psoriasis.

Inflammatory bowel diseases (IBD) and psoriasis are chronic inflammatory conditions belonging to the heterogeneous group of immune-mediated inflammatory diseases (IMIDs). A significant bidirectional link between these two entities has been observed, conditioning an increased risk of IBD in patients with psoriasis and vice-versa. Biological therapies used for IBD may lead to the occurrence of psoriasis as a "paradoxical reaction." The objective of this study is to analyze the current evidence on the association between psoriasis and IBD, particularly finding case reports of the appearance or aggravation of psoriasis under therapy with interleukin-12/23 (IL-12/23) and IL-23 inhibitors. We conducted comprehensive research to identify studies examining the association between psoriasis and IBD and to find case presentations that reported the appearance or aggravation of psoriasis under biologic therapy with IL-12/23 and IL-23 inhibitors up to March 2024. Clinical trials for IL-12/23 and IL-23 inhibitors in IBD were analyzed to find cases of paradoxical psoriasis as registered adverse events. The sources of evidence are PubMed and ClinicalTrials.gov. For each included case report, data on patient characteristics concerning their age, sex, and comorbidities were selected. Moreover, information regarding the indication for biologic therapy, time to onset of paradoxical psoriasis after starting treatment, clinical presentation, and management of the paradoxical psoriasis was extracted. We found 10 reported cases of ustekinumab-induced new-onset or worsening psoriasis and one reported case of paradoxical psoriasis induced by risankizumab in the literature. Four cases of paradoxical psoriasis have been also registered in clinical trials involving ustekinumab treatment in IBD. Psoriasis can constitute a rare paradoxical adverse event of ustekinumab treatment, but further studies are needed to better clarify the cytokine imbalance that leads to this phenomenon induced by inhibition of IL-12/23 and IL-23. Still, few real-world data exist to draw any conclusions, but risankizumab may positively treat psoriasis induced by ustekinumab.

Several Genome Wide linkage Studies on psoriasis performed to gain insight of genetic architecture of the disease. Caspase Recruitment Domain-containing family 14 (CARD14) also known as CARMA2 or BIMP2; cytogenic location: 17q25.3, is a scaffold protein that primarily controls the skin epidermis's nuclear factor kB (NF-kB) signaling pathway activity in skin epidermis, a master gene for inflammation, has been shown to be linked with rare, heritable form of psoriasis. CARD14 is predominantly expressed in keratinocytes and epithelial cells, but also in unidentified dermal cells. For better understanding of molecular processes involved in CARD14 underlying Indian psoriatic patients, we analyzed gene expression of 42 moderates to severe cases of plaque psoriasis and same number of controls using qPCR and its validation through Immunohistochemistry (IHC). This study identifies that the expression of CARD14 in dermal endothelial cells among patients with psoriasis and explores the potential functional consequences associated with an overactive CARD14 gene. Furthermore, the expression data from the western population was consistent with the results of the qPCR validation of the candidate gene. There is a significant correlation between Indian psoriasis vulgaris patients and CARD14 up-regulation, as evidenced by a roughly two-fold shift in lesional tissue expression. This provides insights into the pathways and genes linked to the pathogenesis of psoriasis.

Psoriasis is a chronic inflammatory skin disease with complex pathogenesis and variable severity. Performed studies have indicated the impact of vitamin D3 deficiency on the pathogenesis of psoriasis and its severity. However, there is no clear evidence of the influence of the mucosal microbiome on the onset and progression of psoriasis. This review aims to present the current evidence on the role of vitamin D3 and colonization of the oral mucosa by Candida yeast-like fungi in the pathogenesis of psoriasis. Candida albicans is a common yeast that can colonize the skin and mucosal surfaces, particularly in individuals with weakened immune systems or compromised skin barriers. In psoriasis, the skin's barrier function is disrupted, potentially making patients more susceptible to fungal infections such as Candida. Since patients with psoriasis are at increased risk of metabolic syndrome, they may experience the vicious circle effect in which chronic inflammation leads to obesity. Vitamin D3 deficiency is also associated with microbiological imbalance, which may promote excessive growth of Candida fungi. Under normal conditions, the intestinal and oral microflora support the immune system. Vitamin D3 deficiency, however, leads to disruption of this balance, which allows Candida to overgrow and develop infections.

Kidney impairment resulting from psoriasis constitutes a serious complication, affecting the overall well-being of patients and necessitating a thorough comprehension for efficient management. Guanylate-binding protein 5 (GBP5) is known to play a role in inflammatory responses, but its function in psoriasis remains unclear and warrants investigation in.

To pinpoint GBP5 as innovative therapeutic target and decipher the underlying mechanisms in kidney impairment resulting from psoriasis.

Skin samples from psoriatic patients were used to detect GBP5 expression through Immunoblot and qPCR. Hacat cells were treated with TNF-α to construct the psoriasis skin cell model. Edu and CCK-8 assays were performed to confirm the effects on cell viability, ELISA was conducted to confirm the effects on inflammation. H&E staining and PASI scocing were conducted to confirm the effects on renal damage. Immunoblot confirmed the mechanism.

GBP5 was highly expressed in psoriasis skin tissues. Ablation of GBP5 reduced tumor necrosis factor alpha (TNF-α)-stimulated growth as well as inflammation in human immortalized keratinocyte (HaCaT) cell. In the imiquimod (IMQ)-stimulated mouse model, GBP5 knockdown alleviated psoriasis symptoms and reduced renal damage. Mechanically, GBP5 depletion suppressed the activation of nuclear factor kappa-light-chain-enhancer of activated B cells-signal transducer and activator of transcription 3 (NF-κB/STAT3) axis.

Inhibiting GBP5 can mitigate the renal injury caused by psoriasis through NF-κB/STAT3 axix.

To systematically evaluate clinical features and effects of cyclosporine in the treatment of psoriasis. Databases including Web of Science, PubMed, The Cochrane Library, Embase, CNKI, Wan Fang, and VIP were electronically searched for studies on the use of cyclosporine in the treatment of psoriasis, from inception to March 2024. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. A meta-analysis was then performed. A total of 12 randomised controlled trial (RCT) studies were included. Compared with the control group, there were statistically significant differences in the effective rate, recurrence rate, erythema regression time, pustular resolution time, fever resolution time, and Psoriasis Area Severity Index (PASI) score of cyclosporine in the treatment of psoriasis. Moreover, the sub-group analysis showed that the effective rate of patients aged less than 40 years was significantly higher than that of the control group and the recurrence rate was significantly lower than that of the control group. The effective rate of psoriasis patients without nail lesions was significantly higher than that of control group. The effective rate of cyclosporin was significantly higher than that of dexamethasone acetate. There was no significant change in pooled sensitivity and specificity after each study was excluded one by one, indicating the stability of the meta-analysis. Cyclosporine had a high effective rate and low recurrence rate in the treatment of psoriasis, but it still had similar rate of adverse reactions compared to other drugs. This study systematically evaluated the effect of cyclosporine in the treatment of psoriasis and provided reference for clinical practice.

CXCL13 is a chemokine that plays an important role in the regulation and development of secondary lymphoid organs. CXCL13 is also involved in the regulation of pathological processes, particularly inflammatory responses, of many diseases. The function of CXCL13 varies depending on the condition of the host. In a healthy condition, CXCL13 is mainly secreted by mouse stromal cells or human follicular helper T cells, whereas in diseases conditions, they are produced by human peripheral helper T cells and macrophages in non-lymphoid tissues; this is termed ectopic expression of CXCL13. Ectopic CXCL13 expression is involved in the pathogenesis of various immune-mediated inflammatory diseases as it regulates the migration of B lymphocytes, T lymphocytes, and other immune cells in inflammatory sites as well as influences the expression of inflammatory factors. Additionally, ectopic expression of CXCL13 plays a key role in ectopic lymphoid organ formation. In this review, we focused on the sources of CXCL13 in different conditions and its regulatory mechanisms in immune-mediated inflammatory diseases, providing novel ideas for further research on targeting CXCL13 for the treatment of immune-mediated inflammatory diseases.

Psoriasis is a chronic inflammatory condition mediated by the immune system with various manifestations. The increased prevalence of subclinical joint involvement has led to the development of early diagnostic methods for psoriatic arthritis, including several instruments that have been validated and used in clinical practice. The aim of this study was to perform the Romanian translation, cultural adaptation, and validation of three assessment tools: the Early Arthritis for Psoriatic Patients (EARP) Questionnaire, Psoriasis Epidemiology Screening Tool (PEST), and Toronto Psoriatic Arthritis Screen 2 (TOPAS 2), which are designed to evaluate early-stage arthritis in patients with psoriasis.

All the activities were carried out in accordance with the internationally recognized methodology recommended by the International Society for Pharmacoeconomics and Outcome Research (ISPOR), the recommendations of the World Health Organization (WHO) regarding the translation process and the validation of instruments, and data from the international literature. These three questionnaires were administered to 29 patients with psoriasis diagnosed by biopsy. A descriptive study was conducted and the data were analyzed with appropriate statistical tests using the PSPP program. A reliability test was assessed using Cronbach's alpha coefficient.

The obtained values were significant for the first two questionnaires, with a value of 0.89 for the EARP and 0.63 for the PEST, but the value was not as significant for ToPAS2, at 0.40.

This pilot study revealed that the Romanian and original versions of the three questionnaires are similar.

Psoriasis is a chronic skin disease characterized by abnormal proliferation and inflammation of epidermal keratinocytes. Fibroblast growth factor 12 (FGF12) is implicated in the regulation of diverse cellular signals; however, its precise mechanism in psoriasis requires further investigation. In this study, high expression of FGF12 is observed in the epidermis of skin lesion in psoriasis patients and imiquimod (IMQ)-induced psoriasis like-dermatitis. Moreover, specific loss of FGF12 in keratinocytes in IMQ-induced psoriasis model alleviates psoriasis-like symptoms and reduces proliferation. In vitro RNA sequencing demonstrates that knockdown of FGF12 effectively arrests the cell cycle, inhibits cell proliferation, and predominantly regulates the p53 signaling pathway. Mechanistically, FGF12 is selectively bound to the RING domain of MDM2, thus partially inhibiting the binding of β-Trcp to MDM2. This interaction inhibits β-Trcp-induced-K48 ubiquitination degradation of MDM2, thereby suppressing the activity of the p53 signaling pathway, which results in excessive cell proliferation. Last, the alleviatory effect of FGF12 deficiency on psoriasis progression is reversed by p53 knockdown. In summary, these findings provide valuable insights into the mechanisms by which FGF12 suppresses p53 signaling in keratinocytes, exacerbating the development of psoriasis. This positive regulatory loop highlights the potential of FGF12 as a therapeutic target to manage psoriasis.

Psoriasis is a prevalent condition characterized by chronic inflammation, immune dysregulation, and genetic alterations, significantly impacting the well-being of affected individuals. Recently, a novel aspect of programmed cell death, ferroptosis, linked to iron metabolism, has come to light. This research endeavors to unveil novel diagnostic genes associated with ferroptosis in psoriasis, employing bioinformatic methods and experimental validation. Diverse analytical strategies, including "limma," Weighted Gene Co-expression Network Analysis (WGCNA), Least Absolute Shrinkage and Selection Operator (LASSO), Support Vector Machine Recursive Feature Elimination (SVM-RFE), and Random Forest (RF), were employed to pinpoint pivotal ferroptosis-related diagnostic genes (FRDGs) in the training datasets GSE30999, testing dataset GSE41662 and GSE14905. The discriminative potential of FRDGs in distinguishing between normal and psoriatic patients was gauged using Receiver Operating Characteristic (ROC) curves, while the functional pathways of FRDGs were scrutinized through Gene Set Enrichment Analysis (GSEA). Spearman correlation and ssGSEA analysis were applied to explore correlations between FRDGs and immune cell infiltration or oxidative stress-related pathways. The study identified six robust FRDGs - PPARD, MAPK14, PARP9, POR, CDCA3, and PDK4 - which collectively formed a model boasting an exceptional AUC value of 0.994. GSEA analysis uncovered their active involvement in psoriasis-related pathways, and substantial correlations with immune cells and oxidative stress were noted. In vivo, experiments confirmed the consistency of the six FRDGs in the psoriasis model with microarray results. In vitro, genetic knockdown or inhibition of MAPK14 using SW203580 in keratinocytes attenuated ferroptosis and reduced the expression of inflammatory cytokines. Furthermore, the study revealed that intercellular communication between keratinocytes and macrophages was augmented by ferroptotic keratinocytes, increased M1 polarization, and recruitment of macrophage was regulated by MAPK14. In summary, our findings unveil novel ferroptosis-related targets and enhance the understanding of inflammatory responses in psoriasis. Targeting MAPK14 signaling in keratinocytes emerges as a promising therapeutic approach for managing psoriasis.

Psoriasis is an autoimmune inflammatory skin disease, featuring microvascular abnormalities and elevated levels of bradykinin. Contact activation of Factor XII can initiate the plasma kallikrein-kinin cascade, producing inflammation and angioedema. The role of Factor XII in psoriasis is unknown.

The effects of deficiency of Factor XII or its enzymatic substrate, prekallikrein, were examined in the imiquimod-induced mouse model of psoriasis. Skin microcirculation was assessed using intravital confocal microscopy and laser Doppler flowmeter. A novel antibody blocking Factor XII activation was evaluated for psoriasis prevention.

Expression of Factor XII was markedly up-regulated in human and mouse psoriatic skin. Genetic deletion of Factor XII or prekallikrein, attenuated imiquimod-induced psoriatic lesions in mice. Psoriatic induction increased skin microvascular blood perfusion, causing vasodilation, hyperpermeability and angiogenesis. It also promoted neutrophil-vascular interaction, inflammatory cytokine release and enhanced Factor XII / prekallikrein enzymatic activity with elevated bradykinin. Factor XII or prekallikrein deficiency ameliorated these microvascular abnormalities and abolished bradykinin increase. Antagonism of bradykinin B2 receptors reproduced the microvascular protection of Factor XII / prekallikrein deficiency, attenuated psoriatic lesions, and prevented protection by Factor XII / prekallikrein deficiency against psoriasis. Furthermore, treatment of mice with Factor XII antibody alleviated experimentally induced psoriasis and suppressed microvascular inflammation.

Activation of Factor XII promoted psoriasis via prekallikrein-dependent formation of bradykinin, which critically mediated psoriatic microvascular inflammation. Inhibition of contact activation represents a novel therapeutic strategy for psoriasis.

Psoriasis is a chronic and recurrent inflammatory skin disease characterized by abnormal proliferation and differentiation of keratinocytes and activation of immune cells. However, the molecular driver that triggers this immune response in psoriatic skin remains unclear. The inflammation-related gene absent in melanoma 2 (AIM2) was identified as a susceptibility gene/locus associated with psoriasis. In this study, we investigated the role of AIM2 in the pathophysiology of psoriasis. We found elevated levels of mitochondrial DNA in patients with psoriasis, along with high expression of AIM2 in both the human psoriatic epidermis and a mouse model of psoriasis induced by topical imiquimod (IMQ) application. Genetic ablation of AIM2 reduced the development of IMQ-induced psoriasis by decreasing the production of type 3 cytokines (such as IL-17A and IL-23) and infiltration of immune cells into the inflammatory site. Furthermore, we demonstrate that IL-17A induced AIM2 expression in keratinocytes. Finally, the genetic absence of inflammasome components downstream AIM2, ASC, and caspase-1 alleviated IMQ-induced skin inflammation. Collectively, our data show that AIM2 is involved in developing psoriasis through its canonical activation.

Psoriasis is a troublesome scaling skin disease with no high-effective medication available by far. Signal transducer and activator of transcription 3 (STAT3) has recently been revealed as a crucial player in the pathogenesis and progression of psoriasis and emerged as an intriguing antipsoriatic drug target. Naturally occurring lapachol and its quinone analogs had been discovered as effective STAT3 inhibitors, however, their antipsoriatic effects are not well investigated. Previously, we have reported a series of isothiazoloquinone lapachol derivatives. Here, the antipsoriastic potentials of these isothiazoloquinones were investigated and, in addition, 35 novel isoxazoloquinone derivatives were prepared and studied for their anti-psoriasis properties. Among them, the most potent antipsoriatic compound B20 determined by in vitro test on HaCaT cells could directly bind to STAT3, reduce STAT3 level and inhibit STAT3 nuclear translocation. In vivo studies showed that topical application of B20 could effectively alleviate IMQ-induced psoriasis in mice with no obvious side effects. In addition, B20 inhibited the production of interleukin 17 (IL-17A), a STAT3-downstream cytokine essential for the progression of psoriasis, both in vitro and in vivo. Thus, isoxazoloquinone B20 is a potent STAT3-targeting antipsoriatic agent worth of further investigation.