These findings provide reassurance to clinicians and patients and support current recommendations endorsing uninterrupted biologic treatment and routine vaccination for individuals with psoriasis.

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Background:
Biologic therapy in psoriasis raises concerns regarding COVID-19 infection risk and vaccine response, yet real-world data remain limited.

Objective:
To evaluate COVID-19 infection rates, clinical severity, and vaccination response among biologic-treated patients with psoriasis during the COVID-19 pandemic.

Methods:
This cohort study included 12,306 patients with psoriasis followed at a tertiary medical center between March 2020 and May 2023. Primary outcomes included estimated SARS-CoV-2 infection rates, hospitalization, ICU admission, mortality, and a composite severe COVID-19 outcome (hospitalization, ICU admission, or death).

Results:
Based on national seroprevalence-adjusted rates, infection occurred in 673 of 962 biologic-treated patients (70.0%) and 7657 of 11,344 nonbiologic patients (67.5%) (p = 0.18). Hospitalization was more frequent among biologic-treated patients (45.2% vs 25.1%; p < 0.001), while ICU admission rates were comparable (2.6% vs 2.0%; p = 0.41). Mortality was significantly lower in the biologic group (6.3% vs 12.1%; p < 0.001).

Conclusions:
Biologic therapy in psoriasis was not associated with increased susceptibility to SARS-CoV-2 infection or impaired vaccine response.

This study demonstrates that methyltransferase-like 1 (METTL1), an m7G methyltransferase, is significantly upregulated in epidermal keratinocytes of human psoriatic lesions.

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The functional significance of RNA modifications, specifically N7-methylguanosine (m7G), in inflammatory conditions such as psoriasis remains not fully elucidated. This study demonstrates that methyltransferase-like 1 (METTL1), an m7G methyltransferase, is significantly upregulated in epidermal keratinocytes of human psoriatic lesions and imiquimod (IMQ)-induced murine models.

Utilizing mice with an inducible keratinocyte-specific Mettl1 deletion (Mettl1fl/flKrt14-CreERT2), the research reveals significantly attenuated psoriasiform inflammation and decreased neutrophil infiltration relative to Mettl1fl/fl counterparts. Mechanistically, METTL1 drives inflammation by augmenting Bdkrb1 mRNA stability through m7G modification. This stabilization leads to elevated bradykinin receptor B1 (BDKRB1) protein expression, which activates the p38 mitogen-activated protein kinase (MAPK) pathway in keratinocytes, promoting the secretion of key proinflammatory C-X-C motif chemokine ligand (CXCL) chemokines and robust neutrophil chemotaxis. Crucially, both in vivo genetic BDKRB1 overexpression and pharmacological BDKRB1 activation successfully rescue the attenuated inflammatory phenotype in Mettl1-deficient mice, firmly validating this specific signaling cascade.

Conversely, pharmacological inhibition of the METTL1–BDKRB1 axis effectively mitigates psoriasiform inflammation. Collectively, these data establish that METTL1 modulates psoriasis by fostering p38-dependent chemokine production and neutrophil recruitment, identifying the METTL1–BDKRB1 axis as a novel therapeutic target.

A list of medications I have tried…


Pills

Soriatane
Methotrexate
Cyclosporine
Otezla
Sotyktu
Icotrokinra

Biologics

Humira
Cimzia
Enbrel
Stelara
Trymfa
Skyrizi
Ilumya
Cosentyx
Taltz
Silq
Bimzelx

The medications left…

Cyclosporine - I would rather die.
Sotoktu - Low on the priority list.
Icotrokinra - It’s an IL23. No thanks
Ilumya - It’s an IL23. No thanks
Silq - It’s not approved for arthritis. No thanks.
Bimzelx - High on the priority list.

This trial to evaluate Bimzelx (bimekizumab) in Chinese patients with psoriasis, represents the largest clinical trial of bimekizumab conducted in an Asian population to date.

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The BE SHINING study by Cai et al., the phase 3 trial to evaluate bimekizumab in Chinese patients with psoriasis, represents the largest clinical trial of bimekizumab conducted in an Asian population to date. Asian patients with psoriasis have been reported to exhibit distinct pathophysiologic and phenotypic features from those observed in Western populations. This study provides essential validation that the clinical outcomes established in global trials are reproducible within the context of Asian patients.

Indeed, the dual inhibition of IL-17A and IL-17F by bimekizumab yields a profound clinical response in this Chinese cohort. In the present trial, 74.0% of patients achieved PASI 75 as early as week 4, and notably, 94.0% and 65.0% reached PASI 90 and PASI 100, respectively, at week 16. Overall, these findings confirm that the high-level efficacy of bimekizumab established in global clinical trials is consistently maintained in this regional setting.

Regarding safety, bimekizumab demonstrated a tolerable safety profile in the BE SHINING study, with no new safety signals identified. Consistent with global clinical trials, upper respiratory tract infections were the most common treatment-emergent adverse events (TEAEs). Interestingly, no cases of oral candidiasis were reported, similar to findings from a Korean study, but contrasting with data from global and Japanese populations where oral candidiasis was a relatively common TEAE. As the authors suggested, a small sample size or a short observation period may partially explain this discrepancy. However, the comparable size (n = 133) to the Japanese cohort (n = 108) and the typical early onset of candidiasis during the first 16 weeks of treatment in global trials suggest that population-specific factors, such as characteristic oral microbiomes or distinct immunologic profiles, may play an important role. These findings highlight the need for real-world data on bimekizumab in Asian populations and further mechanistic studies to clarify the factors driving this phenomenon.

Another notable safety finding was the higher frequency of hepatic events compared with global clinical trials. Given that the rate of hepatic events was similar between the bimekizumab and placebo groups and considering the pharmacologic profile of IL-17 inhibitors, these events are unlikely to be directly related to the drug. Instead, they may reflect the high baseline prevalence of hepatic disorders (21.1%) in this population, which the authors suggest is likely associated with metabolic dysfunction–associated steatotic liver disease (MASLD). Clinicians may nevertheless consider monitoring liver function in patients with psoriasis at high risk of hepatic events (i.e. underlying MASLD, obesity or excessive alcohol consumption) while receiving bimekizumab when clinically indicated, not to detect drug-related hepatotoxicity but to assess underlying liver disease. Patients should also be encouraged to adopt lifestyle modifications, even when psoriasis is well controlled with bimekizumab.

In summary, this study reaffirms that bimekizumab delivers a rapid and profound clinical response, including high rates of PASI 90 and PASI 100 in Chinese patients with psoriasis, consistent with previous global trials. Although distinct patterns in the rates of oral candidiasis and hepatic events were observed in this regional cohort, these findings do not alter the overall favourable benefit–risk profile of bimekizumab. Further real-world studies are warranted to confirm these observations and to clarify the population-specific factors that may influence clinical outcomes in Asian patients.

Uncovering why inflammatory bowel disease patients face higher psoriasis risks and the role of epidermal growth factor receptor, body mass index and air quality.

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Background and Aim:
Psoriasis and inflammatory bowel disease are characterized by relapsing episodes of immune-mediated, chronic inflammation and frequently co-occur. However, the potential causal relationship between these two conditions and their shared pathogenesis remains unclear. We aimed to explore the pathogenesis and association between psoriasis and inflammatory bowel disease.

Methods:
We performed longitudinal cohort analyses using the UK Biobank and additionally incorporated three independent external datasets—the International IBD Genetics Consortium GWAS dataset, the FinnGen psoriasis GWAS dataset, and the plasma proteome dataset reported by Sun et al. to conduct Mendelian randomization and proteomic mediation analyses, thereby investigating the association between inflammatory bowel disease and psoriasis and exploring potential underlying mechanisms.

Results:
Inflammatory bowel disease increased psoriasis risk in the UK Biobank cohort, as indicated by the Cox model and Mendelian randomization analysis. Smoking, body mass index, and air pollution were identified as risk factors for psoriasis in inflammatory bowel disease patients. In addition, multiple intermediary proteins and their activation pathways were implicated. The epidermal growth factor receptor substrate 15-like 1 was demonstrated as a mediating protein for Crohn's disease and ulcerative colitis in the incidence of psoriasis. Enrichment analysis indicated that the downregulation and signaling of the epidermal growth factor receptor were potential biological mechanisms contributing to the causal relationships between genetic effects and the development of psoriasis and inflammatory bowel disease.

Conclusion:
The epidermal growth factor receptor pathway is a potential mechanism in inflammatory bowel disease-induced psoriasis. This study may inform the clinical management of psoriasis and inflammatory bowel disease.

Icotyde (icotrokinra) demonstrated high rates of overall skin, scalp, genital and hand/foot psoriasis clearance, and improvements in nail psoriasis, through 1 year.

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Background:
High-impact site plaque psoriasis is difficult to treat. Icotrokinra, an oral peptide with high specificity for the interleukin (IL)-23 receptor, demonstrated significantly higher rates of high-impact site psoriasis clearance, versus placebo, with no safety signals, through Week (W)16.

Objectives:
Report clinical response rates and safety through 1 year of icotrokinra treatment in participants with high-impact site plaque psoriasis.

Methods:
Participants (≥12 years of age; psoriasis body surface area ≥1%; Investigator's Global Assessment [IGA] ≥2) with at least moderate scalp, genital or hand/foot psoriasis were randomized (2:1) to once-daily icotrokinra 200 mg (N = 208) or placebo (N = 103), with placebo-to-icotrokinra transition at W16 (N = 92). Rates (using nonresponder imputation) of achieving clear/almost clear (0/1) or clear (0) overall skin (IGA), genital (static Physician's Global Assessment of genitalia [sPGA-G]), hand/foot (hf-PGA) psoriasis and absent/very mild (0/1) or absent (0) scalp psoriasis (scalp-specific-IGA [ss-IGA]), modified Nail Psoriasis Severity Index (mNAPSI) percent improvement and safety were assessed through W52.

Results:
Eighty-eight per cent (275/311) of participants completed treatment through W52. In icotrokinra-randomized participants, response rates increased through W24 and were durable through W52 for overall psoriasis clearance (IGA 0/1 range: 67%–70%) and across high-impact sites (ss-IGA 0/1: 72%–78%; sPGA-G 0/1: 85%–90%; hf-PGA 0/1: 54%–62%); responses were consistent among placebo-randomized participants after transitioning to icotrokinra. High proportions of icotrokinra-randomized participants achieved complete clearance during W24–52 (IGA 0: 44%–51%; ss-IGA 0: 57%–66%; sPGA-G 0: 73%–84%; hf-PGA 0: 44%–58%). Mean mNAPSI improvement increased from W16 (33%) to W52 (62%). Exposure-adjusted rates of participants with ≥1 adverse event (AE) or serious AE through W16 were similar between icotrokinra and placebo, with no increase in AE rates or occurrence of a safety signal through W52.

Conclusions:
Icotrokinra demonstrated high and durable rates of psoriasis clearance across high-impact sites, with a favourable safety profile, through 1 year.

Initial study reports distinct improvement from "Ozone Sauna & Ozonated Olive Oil" in the treatment of psoriasis with minimal risk.

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Psoriasis is an immune-mediated skin disease in which genetic and environmental factors have a significant role. Olive oil with antioxidant properties is an effective adjunct treatment for skin diseases. Furthermore, ozone by introducing O2 into the bloodstream controls the response of cell-mediated immunity and leads to improve disease. So, the aim of this study was to evaluate the efficacy of ozone therapy in the treatment of Psoriasis.

Topical therapy of lesions of a man suffering from psoriasis was carried out using ozonate olive oil two times a day and ozone sauna once a week during a month. Patient showed considerable improvement after about twenty days.

As the itching and silvery-white scaling decreased, the lesions began to resolve after three weeks. Furthermore, no recurrence was noted after 3 months of follow-up.

It is suggested that ozone therapy, in appropriate formulations and in controlled cases, has a role in the treatment of patients with psoriasis by inhibiting the inflammatory pathways and prompting regenerative characteristics, without significant adverse effects and the necessity for systemic pharmacological agents. So, more studies on a greater population are needed to confirm this finding.

This review suggests macrophages might be the key to unlocking better psoriasis treatments.

"Macrophages are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that are specific to healthy body cells on their surface"

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This review provides a comprehensive overview of macrophage heterogeneity, polarisation dynamics, metabolic reprogramming and multicellular interactions of macrophages in psoriasis.

We discuss how single-cell technologies have revealed diverse macrophage subsets and explore the metabolic profile of macrophages in psoriasis. Furthermore, we examine the central role of macrophages in intercellular networks with keratinocytes, T helper 17 (Th17) cells, neutrophils, fibroblasts and sensory neurons.

Additionally, we summarise the novel signal way of macrophages and tissue injury by macrophages. Finally, we summarise emerging therapeutic strategies—including metabolic modulators, signalling pathway inhibitors, advanced delivery systems and cell-based therapies.

By integrating recent insights from single-cell omics, spatial transcriptomics and metabolic studies, this review underscores the potential of macrophage-focused interventions for psoriasis treatment.

My PsA has added Plantar Fasciitis to it's never ending array of gifts. It's really a bit of body wack-a-mole. Fix one thing, and another will crop up. Anyway my Dr recommends Crocs, but they're very expensive here, and not really practical for our wet winters. Anyone have any experience with this and perhaps have other recommendations?

Does your lifestyle affect your psoriatic arthritis (PsA) ? this study looked at the latest research.

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Objective:
This study aims to investigate lifestyle-related factors in patients with psoriatic arthritis (PsA) and their association with disease activity measurements.

Methods:
This multicenter cohort included 938 patients newly diagnosed with PsA, between 2013 and 2023. A composite lifestyle risk score (range 0 to 5) was calculated using five lifestyle-related factors assessed at baseline (BMI outside normal range, abdominal obesity, current smoking, no alcohol consumption, physical inactivity). Higher scores indicate the presence of more lifestyle-related risk factors. One year disease activity outcomes included PsA Disease Activity Score (PASDAS), disease activity in PsA (DAPSA), PASDAS and DAPSA low disease activity (LDA) and remission, and minimal disease activity (MDA).

Results:
The rate of obesity was 33%, abdominal obesity was 51%, current smoking was 19%, and alcohol consumption was 72% with 3% of patients physically inactive. Using multivariable analyses, a higher lifestyle risk score was associated with higher PASDAS (β 0.15; 95%CI 0.08, 0.23), and lower odds for achieving PASDAS-LDA (OR 0.59; 95%CI 0.45, 0.77), and MDA (OR 0.72; 95%CI 0.57, 0.90) at one year follow-up. Similar associations were observed for DAPSA (βadj 1.18; 95%CI 0.65, 1.71) and DAPSA-LDA (OR 0.74; 95%CI 0.59, 0.92). Analysis of individual factors showed that general obesity, abdominal obesity and smoking, were significantly associated with higher PASDAS and DAPSA, and lower odds for achieving PASDAS-LDA and MDA.

Conclusion:
Lifestyle-related risk factors were prevalent in patients with PsA. The associations between lifestyle-related factors and PsA disease activity, mainly obesity and smoking, provide foundation to address lifestyle in PsA care.

A Korean nationwide cohort study looking at particulate matter (PM) and onset and exacerbation of psoriasis.

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Psoriasis is a chronic inflammatory skin disease influenced by environmental factors, including air pollution. However, large-scale evidence from Asian populations, where particulate matter (PM) exposure is relatively high, remains limited.

This study aimed to evaluate the association between long-term PM exposure and psoriasis incidence, and short-term exposure with exacerbation risk. We conducted a cohort study using the Korean National Health Insurance Service database, involving 8 396 764 individuals.

Long-term exposure was assessed based on annual average concentrations of fine PM (PM2.5) and coarse PM (PM10), while short-term exposure was measured using daily PM levels matched with control days. Long-term exposure to PM2.5 and PM10 was associated with a 19% and 27% higher risk of incident psoriasis (adjusted HR 1.19 and 1.27; 95% CI 1.16–1.22 and 1.25–1.30). Short-term exposure was linked to an increased risk of psoriasis exacerbation (adjusted OR 1.03 for PM2.5, 95% CI 1.00–1.06; adjusted OR 1.01 for PM10, 95% CI 1.00–1.03).

Stronger associations were observed in younger individuals, urban residents, those with lower socioeconomic status, ever-smokers, and patients with comorbid allergic diseases.

These findings suggest that both long-term and short-term PM exposure contribute to psoriasis onset and exacerbation, underscoring air pollution as an important modifiable risk factor in psoriasis development and control.

Vanda Pharmaceuticals publish efficacy and safety results of Imsidolimab for generalised pustular psoriasis (GPP)

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Background:
Generalized pustular psoriasis (GPP) is a rare, life-threatening disease attributed to aberrant interleukin-36 (IL-36) activity, often due to variants in the IL-36 receptor antagonist gene. Imsidolimab is a novel, humanized, affinity-matured immunoglobulin G4 monoclonal antibody that binds the IL-36 receptor and antagonizes IL-36 signaling.

Methods:
Two phase 3 trials were conducted at 26 clinical sites within 11 countries investigating imsidolimab treatment for GPP. GEMINI-1 was a double-blind, placebo-controlled trial that randomly assigned 45 patients (18–80 years of age) with a GPP flare to receive either a single intravenous dose of 300 mg of imsidolimab, 750 mg of imsidolimab, or placebo. The primary endpoint was GPP Physician Global Assessment (GPPPGA) scores of clear (0) or almost clear (1) at week 4 (range: 0 [clear] to 4 [severe]; minimally clinically important difference, 1.4). GEMINI-2 was a follow-on relapse prevention trial with a primary objective of evaluating the safety of imsidolimab up to 104 weeks. Patients who improved with treatment in GEMINI-1 were randomly assigned to receive either 200 mg of subcutaneous imsidolimab or placebo monthly, whereas partial responders received open-label 200 mg of subcutaneous imsidolimab monthly.

Results:
In GEMINI-1, 53% of patients in the groups that received either 300 mg (n=8/15) or 750 mg (n=8/15) of imsidolimab had GPPPGA scores of 0 or 1 at week 4, compared to 13% in the placebo group (n=2/15) (P=0.023 for both the 300 mg vs. placebo comparison and 750 mg vs. placebo comparison). In GEMINI-2, no serious adverse events led to imsidolimab discontinuation.

Conclusions:
Compared with placebo, a significantly higher proportion of patients with GPP randomly assigned to receive a single intravenous dose of imsidolimab were clear or almost clear of the disease after 4 weeks based on the GPPPGA. There were no serious adverse events that led to treatment discontinuation with imsidolimab up to 104 weeks of treatment.

Could psoriasis flares be linked to cellular energy and mitochondria?

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Background:
Psoriasis is an immune-mediated inflammatory disease driven by dysregulated crosstalk between immune cells and skin-resident cell populations, particularly keratinocytes and fibroblasts. However, transcriptomic findings across studies remain heterogeneous and incompletely integrated.

Objectives:
To integrate transcriptomic evidence across independent studies to define reproducible immune-gene expression patterns in plaque psoriasis and identify hypothesis-generating pathways beyond canonical immune programmes.

Methods:
We performed a systematic review and meta-analysis of transcriptomic datasets comparing lesional psoriatic skin with non-lesional skin and healthy controls. All analyses were restricted a priori to a curated set of immune-related genes. Forty-four independent studies comprising 975 samples were harmonized; differential expression within each study was combined using random-effects models. Functional enrichment (Reactome/KEGG/GO) and a systematic comparison with curated resources were conducted.

Results:
The meta-analysis identified 1780 immune-related genes consistently dysregulated in lesional psoriasis. Enrichment confirmed established immune programmes (e.g. IL-23/Th17 signalling, cytokine-mediated responses and type I interferon pathways). When cross-referenced with curated disease–gene resources, 1119 genes overlapped with previously reported psoriasis-associated genes, whereas 661 genes were not systematically highlighted. Exploratory enrichment among the less-characterized genes suggested additional processes involving glucose metabolism (gluconeogenesis), FoxO signalling and mitophagy, each supported by small gene sets and borderline adjusted p-values, and therefore interpreted as hypothesis-generating rather than definitive.

Conclusions:
By integrating 44 datasets under an explicit immune-gene framework, this study refines consensus immune signatures in psoriasis and prioritizes metabolic and mitochondrial processes as testable hypotheses for future functional work. These findings contextualize expected immune activation and point to potential interfaces between immunity, cellular energetics and mitochondrial quality control in lesional skin.

Kyntheum / Siliq (brodalumab) in patients with palmoplantar pustulosis psoriasis (PPP) demonstrated a long-term benefit not only to skin but also improved dermatology life quality index (DLQI)

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Background:
The efficacy and safety of brodalumab in Japanese patients with palmoplantar pustulosis (PPP) were demonstrated during the 16-week double-blind phase of a randomized controlled trial. However, long-term data are unavailable.

Objectives:
To assess the efficacy and safety of brodalumab 210 mg administered subcutaneously (SC) repeatedly until Week 68 in PPP patients with moderate or severe pustules/vesicles in an open-label extension study.

Methods:
In a multicentre, Phase 3, randomized, double-blind, placebo-controlled trial, Japanese adults having a diagnosis of PPP for ≥24 weeks, PPP Area Severity Index (PPPASI) of ≥12, PPPASI subscore of pustules/vesicles of ≥2 and inadequate response to therapy were included. Patients completing the double-blind phase with brodalumab 210 mg or placebo  SC once every 2 weeks (Q2W) for 16 weeks were invited to enter the open-label extension to receive brodalumab for the subsequent 52 weeks.

Results:
By Week 68, 35 patients in the brodalumab group and 43 patients in the placebo-to-brodalumab group completed the study, with discontinuations (28 and 20 patients, respectively) primarily due to patient withdrawal. At Week 68, the mean ± SD improvement of the PPPASI total score from baseline was 23.83 ± 12.28 and 22.37 ± 13.09 in the brodalumab and placebo-to-brodalumab groups, respectively. Continued improvement or trend for improvement was seen in the secondary endpoints such as PPPASI 50/75/90 responses and Dermatology Life Quality Index. The incidence of adverse events was 849.3/100 person-years. Otitis externa had the highest incidence (44.0/100 person-years; Grade 1 or 2 only). Infection-related events were frequent but controllable.

Conclusions:
Brodalumab SC 210 mg Q2W administered for 68 weeks showed a long-term benefit to both dermatological and quality of life indices in these patients. It is expected to be used in appropriate patients, considering both safety risks and efficacy benefits.

Is it time to rethink using bio treatments earlier for psoriatic arthritis (PsA) ?

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A major strength of the study lies in its thoughtful design, which addresses two key sources of bias that have affected previous analyses: protopathic bias and confounding-by-indication. By excluding PsA cases diagnosed within 1 year of biologic initiation, the authors reduce the likelihood that early, subclinical joint symptoms prompted the switch to biologics. Similarly, by restricting the baseline population to patients who had all received phototherapy—used here as a proxy for moderate-to-severe psoriasis—the study ensures a more comparable starting point between cohorts. This is a notable improvement over earlier claim-based studies that compared biologic users with patients treated only with topicals or mild systemic agents, inadvertently mixing populations with very different baseline risks.

The results are compelling: The fully adjusted hazard ratio for PsA development among biologic users was 0.66, indicating a 34% relative risk reduction. This effect persisted across multiple sensitivity analyses, including age-, sex- and ethnicity-matched cohorts. Although observational data cannot establish causality, the consistency of the findings strengthens the argument that biologics may modify the natural history of psoriatic disease.

Biologically, this hypothesis is plausible. Psoriasis and PsA share overlapping immunopathogenic pathways, particularly involving TNF-α, IL-17 and IL-23. Subclinical entheseal inflammation is well-documented in psoriasis patients, even in the absence of joint symptoms. Early suppression of these inflammatory pathways may theoretically prevent progression to clinical PsA. Indeed, imaging studies have shown that biologics can reduce enthesitis and synovitis detectable by ultrasound or MRI, even in patients without established PsA.

However, several limitations warrant consideration. First, the use of phototherapy as a surrogate for disease severity, while pragmatic, is imperfect; treatment selection is influenced by patient preference, access and physician practice patterns. Second, claims databases lack granular clinical data such as PASI scores, body surface area, nail involvement or family history—factors known to influence PsA risk. Third, although PsA diagnoses were restricted to rheumatologists, misclassification remains possible. Finally, the study does not differentiate between biologic classes; whether IL-23 inhibitors, IL-17 inhibitors, or TNF inhibitors differ in their preventive potential remains debatable.

Despite these limitations, the study adds weight to a growing body of evidence suggesting that early systemic intervention may alter the trajectory of psoriatic disease. If confirmed in prospective studies, this could have meaningful implications for clinical practice. Dermatologists may increasingly consider early biologic therapy not only to control skin inflammation but also to reduce the long-term burden of PsA, a condition associated with irreversible joint damage, disability and reduced quality of life.

Future research should focus on prospective cohorts with standardized clinical assessments, imaging biomarkers and stratification by biologic class. Randomized controlled trials designed specifically to evaluate PsA prevention—although challenging—would provide the highest level of evidence. Until then, the findings by Miao et al. represent an important step towards understanding how timely intervention may reshape the natural history of psoriatic disease.

This Japanese study evaluated the treatment outcomes of stubborn (refractory) regions of psoriasis and psoriatic arthritis treated with biologics.

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Systemic therapies are required to control disease severity of patients with psoriasis vulgaris (PsO) and psoriatic arthritis (PsA) experiencing refractory skin lesions that persisted despite systemic therapies.

Various oral medications and biologics are currently available in Japan. The aim of this study was to evaluate the treatment outcomes of refractory regions of PsO and PsA treated with systemic therapy. A total of 77 patients who received oral medications and biologics between 1 January 2010 and 31 March 2019 at the Jichi Medical University Hospital were enrolled.

The PsO group included 39 men and 11 women, whereas the PsA group included 20 men and 7 women. Oral medications included etretinate (7 PsO patients and 3 PsA patients), cyclosporine (39 PsO patients and 20 PsA patients), apremilast (7 PsO patients), and methotrexate (5 PsA patients), including 4 patients treated with etretinate and cyclosporine combination (3 PsO patients and 1 PsA patient). The biologics included infliximab (5 PsO patients and 8 PsA patients), adalimumab (11 PsO patients and 11 PsA patients), ustekinumab (21 PsO patients and 6 PsA patients), guselkumab (5 PsO patients), secukinumab (2 PsO patients and 1 PsA patient), ixekizumab (5 PsO patients and 1 PsA patient), and brodalumab (1 PsO patient).

The most common biologic-resistant regions were the lower extremities, followed by the upper extremities and back in patients with PsO, and the scalp, followed by the lower extremities and abdomen in patients with PsA. Despite the introduction of biologics, no significant differences were observed in the efficacy on the face, neck, palm, and buttocks in patients with PsO and the face, sole, and buttocks in patients with PsA compared to oral medications.

These findings will provide useful information regarding biologic-resistant psoriatic regions in the Japanese patients.

Unravelling the psoriasis and cardiovascular–kidney–metabolic (CKM) health link and its impact on life expectancy.

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Background:
Limited evidence exists concerning the relationship between cardiovascular–kidney–metabolic (CKM) health and the incidence and prognosis of psoriasis.

Objectives:
This study aimed to evaluate the associations between CKM status, genetic risk and the risk of developing psoriasis, as well as to examine the impact of CKM syndrome on life expectancy in patients with psoriasis.

Method:
This prospective cohort study included 392,454 participants free of psoriasis from the UK Biobank. CKM syndrome was defined by the presence of metabolic risk factors, chronic kidney disease and cardiovascular disease, categorized into five stages (0–4). The genetic risk of psoriasis was assessed using a polygenic risk score. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the incident risk of psoriasis.

Results:
Compared to participants in stage 0, the multivariable-adjusted HRs (95% CIs) for developing psoriasis in individuals with CKM stages 1, 2, 3 and 4 were 1.21 (1.06–1.38), 1.38 (1.24–1.55), 1.64 (1.42–1.91) and 1.72 (1.47–2.01), respectively. Joint association analyses revealed that participants with CKM stage 4 and high genetic risk had the highest risk of psoriasis compared to those at stage 0 with low genetic risk (HR = 2.82, 95% CI: 2.28–3.49). Notably, there was a significant positive additive interaction between advanced CKM stages and high genetic risk in the development of psoriasis (RERI = 0.82, 95% CI: 0.35–1.32). Additionally, within the psoriasis population, advanced CKM stage (stage 4) was associated with a greater reduction in life expectancy (2.03 years, 95% CI: 0.25–3.81 years).

Conclusions:
Poor CKM health was significantly associated with a higher risk of psoriasis in midlife and older adults, particularly among those with high genetic risk and was further linked to decreased life expectancy among patients with psoriasis.

This study investigated the role of proliferation-associated protein 2G4 (PA2G4) as a possible target for treating psoriasis.

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Proliferation-associated protein 2G4 (PA2G4) has been identified as a key driver of keratinocyte overgrowth and survival in psoriasis, highlighting a promising new target for treatment.

Psoriasis, a chronic inflammatory skin condition affecting approximately 2–3% of the global population, is characterised by excessive keratinocyte proliferation and impaired differentiation. While current therapies have improved disease management, a subset of patients experience inadequate response or loss of efficacy over time, underscoring the need for novel therapeutic strategies.

Study Highlights PA2G4 Role in Psoriasis Progression:
In this study, researchers investigated the role of PA2G4, a transcription factor previously studied primarily in cancer biology, where it is known to promote cell growth and inhibit apoptosis. Using a combination of bulk, single-cell, and spatial RNA sequencing alongside immunohistochemistry, the researchers found that PA2G4 expression was significantly elevated in psoriatic skin compared with non-lesional controls. Notably, its expression was largely confined to basal keratinocytes, the primary proliferating cells in the epidermis.

Importantly, PA2G4 levels were positively correlated with disease severity, epidermal thickening (acanthosis), neutrophil infiltration, and the expression of genes associated with psoriasis pathology. These findings suggest a central role for PA2G4 in driving disease activity.

Functional experiments provided further insight. Using CRISPR/Cas9-mediated knockout of PA2G4 in primary human keratinocytes, researchers observed a shift from proliferation towards differentiation. This was accompanied by reduced expression of proliferation- and inflammation-related genes, including MKI67, IL20, VEGFA, and HIF1A, alongside increased expression of differentiation markers.

In laboratory models, loss of PA2G4 reduced keratinocyte proliferation, limited inflammation-induced epidermal thickening, and increased cell death. Similarly, pharmacological inhibition using the small molecule WS6 replicated these effects, suppressing pathways linked to cell growth and survival.

Clinical Potential of PA2G4 Targeting in Psoriasis:
Together, these findings position PA2G4 as a critical regulator of epidermal homeostasis in psoriasis. Targeting this protein could offer a novel therapeutic approach aimed at restoring the balance between keratinocyte proliferation and differentiation.

Further research is needed to validate these findings in clinical settings, but the study provides a strong foundation for the development of PA2G4-targeted therapies in psoriasis.

Melinda (Mel) here. I stumbled on this resource as I was digging into the rabbit hole of Low Dose Naltrexone. I just started taking 0.5 mg 3 days ago for multiple reasons, scalp psoriasis being a big one. I also have an area on my scapula that is so so itchy and I am pretty sure it guttate. It also has paresthesia, like pins and needles under the skin in that area. My derm recommended Otezla but I am concerned about side effects with that. I am pleased that some of the limited studies show even a little hope that LDN can work. We shall see. Also, planning on a sober summer and giving up my evening IPA is no small sacrifice. ?  So glad this forum is available and I look forward to learning more.