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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.

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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.

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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.

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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.

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Psoriasis is a chronic autoimmune skin disease affecting 2%–3% of the global population. Existing therapies, including topical agents, systemic immunosuppressants, and phototherapy, often suffer from limited efficacy, skin irritation, or serious side effects, highlighting the urgent need for more effective and safer alternatives.

Notably, restoring the dynamic balance between regulatory T (Treg) cells and T helper 17 (Th17) cells has emerged as a promising strategy for halting psoriatic progression. Here, we developed a redox-responsive nanoparticle-based topical hydrogel, PB-MJ@N/G, that co-delivers morin (a natural PPARγ activator that promotes Treg proliferation) and JPH203 (a LAT1 inhibitor that suppresses Th17 cell expansion) to modulate the Treg/Th17 balance in psoriatic skin.

These drugs were co-loaded into PLA nanoparticles and further coated with bilirubin-conjugated poly-L-lysine (PB), enabling surface charge reversal and promoting local skin association and nanoparticle-associated delivery into psoriatic skin. In response to the oxidative microenvironment, oxidation-associated changes in the bilirubin-containing PB coating increased its hydrophilicity and facilitated accelerated local drug release. In both in vitro and in vivo models, PB-MJ@N significantly restored the Treg/Th17 ratio, alleviated psoriatic inflammation, and attenuated relapse-associated lesion development in a recurrence model.

This topical, stimuli-responsive nanoparticle presents a powerful immunotherapeutic strategy for psoriasis, supporting sustained treatment-associated benefit.

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Alumis announced topline results from the ongoing ONWARD3 long-term extension (LTE) study. Data confirm envudeucitinib delivered leading skin clearance and the highest reported Psoriasis Area and Severity Index (PASI) 100 response rates among existing and investigational oral therapies. Envudeucitinib is an investigational, next-generation oral TYK2 inhibitor precision-engineered for maximal 24-hour target inhibition.

“Envudeucitinib delivered consistently high rates of skin clearance in the Phase 3 trials, and the long-term data show that the vast majority of patients maintained these strong responses through 48 weeks, with the number of patients achieving completely clear skin continuing to rise over time,” said Dr. Mark Lebwohl, Dean for Clinical Therapeutics at the Icahn School of Medicine at Mount Sinai. “These data, coupled with a consistent safety profile, suggest that envudeucitinib can deliver the durable, reliable disease control physicians and patients are seeking from an oral therapy.”

A total of 1,509 patients entered ONWARD3 from ONWARD1 or ONWARD2, reflecting a robust rollover rate of >85%. A non-responder imputation (NRI) analysis was conducted in 773 of these patients from the envudeucitinib arms who received up to 48 weeks of continuous treatment (24 weeks in ONWARD1/2 and up to 24 weeks in ONWARD3). Topline results include:

• 75% and 54% of patients achieved PASI 90 and PASI 100, respectively
  
• Among patients who entered ONWARD3 with PASI 90 and PASI 100 responses, approximately 90% and 80%, respectively, sustained their skin clearance for the reported duration of the extension study
  

Results from a separate integrated NRI analysis across the ONWARD program (ONWARD1/2 and 3)—evaluating 890 patients originally randomized to envudeucitinib in ONWARD1/2, including those who did not transition into ONWARD3—demonstrated that 66% and 47% of patients who received 48 weeks of envudeucitinib achieved PASI 90 and PASI 100, respectively.

Treatment with envudeucitinib in ONWARD3 continued to be well tolerated, with a safety profile consistent with ONWARD1/2 and no new safety signals observed.

“Far too many people with psoriasis remain undertreated or untreated, and without meaningful skin clearance, this systemic disease continues to limit daily life,” said Leah M. Howard, J.D., President and CEO of the National Psoriasis Foundation. “We are excited for the potential of a new oral therapy that may offer the sustained control patients need to get back to living fully. Restoring those everyday moments is part of what real progress looks like.”

“These long-term data, including the robust 54% PASI 100 response, further validate the strength of envudeucitinib’s precision-engineered design for continuous, maximal TYK2 inhibition and underscore its highly competitive clinical profile,” said Dr. Jörn Drappa, Chief Medical Officer of Alumis. “This level of performance reinforces envudeucitinib’s potential to become a leading oral therapy for moderate-to-severe plaque psoriasis and a 'pipeline-in-a-pill' for immune-mediated diseases driven by IL-23, IL-17, and Type I interferon pathways.”

Alumis plans to present additional results from the ONWARD program at upcoming medical meetings and to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration seeking approval for envudeucitinib for the treatment of moderate-to-severe plaque psoriasis in the fourth quarter of this year. Topline data from the LUMUS Phase 2b trial of envudeucitinib in systemic lupus erythematosus is expected in the third quarter of 2026.

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Background:
Both psoriasis and overactive bladder (OAB) are considered systemic conditions that share many inflammatory or immune pathways in the pathogenesis. One previous study found patients with psoriatic arthritis (PsA) reported significantly higher bladder autonomic dysfunction scores compared to controls. But it is currently unclear whether there is an association between psoriasis and OAB.

Objective:
To assess the association between psoriasis and OAB among US population.

Methods:
This cross-sectional, population-based study utilized representative data of US adults aged 20 –59 years from the National Health and Nutrition Examination Survey (NHANES) 2005–2006 and 2009–2014 cycles. The Overactive Bladder Symptom Score (OABSS) was used to define OAB and group its severity into none, mild, moderate, and severe. Weighted logistic regression models were constructed to investigate the association between psoriasis with OAB or OAB severity. Subgroup analyses were performed to identify whether certain factors could influence the relationship. Sensitivity analyses were further conducted to assess the robustness of our findings.

Results:
Among 11,643 participants, 50.95% were male and the mean age at recruitment was 39.67 (11.55) years. The prevalence of psoriasis increased with OAB severity (2.34% [none], 3.01% [mild], 5.13% [moderate], 5.33% [severe]; p = 0.0008). In weighted logistic regression models, psoriasis was significantly associated with OAB (OR = 1.88, 95% CI: 1.32–2.68) after adjusting all covariates, as well as the severity of OAB. Subgroup analyses indicated that the association was stronger among younger participants, males, participants with obesity or hypertension, and those without diabetes or cardiovascular disease (CVD); conversely, no significant associations were observed in participants with pre-diabetes, diabetic mellitus, or CVD. Sensitivity analyses confirmed the robustness of these findings.

Conclusion:
This study demonstrates a significant association between psoriasis and OAB, with a positive correlation to OAB severity, underscoring the need for early identification and management of OAB symptoms in psoriasis patients to improve overall patient outcomes and enhance their quality of life.

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Background:
Tyrosine kinase 2 (TYK2), a key part of the inflammatory cascade responses, plays an integral role in the pathogenesis of psoriasis. Socrodeucitinib, an oral, TYK2 allosteric inhibitor, selectively inhibits TYK2 cytokine signalling pathways in psoriasis pathogenesis.

Objectives:
To evaluate the efficacy and safety of socrodeucitinib in patients with moderate-to-severe plaque psoriasis.

Methods:
In this phase 2, double-blind, placebo-controlled trial, 125 patients were randomly assigned (1:1:1) to receive socrodeucitinib at 6 mg, 12 mg or placebo orally, once daily, for 12 weeks. The primary endpoint was the proportion of patients with a 75% or greater reduction from the baseline in the Psoriasis Area and Severity Index (PASI) score at week 12.

Results:
At week 12, significantly more patients treated with socrodeucitinib achieved a 75% reduction from baseline in PASI score compared with placebo (28.6% at 6 mg, 72.1% at 12 mg vs. 7.5% for placebo, p < 0.05 and p < 0.001, respectively). At the 12 mg dose, socrodeucitinib resulted in significantly higher response rates compared to placebo, with 46.5% of patients achieving PASI 90 (p < 0.001) and 11.6% achieving PASI 100 (p < 0.05). The treatment of socrodeucitinib also led to significantly higher proportions of patients achieving sPGA responses of 0 or 1 compared to placebo: 33.3% at 6 mg and 65.1% at 12 mg versus 10% for placebo (p < 0.05 and p < 0.001, respectively). Most common adverse events included upper respiratory tract infection which demonstrated a certain dose dependency. Most treatment-related adverse events were mild or moderate, and serious adverse events were infrequent, with no clinically meaningful abnormal trend in laboratory parameters.

Conclusions:
Socrodeucitinib demonstrated significantly greater clearing of psoriasis plaques compared to placebo in patients with moderate-to-severe plaque psoriasis and illustrated a favourable safety and tolerability profile, warranting further investigation in longer-duration and larger trials.

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B-LIAN-S HERBAL CREAM 百莲霜草本修复乳膏 (Bai Lian Shuang Cao Ben Xiu Fu Ru Gao)” was marketed as a “Natural Extract Formula” with “zero steroids” to manage psoriasis, eczema, red and itchy skin. However, when HSA tested the product, it was found to contain a potent steroid (clobetasol), and an antifungal agent (miconazole).

A 12-year-old boy had applied it regularly for two months for his eczema. He rapidly gained 6kg over this period and developed stretch marks on his legs. The child's mother came across the product on Facebook and placed an order with the vendor who was based in Malaysia through Facebook Messenger.

HSA’s investigations found that the overseas vendor’s social media account was linked to a local Shopee store. HSA has since worked with the platform administrator to disable the online store, while the relevant Malaysian authorities have also been alerted to the Facebook account.

See a doctor immediately if you are using “B-LIAN-S HERBAL CREAM". Do not stop using these products suddenly on your own as they contain potent steroids. Sudden discontinuation of steroids (including topical steroids which can be absorbed) may cause severe withdrawal symptoms such as fatigue, weakness and low blood pressure, especially when it has been used for more than a few weeks. Children and infants are more susceptible to the effects of steroids and may be at a higher risk of steroid-associated adverse effects.

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Takeda announced new data from the two pivotal Phase 3 studies of zasocitinib (TAK-279), a next-generation, highly selective and potent oral tyrosine kinase 2 (TYK2) inhibitor, in adults with moderate-to-severe plaque psoriasis (PsO) Presented at the 2026 American Academy of Dermatology (AAD) Innovation Academy, these secondary endpoint data show that zasocitinib demonstrated consistent and high rates of skin clearance across hard-to-treat, high-impact sites, including the scalp, nails, palms and soles, compared with placebo.

These data build on the topline results from the Phase 3 randomized, multicenter, double-blind, placebo- and active comparator-controlled LATITUDE PsO 3001 and 3002 studies. In those studies, about 70% of patients treated with zasocitinib achieved static Physician Global Assessment (sPGA) 0/1 (clear or almost clear skin) at week 16, with a significantly greater Psoriasis Area and Severity Index (PASI) 75 response rate seen as early as week 4 and continuing to increase through week 24. The totality of data shows the potential of zasocitinib to deliver rapid and durable skin clearance — even in the hardest-to-treat areas.

“Psoriasis is a complex, heterogeneous disease that can present differently across patients and over time, particularly in high-impact sites that are often difficult to treat,” said Chinwe Ukomadu, MD, PhD, senior vice president and head, Gastrointestinal & Inflammation Therapeutic Area Unit at Takeda. “TYK2 plays a key role in regulating core disease-driving immune pathways, including the IL-23/IL-17 axis and type I interferon, which contribute to variability in disease presentation and treatment response. Our Phase 3 results reinforce the potential of our next-generation TYK2 inhibitor to deliver rapid, durable and consistent skin clearance in a convenient once-daily pill.”

The 3001 and 3002 studies also evaluated patients who had nail psoriasis, or patients with at least moderate scalp or palmoplantar psoriasis, at baseline.2 Results were consistent across the body, including these difficult-to-treat, high-impact sites:

• Scalp: 77% and 74% of patients with scalp psoriasis treated with zasocitinib achieved scalp-specific PGA (ssPGA) 0/1 response versus placebo (7% and 13%; p<0.001) and apremilast (42% and 30%; p<0.001) at week 16.
  
• Palms and soles (palmoplantar): Approximately 70% of patients with palmoplantar psoriasis treated with zasocitinib achieved numerically higher rates of hands and/or feet-specific PGA (hfPGA) 0/1 response (71% and 69%) versus placebo (22% and 10%) and apremilast (44% and 43%) at week 16.
  
• Nails: Zasocitinib also delivered statistically significant improvements in Nail Psoriasis Severity Index (NAPSI) versus placebo at week 16 (p<0.001).
  
• Responses were sustained through week 24 in both studies.
  
• The most common adverse events through week 24 were upper respiratory tract infection, nasopharyngitis and acne, with no new safety signals identified.
  

Takeda plans to submit a New Drug Application for plaque psoriasis with the United States Food and Drug Administration and other regulatory authorities beginning this fiscal year. Zasocitinib is also being evaluated in Phase 3 studies in psoriatic arthritis

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Background:
Psoriasis is linked to an increased risk of cardiovascular disease, but the impact of psoriasis on cardiac structure and function has been less clear.

Objectives:
To assess cardiac structure, function and cardiometabolic risk factors in individuals with psoriasis compared with matched controls and across psoriasis severity.

Methods:
Cross-sectional analysis of 1010 adults with psoriasis from the prospective PSOCADIA cohort and 1010 age- and sex-matched controls without inflammatory skin disease. Participants underwent clinical assessment and transthoracic echocardiography. Cardiac abnormalities assessed included hypertrophy, valvular disease, systolic and diastolic dysfunction, and myocardial dysfunction defined by global longitudinal strain (GLS) <16%.

Results:
Despite well-managed skin disease, individuals with psoriasis had more prevalent myocardial dysfunction by abnormal GLS (16.7% vs. 6.0%, p < 0.001) compared with controls. This association persisted after adjustment for cardiometabolic risk factors and atherosclerotic cardiovascular disease. Cardiac structure and function were largely similar across psoriasis severity. Higher body mass index and diabetes were independently associated with myocardial dysfunction in psoriasis.

Conclusions:
Individuals with psoriasis, even with well-managed skin disease, exhibit a higher burden of myocardial dysfunction compared with controls, independent of cardiometabolic comorbidity. The prevalence was similar across psoriasis severity, highlighting the importance of cardiovascular assessment in all patients with psoriasis.

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Background:
Psoriasis is a chronic systemic disease with an inflammatory process and systemic involvement that affects the quality of life. Recent research indicates that gut microbiota dysbiosis is common in psoriasis cases, and probiotics have been considered as a potential adjunct therapy; however, the current evidence is limited. The aim of this study was to assess the effects of probiotic supplementation on the severity of psoriasis, treatment satisfaction, and quality of life of patients.

Methods:
Forty-four psoriasis patients between 18 and 70 years old were enrolled in this double-blind, randomized, placebocontrolled trial. They received either topical corticosteroids with a probiotic supplement containing multiple bacterial strains or topical corticosteroids with a placebo for 12 weeks. At the end of the study, changes in the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), along with Treatment Satisfaction Questionnaire for Medication (TSQM), and adverse events were assessed.

Results:
Probiotic supplementation resulted in a greater reduction in PASI scores compared to the control group (46% vs. 15%, p = 0.002). At Week 12, the mean DLQI score was significantly lower in the probiotic group (4.364 ± 5.010) as compared to the control group (8.773 ± 6.015, p < 0.001), with 31.8% of probiotic users reporting no impact on quality of life (DLQI score 0-1) versus 0% in controls. The patient satisfaction with treatment was significantly higher in the probiotic group. No adverse effects were reported.

Conclusion:
Probiotics can be recommended as a safe and effective adjunct therapy for psoriasis. They can enhance clinical outcomes, quality of life, and patient satisfaction. Further, larger trials are needed.

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Psoriasis is a complex chronic inflammatory and autoimmune disease; therefore, reliable and human-relevant animal models are essential for preclinical drug testing and mechanistic studies. SKH-1 mice, which lack functional hair follicles and display a thickened epidermis that more closely resembles human skin than that of C57BL/6 mice, represent a potential psoriasis model, but their suitability remains uncertain.

In this study, proliferation, barrier function, differentiation, and inflammatory responses were assessed in the imiquimod (IMQ)-induced dermatitis model of SKH-1 mice using qRT-PCR, immunofluorescence, and flow cytometry. Transcriptomic profiling via RNA sequencing was performed on total RNA from lesional and non-lesional skin of IMQ-induced SKH-1 mice, IMQ-induced C57BL/6 mice, and human psoriatic skin. A psoriasis-like mouse model was also established in SKH-1 mice to evaluate its utility for recurrence studies.

The results showed that the IMQ-induced SKH-1 mouse model exhibited hyperproliferation, hypodifferentiation, barrier disruption, and excessive inflammatory responses similar to human psoriasis. Transcriptomic analysis further highlighted the advantages and complementarity of this model in studying psoriasis pathogenesis, and the established recurrence model provided a suitable tool for investigating the mechanisms of psoriasis recurrence.

This study compared the transcriptomic signatures of lesional skin between IMQ-induced SKH-1 and C57BL/6 mice and demonstrated that the SKH-1 model can recapitulate vascular dysregulation and disease recurrence, indicating that it serves as a valuable complementary tool for probing psoriasis pathogenesis.