Localized delivery of indoleamine 2,3-dioxygenase (IDO) conjugated microgels reduced psoriatic scores compared to soluble IDO or unconjugated microgels.

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Enzyme therapeutics are often limited by poor stability, rapid clearance, and systemic effects that reduce therapeutic efficacy and necessitate high dosing. Enzyme-biomaterial conjugation can address these limitations and improve outcomes by localizing therapeutics at the tissue site of intended action. In particular, indoleamine 2,3-dioxygenase (IDO), a potent immunomodulatory enzyme, has demonstrated therapeutic effectiveness when retained locally at sites of inflammation through fusion to a carbohydrate-binding protein.

Here, we report a complementary biomaterial-mediated delivery strategy to prolong retention time and investigate efficacy in an imiquimod-induced model of psoriasis. IDO maintained enzyme activity after bioconjugation to polyethylene glycol maleimide (PEG-MAL) microgels. Localized delivery of IDO-conjugated microgels reduced psoriatic scores compared to soluble IDO or unconjugated microgels. Additionally, fibrotic capsule thickness decreased 30% in the IDO-conjugated microgel group compared to the unconjugated microgel.

These findings demonstrate the efficacy of localized IDO delivery via covalent attachment to granular hydrogels, which may serve as a platform for other immunomodulatory enzymes.

This study demonstrates that pantethine modulates pathogenic cell communication and signalling networks in psoriasis.

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Psoriasis is a chronic inflammatory skin disease characterized by disrupted epidermal homeostasis driven by interconnected immuno-inflammatory, metabolic, and redox signalling networks. Vesicle-associated intercellular communication has emerged as an important contributor to inflammatory amplification and tissue remodelling within the epidermal microenvironment. Pantethine, a stable vitamin B5 derivative with lipid-modulatory and anti-inflammatory properties, has been implicated in regulation of cellular stress responses and membrane-associated signalling pathways, suggesting potential therapeutic relevance in psoriasis.

Here, we investigated the effects of pantethine using a full-thickness 3D human psoriatic skin model following keratinocyte safety assessment. Integrated histopathological, immunohistochemical, quantitative RT-PCR, and proteomic analyses were employed to interrogate inflammatory, oxidative, proliferative, apoptotic, differentiation-associated and vesicle-related responses. Pantethine significantly reduced epidermal thickening and normalized multiple psoriasis-associated molecular signatures. Proteomic profiling revealed coordinated modulation of vesicle-associated, cytoskeletal and extracellular matrix-related proteins, accompanied by reduced expression of exosome-associated markers CD63 and CD9. Pantethine suppressed pro-inflammatory signalling involving IL-1β, TNF-α, IL-17, S100 family members, and hyperproliferative keratin-associated pathways while reducing caspase-3–associated apoptotic activity.

Concurrently, pantethine enhanced antioxidative and immunoregulatory responses through activation of Nrf-2 and TGF-β, restored differentiation and barrier-related markers including filaggrin, caspase-14, and involucrin, and reduced hypoxia- and tissue-remodelling–associated mediators including HIF-1α, VEGF, COL6A3, and COL1A2. Network-based proteomic analyses further identified computationally inferred associations with SLIT/ROBO-related pathways, although these associations require further functional validation. Collectively, these findings support pantethine as a promising candidate that modulates vesicle-associated proteins together with inflammatory and tissue-remodelling responses involved in epidermal homeostasis.

Joining: For the moment the forum is closed for new member registrations, due to some maintenance work. But if you do want to join Psoriasis Club please check back often, we can't give an exact date for when we will be able to welcome new members but hopefully by the end of next week.

Reading: Guests can read the public boards as normal, members can read the members boards by logging-in.

Posting: Members can log-in and post or do other things much the same as it was and you can change the way it looks in your User CP.

Sorry for any convenience, hope the psoriasis didn't flare up but well be back soon.

People with psoriasis often start with creams to sooth the skin, I have often reported about so-called naturel products having illegal potent topical corticosteroids. So you would think going to a pharmacy for over the counter products would be a safe bet, but this US research suggest differently.

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Introduction:
Skin conditions affect approximately 85 million individuals in the US alone. Numerous over-the-counter (OTC) skin products marketed online claim benefit for conditions such as psoriasis, eczema, and hyperpigmentation despite lacking clinically proven active ingredients. We and others, including regulatory agencies such as the US Food and Drug Administration (FDA), previously identified undeclared pharmacologically active ingredients (UPAIs) in OTC skin products, including potent topical corticosteroids at pharmacologically active doses. Such ingredients may explain apparent efficacy but may also pose substantial risks when used without medical supervision. To our knowledge, no widely adopted standardized approach exists to systematically identify UPAIs in OTC skin products. We performed a targeted assessment for the presence of UPAIs in 18 OTC skin products marketed online.

Methods:
This quality improvement study did not involve human participants and therefore did not require IRB approval or informed consent. Skin products were purchased from major online retail platforms and selected using predefined criteria: efficacy claims for inflammatory or persistent skin conditions, including dermatitis, psoriasis, eczema, or hyperpigmentation; absence of listed clinically proven ingredients for these conditions; and consumer engagement, defined as 100 or more reviews on at least 1 platform. Products with prior reports of UPAIs or branding or labeling characteristics similar to those of previously identified products were included if they met at least 1 criterion. Analytical screening for 28 corticosteroids and antifungals was performed using high-resolution liquid chromatography–mass spectrometry with tandem mass spectrometry confirmation as previously described methods. Products were purchased from February through December 2025 and analyzed from April 2025 through April 2026. When a UPAI was detected, 2 additional units of the same product were purchased and analyzed, resulting in 3 samples evaluated per product. At the time of analysis, review counts were also recorded from online platforms on which products were identified.

Results:
UPAIs were identified in 6 of 18 preselected products (33.3%) and in all 3 analyzed units of each positive product. The superpotent (class I), prescription-only corticosteroid clobetasol propionate was detected in 6 products (33.3%), 2 of which additionally contained the antifungals miconazole or terbinafine. Detected concentrations of clobetasol propionate ranged from approximately 0.01% to 0.46%, with the highest concentrations exceeding those in FDA-approved topical formulations (0.05%) by 9.2 fold None of these clinically proven active ingredients were disclosed on product labels. Products that tested positive had more than 10 000 combined user reviews across online retail platforms.

These threads have been deemed worth reading, if you have a suggestion please let me know.

Vitamin D the natural way.

The anti-inflamatory food pyramid

Harmful Ingredients in Skincare Products

Aloe vera scam

Free Psoriasis Treatment

Watch out for the Scams!

Here is a list of the most common topical treatments for psoriasis, if anyone wants more added please let me know.

Synalar

Dovobet And Dovonex (What's the difference ?)

Enstilar foam

Could targeting macrophage cannabinoid 1 receptor (CB1R) be a new therapeutic strategy for psoriasis ?

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Psoriasis is a chronic inflammatory skin disease associated with systemic metabolic dysregulation; however, the molecular pathways linking metabolic signaling to skin inflammation remain poorly understood. Here, we identify cannabinoid 1 receptor (CB1R) in macrophages as a key immunometabolic regulator of psoriatic inflammation and a potential therapeutic target.

CB1R expression was increased in macrophages infiltrating psoriatic lesional skin in both humans and mice, and both pharmacological inhibition and genetic deletion of CB1R markedly attenuated psoriasis-like pathology in mouse models by reducing epidermal hyperplasia, inflammation, and barrier dysfunction in a macrophage-dependent manner.

Mechanistically, CB1R signaling in macrophages suppressed expression of the RNA-binding protein AUF1, leading to stabilization of Nlrp3 mRNA and enhanced NLRP3 inflammasome activation. AUF1 directly bound an AU-rich region within the Nlrp3 3′ untranslated region and promoted mRNA destabilization, thereby limiting inflammasome activation and IL-1β production. Restoration of AUF1 expression, either by CB1R inhibition or overexpression, reduced NLRP3 levels and alleviated psoriasis-like pathology, whereas Nlrp3 deficiency abrogated these effects.

Collectively, these findings define a CB1R–AUF1–NLRP3 signaling axis that links metabolic signaling to inflammasome-driven skin inflammation in macrophages. Targeting macrophage CB1R may therefore represent a promising therapeutic strategy for psoriasis and other immunometabolic inflammatory diseases.

New Phase 3b data on Lilly's Taltz (ixekizumab) and Zepbound (tirzepatide) advance understanding of the interconnected immune and metabolic biology in adults with psoriasis and obesity.

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Eli Lilly and Company announced new exploratory data from the TOGETHER-PsO Phase 3b clinical trial evaluating the concomitant use of Taltz (ixekizumab) and Zepbound (tirzepatide) compared with Taltz alone in adults with moderate-to-severe plaque psoriasis and obesity or overweight with at least one additional weight-related comorbid condition. The prespecified analysis, presented at the 2026 Fall Clinical Dermatology Conference in Las Vegas, provides new insights suggesting an immunometabolic relationship between psoriasis and obesity. These data showed that when Taltz and Zepbound were used together, changes were observed in more psoriasis disease-associated and metabolic biomarkers compared to Taltz monotherapy. In the U.S., approximately 61% of people with psoriasis also have obesity or overweight with at least one weight-related comorbidity.

"People living with psoriasis and obesity carry a compounded burden that extends beyond what is visible, yet these conditions are too often viewed through separate treatment lenses," said Mark Genovese, M.D., senior vice president of Lilly Immunology development. "The broader biomarker changes observed with Taltz and Zepbound, including those associated with skin clearance, may point to a meaningful relationship between immune and metabolic biology. Along with previously reported clinical outcomes, these findings support a more comprehensive approach to psoriasis care that also addresses obesity for people managing both conditions."

This analysis examined circulating proteins and gene expression in the blood to better understand the biological change observed when patients were treated concomitantly with Taltz and Zepbound vs. Taltz alone. At Week 36, observed changes in psoriasis-specific, immune and metabolic biomarkers in both the Taltz and Zepbound and Taltz monotherapy treatment arms were consistent with the known biological effects of each medicine when used for their approved indications. Notably, Taltz and Zepbound used together were associated with broader biomarker responses compared to Taltz alone as early as Week 12. This included changes in more proteins (482 vs. 140 differentially expressed proteins) and genes (467 vs. 16 differentially expressed genes) by Week 36.

Further, the analysis showed greater reductions in inflammatory immune activity with Taltz and Zepbound compared with Taltz alone, including changes related to neutrophils, a type of immune cell involved in inflammation. Changes in a subset of neutrophil-associated markers mediated a portion of the additional Psoriasis Area and Severity Index (PASI) response seen with Taltz and Zepbound vs. Taltz alone.

"This analysis provides new insights into the potential connected immune and metabolic biology in people with psoriasis and obesity," said James G. Krueger, M.D., Ph.D., Professor and Laboratory Head, The Rockefeller University. "What is most compelling is these findings identified differences in inflammatory pathways when patients received concomitant treatment with Taltz plus Zepbound for both conditions. These data at the intersection of psoriasis and obesity highlight immunometabolic health as an important area for continued scientific research."

These data follow previously reported results from TOGETHER-PsO, which showed that Taltz and Zepbound used together delivered superior skin clearance and clinically meaningful weight reduction compared with Taltz alone at the Week 36 primary endpoint. Improvements were maintained or further improved through Week 52, with safety consistent with the known profile of each respective medicine.

This study presents a dual action microneedle therapy for psoriasis that alleviates psoriasis by modulating keratinocyte ferroptosis and scavenging cfDNA to restore inflammatory homeostasis.

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Psoriasis is a chronic inflammatory skin disorder characterized by dysregulated epithelial-immune interactions. Emerging evidence implicates keratinocyte ferroptosis as a critical pathological mechanism, whereby oxidative epidermal damage and elevated levels of cell-free DNA (cfDNA) amplify immune dysregulation and sustain chronic psoriatic inflammation.

Here, we developed a dual-action microneedle system (CAD), with needle tips composed of guanidine-functionalized chitosan and deferoxamine (DFO), designed to eliminate pro-inflammatory cfDNA while locally releasing DFO for iron chelation. In an imiquimod-induced psoriasis mouse model, CAD markedly alleviated psoriatic symptoms, reducing the psoriasis area and severity index score by approximately 50% compared with the model group and demonstrating superior therapeutic efficacy to clinically used calcipotriol.

Further studies revealed that CAD depleted accumulated iron and inflammatory cfDNA in lesioned skin, alleviating oxidative stress and suppressing ferroptosis, inhibiting the inflammatory cascade, and maintaining immune homeostasis for effective psoriasis treatment. This study presents a dual-action microneedle therapy for psoriasis that alleviates psoriasis by modulating keratinocyte ferroptosis and scavenging cfDNA to restore inflammatory homeostasis, providing a promising foundation for the development of mechanism-guided combination therapies for psoriasis.

Future work will further optimize the formulation for clinical translation and explore its therapeutic potential for other ferroptosis-related inflammatory skin disorders.

This study evaluated whether IL-17A and IL-23p19 inhibitors improve psychiatric symptoms in psoriasis patients, and whether these improvements are associated with reductions in inflammatory markers, independently of skin response.

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Background and Objectives:
Psoriasis is a systemic inflammatory disease affecting skin and mental health. Biologic agents targeting IL-17A and IL-23p19 effectively treat skin symptoms, but their psychiatric and systemic anti-inflammatory effects remain unclear, especially in real-life settings. This study evaluated whether IL-17A and IL-23p19 inhibitors improve psychiatric symptoms, and whether these improvements are associated with reductions in inflammatory markers, independently of skin response.

Patients and Methods:
In this multicenter prospective study, 235 psoriasis patients starting IL-17A and IL-23p19 inhibitors were assessed at baseline and six months. Assessments included CRP, NLR, HADS-A, HADS-D, and DLQI scores.

Results:
Treatment significantly improved skin, quality of life, and psychiatric scores (p < 0.001). CRP declined significantly and was independently correlated with reductions in HADS-A and HADS-D scores, even in patients without PASI90 response. IL-23p19 inhibitors produced greater reductions in CRP and NLR compared to IL-17A inhibitors, suggesting broader anti-inflammatory effects through upstream cytokine blockade.

Conclusions:
IL-17A and IL-23p19 inhibitors improve both dermatological and psychiatric outcomes in psoriasis, potentially by reducing systemic inflammation. CRP may serve as a biomarker of psychiatric improvement, independent of skin response. Future studies with longer follow-up and non-biologic control groups are warranted. Integrating dermatological and psychiatric care may enhance outcomes in psoriasis patients.

In this retrospective real-world cohort of patients with moderate-to-severe plaque psoriasis treated with Cosentyx (secukinumab), higher baseline low-density lipoprotein cholesterol (LDL) showed a directionally inverse association.

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Background:
Psoriasis is a systemic inflammatory disease frequently accompanied by cardiometabolic comorbidities. Whether baseline lipid status influences clinical response to interleukin-17A blockade remains insufficiently defined.

Objective:
To evaluate the association between baseline low-density lipoprotein cholesterol (LDL) and week-16 clinical response to secukinumab in patients with moderate-to-severe plaque psoriasis and to describe outcomes under 150-mg and 300-mg dosing regimens in real-world practice.

Methods:
We performed a single-center retrospective cohort study including 325 patients with moderate-to-severe plaque psoriasis who received secukinumab for at least 16 weeks.
Patients received either 150 mg or 300 mg secukinumab at weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter. The primary outcome was achievement of at least 75% improvement in Psoriasis Area and Severity Index (PASI75) at week 16. Propensity score weighting was used to reduce baseline imbalance between dosing groups. The primary association was estimated using multivariable logistic regression with baseline LDL modeled continuously and adjustment for multiple factors. Missing LDL was evaluated using measured-versus-missing comparisons and multiple imputation as a sensitivity analysis.

Results:
After inverse probability weighting, baseline demographic and disease severity variables were generally balanced between dose groups, although residual imbalance in selected laboratory variables remained. Week-16 PASI75 response did not differ significantly between the 150-mg and 300-mg groups after adjustment, while early PASI90 response was more frequent in the 300-mg group and week-16 PASI100 response was more frequent in the 150-mg group. Baseline LDL was inversely associated with PASI75 response at week 16 (ORs per 1 mmol/L increase, 0.696, and 95% CI: 0.497–0.976), and further multiple imputation as a sensitivity analysis confirmed the adjusted OR was 0.718 (95% CI: 0.516–0.999, p = 0.049). Patients with low LDL had a higher PASI75 response rate than those with high LDL (85.2% vs 66.7%). In the 300-mg subgroup, high LDL was associated with lower PASI75 and PASI90 response rates. Secukinumab reduced selected inflammatory and metabolic biomarkers, including CRP, ESR, SCC, glucose, and triglycerides, but LDL and HDL did not show significant improvement over 16 weeks.

Limitations:
This was a retrospective, single-center study with potential residual confounding, missing baseline LDL, a relatively small high-LDL subgroup, retrospectively defined multiplicity families, and the absence of prospective validation.

Conclusions:
Higher baseline LDL was associated with a lower probability of achieving week-16 PASI75 after covariate adjustment. LDL should be considered a hypothesis-generating candidate factor of secukinumab response and may help identify patients who require closer clinical and cardiometabolic monitoring during biologic therapy.

Photo-controlled prodrug strategy can  provide a platform for designing smart drug delivery systems to ameliorate psoriasis-like skin inflammation.

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Smart and efficient drug delivery is always desirable, especially for chronic diseases, such as psoriasis. We developed an ultraviolet B (UVB) light-triggered scaffold, 1,4,2-dioxazol-5-thione (DOT), for the controlled release of hydrogen sulfide (H2S), a pivotal endogenous gaseous signaling molecule with promise for anti-inflammatory and antioxidant therapies.

In the DOT scaffold, the kinetics for H2S release are efficiently tuned by fine-adjusting the electronic properties. Upon photoirradiation, DOT releases carbonyl sulfide (COS), which is rapidly converted to H2S by carbonic anhydrase (CA). Furthermore, the DOT platform is conjugated to the active pharmaceutical ingredient pterostilbene (PTE) to afford a hybrid prodrug, PTE-DOT.

Under UVB irradiation at 308 nm, a standard wavelength for psoriasis phototherapy, PTE-DOT simultaneously released H2S and PTE, thereby exerting combined anti-inflammatory and antioxidant effects in vivo. In the psoriasis mouse model, PTE-DOT effectively reduced epidermal thickening and hyperkeratosis, suppressed the production of key psoriatic inflammatory cytokines, and inhibited the differentiation of Th17 cells in the spleen.

Thus, the photo-controlled prodrug strategy provides a platform for designing smart drug delivery systems to ameliorate psoriasis-like skin inflammation.

In this retrospective cohort of 228 Chinese patients with chronic plaque psoriasis, 52 weeks of Tremfya (guselkumab) treatment was associated with a modest but statistically significant reduction in serum uric acid.

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Background:
Hyperuricemia (HUA) is common in psoriasis, but the effect of selective interleukin (IL)-23 inhibition on serum uric acid (UA) is inconsistent.

Methods:
In this two-center retrospective cohort, 228 adults with chronic plaque psoriasis received guselkumab for 52 weeks. The primary outcome was the change in UA (ΔUA). Secondary outcomes included HUA resolution, new-onset HUA, predictors of baseline HUA and HUA resolution, and the association of ΔUA with Psoriasis Area and Severity Index (PASI) response and change in high-sensitivity C-reactive protein (ΔhsCRP).

Results:
At baseline, 92 patients (40.4%) had HUA. UA decreased in the overall cohort (median ΔUA −10.5 μmol/L; bootstrap 95% CI −19.0 to −3.0; p < 0.001), with the largest reduction among baseline HUA patients (median −35.5 μmol/L; 95% CI −53.5 to −17.0), 32.6% of whom achieved HUA resolution; cohort HUA prevalence fell from 40.4% to 33.3% (McNemar p = 0.023). 10.3% of patients with normal baseline UA developed new-onset HUA. ΔUA correlated weakly with ΔhsCRP but not with PASI change. Male sex and higher BMI independently predicted baseline HUA; lower baseline total cholesterol and higher baseline PASI independently predicted HUA resolution.

Conclusion:
Guselkumab was associated with a statistically significant but modest UA reduction, which was largest in patients with HUA and was independent of skin clearance over 52 weeks, suggesting an ancillary metabolic effect of IL-23 inhibition that warrants prospective confirmation.

Emerging evidence suggests a link between psoriasis (PSO), psoriatic arthritis (PSA), and periodontitis (PE)

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Objectives:
Emerging evidence suggests a link between psoriasis (PSO), psoriatic arthritis (PSA), and periodontitis (PE), similar to other systemic conditions. This study aimed to evaluate the levels of Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans (qPCR), as well as salivary biomarkers RANKL, OPG, Survivin, and IL-17 (ELISA) in individuals with PSO and PSA, compared to non-psoriatic controls with and without PE.

Subjects and Methods:
From a case–control study (n = 655), 192 non-smokers and non-diabetics were randomly selected and divided into six gender-matched groups (n = 32 each): control, PSO, and PSA, with and without PE.

Results:
Higher counts of P. gingivalis, T. forsythia, and T. denticola were found in individuals with PE, particularly in PSA + PE and PSO + PE groups, along with significant intergroup differences in IL-17 and survivin, with higher levels in PSA than PSO and controls. In PSA + PE individuals, OPG, IL-17, and survivin were significantly increased. Positive correlations were observed between RANKL, IL-17, survivin, and clinical periodontal parameters, with negative correlations for OPG (p < 0.001).

Conclusions:
Psoriatic individuals with PE show higher levels of classical red-complex periodontopathogens and heightened inflammatory biomarker levels, especially in PSA. These findings highlight the need for integrated care between dermatologists and periodontists.

This study looked at Generalised Pustular Psoriasis (GPP) and mortality risk in English patients.

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Generalised Pustular Psoriasis Epidemiology Assessed

Generalised pustular psoriasis (GPP) prevalence increased by more than 50% in England between 2008 and 2022, while patients with GPP had substantially higher mortality risk and reduced life expectancy compared with people without the condition.

The population-based cohort study used primary care and hospital records linked with mortality, ethnicity and deprivation data. Among 25.8 million people, 991 patients with GPP were identified, of whom 63% were female, 86% were White, 10% were Asian and 3% were Black, Mixed or Other.

GPP prevalence increased from 20.9 per million in 2008 to 32.5 per million in 2022. Incidence remained stable until 2016 before increasing, reaching 4.9 per million person-years. The mean age at GPP onset was 51.4 years, with onset occurring earlier among Asian patients than White patients.

Mortality Risk Increased With GPP

Patients with GPP had more than three times the risk of all-cause mortality compared with people without GPP (adjusted hazard ratio [aHR]: 3.19; 95% confidence interval [CI]: 2.58–3.91).

Mortality rates were also elevated for several specific causes of death, including neoplasms, respiratory, digestive and circulatory diseases. The strongest association was observed for sepsis, for which the mortality risk was substantially higher among patients with GPP (aHR: 9.76; 95% CI: 4.92–19.35).

The study also identified differences in GPP prevalence by sex, ethnicity and age. Prevalence was higher among females, Asian people and older age groups, highlighting variation in the epidemiology of the condition across population groups.

Earlier GPP Diagnosis Linked to Life Years Lost

Life expectancy was reduced among patients with GPP, with a younger age at diagnosis associated with the greatest reduction in expected lifespan.

The researchers concluded that the increasing prevalence, differences by sex and ethnicity, and elevated mortality risk demonstrated a substantial clinical burden associated with GPP. They highlighted the need for targeted strategies to reduce preventable morbidity and mortality.

The observational design identifies associations rather than establishing that GPP directly caused the reported mortality outcomes. The findings nevertheless provide population-level data on the epidemiology and mortality burden of GPP in England over a 15-year period.

Hi everyone I’m new to this forum,  I am 70 years old old and it looks like  I am suffering from  some form of psoriasis, not been officially diagnosed yet, have to wain until early November to see a dermatologist,  have   Red  blotches on my forehead face neck backs of, also  itching to my scalp,  backs of hands forearms neck shoulders and back small round red scales very itchy, this all came on  over the last 3 months, not sure of the trigger maybe because I am on beta blockers or too much time in the sun, so that’s me, would welcome any suggestions to  stop the itching (driving me insane). Started using ice packs ? Thanks for looking.

Findings uncover a novel pathogenic mechanism in psoriasis, wherein Calcium-binding protein 39 (CAB39) K196 decrotonylation drives keratinocyte dysfunction.

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Psoriasis is a chronic and recurrent inflammatory dermatosis characterized by dysregulated keratinocyte proliferation. Calcium-binding protein 39 (CAB39), a critical regulatory scaffold for Sterile 20 kinase, has been implicated in multiple diseases, but its role and regulatory mechanisms in psoriasis remain unclear.

Here, we found that CAB39 was significantly upregulated in psoriatic lesions, and CAB39 knockdown inhibited keratinocyte proliferation and attenuated psoriasis progression. Further investigations revealed that CAB39 crotonylation at lysine 196 was reduced in psoriatic lesions. Functional analyses in normal human epidermal keratinocytes (NHEKs) showed that the crotonylation-deficient CAB39 K196A mutant significantly promoted keratinocyte hyperproliferation and glycolytic remodeling.

Dysregulation of modifying enzymes, including downregulated CBP and upregulated HDAC2/3, drives CAB39 K196 decrotonylation in psoriasis. Mechanistically, CAB39 K196 decrotonylation weakens its binding affinity to STRAD (STE20-related adaptor), disrupts the stability of the CAB39-STRAD-LKB1 (liver kinase B1) complex, and inhibits the LKB1/AMPK signaling pathway. Concurrently, decrotonylated CAB39 promotes phosphatidic acid (PA, a lipid second messenger) synthesis, activating the pro-proliferative PA/MAPK/mTOR signaling cascade.

Our findings uncover a novel pathogenic mechanism in psoriasis, wherein CAB39 K196 decrotonylation drives keratinocyte dysfunction, and expand our understanding of non-histone crotonylation in inflammatory skin diseases. Importantly, targeting the CBP/HDAC2/3-CAB39 crotonylation axis may represent a potential therapeutic strategy for psoriasis.

This months poll above asks: Do you talk to others about psoriasis ?

Voting is open to members and guests, our members can also leave a comment if they wish.

This study aimed to determine whether the short-term response to biologics in biologic-naive psoriatic arthritis (PsA) is better in patients initiating biologic treatment early in the disease course.

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Objective:
We aimed to determine whether the short-term response to biologics in biologic-naive psoriatic arthritis (PsA) is better in patients initiating biologic treatment early in the disease course.

Methods:
Patients with PsA who started on biologic therapy from the year 2000 to 2025 were included for analysis. Patients were considered in the early treatment group if they had started on biologic therapy within two years of PsA diagnosis; otherwise, they were considered in the delayed treatment group. The primary outcome was ≥50% reduction in the Disease Activity Index for Psoriatic Arthritis (DAPSA) score at six months. The secondary outcome was Psoriasis Area and Severity Index (PASI) 75, defined as ≥75% improvement in the PASI score at six months. Logistic regression was used to examine the association between early treatment and disease outcomes at six months. Propensity scores were used to account for differences between the groups at the baseline visit.

Results:
Of the 228 included patients, 71 patients were in the early treatment group, and 157 patients were in the delayed treatment group. There were significant differences in the time from PsA diagnosis to biologic treatments over the decades. The propensity score regression adjusted analysis did not suggest a difference in response at six months between those treated within two years of diagnosis and those treated later.

Conclusion:
Short-term response to biologic therapy in patients with PsA does not appear to differ between those treated early or later in the disease course. It remains to be determined whether early treatment prevents progression of joint damage in the longer-term.

Results from clinical field tests to evaluate cardiorespiratory fitness in psoriatic arthritis patients.

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Objective:
Cardiorespiratory fitness (CRF) is reduced in patients with psoriatic arthritis (PsA), highlighting the need for a consistent assessment of CRF in clinical practice. This study aimed to examine the associations between outcomes of clinical field tests, namely six-minute walk test (6MWT) and handgrip strength (HGS), and CRF, as well as to evaluate the accuracy of these clinical field tests in detecting impaired CRF in patients with PsA.

Methods:
Distance walked during 6WMT (six-minute walk distance [6MWD]), HGS by hand dynamometry, and maximal CRF as peak oxygen uptake (VO2peak, milliliters per minute per kilogram) by cardiopulmonary exercise testing were assessed. 6MWD and HGS were compared to reference charts of the general population using one-sided t-tests. Spearman rank correlation coefficients (rs), multivariable linear regression models, and receiver operating curves were analyzed to study associations.

Results:
In 80 patients with PsA, 6MWD was strongly associated with VO2peak (rS = 0.65, P < 0.001), with the multivariable linear regression model, consisting of 6MWD and 6MWT heart rate response and adjusted for relevant covariates, explaining 70% of variance in VO2peak. The threshold of 108% predicted 6MWD had sensitivity of 75% and specificity of 64% to identify patients with impaired CRF. 6MWD and HGS were not significantly decreased compared to the general population (P > 0.05). A higher 6MWD was moderately to strongly correlated with more favorable outcomes regarding disease activity, cardiometabolic risk, and patient-reported outcomes. No or only weak associations between HGS and VO2peak as well as clinical outcomes were noted.

Conclusion:
6MWD was strongly associated with VO2peak, was moderately to strongly correlated with important clinical outcomes, and had adequate accuracy to detect patients with impaired CRF.