Exploring the role and mechanism of lysophosphatidylcholine (LPC) on the pathogenesis of psoriasis.

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Background:
Although abnormal metabolism plays a critical role in the pathogenesis of psoriasis, the details are unclear.

Objectives:
Here, we identified to explore the role and mechanism of lysophosphatidylcholine (LPC) on the pathogenesis of psoriasis.

Methods:
The level of LPC in plasma and skin lesions and the expression of G2A on skin lesions of psoriasis patients were detected by enzyme-linked immunosorbent assay, liquid chromatography-tandem mass spectrometry, or immunohistochemistry, respectively. The glycolysis in the skin lesions of imiquimod (IMQ)-induced psoriasis-like mouse model was detected by extracellular acidification rate. LPC was subcutaneously injected into IMQ-treated mouse ears, and the phenotype as well as the glycolysis were evaluated. Exploring the effects and mechanism of LPC on keratinocytes and CD4+ T cells by culturing primary keratinocytes and CD4+ T in vitro.

Results:
We found that LPC was significantly increased both in the plasma and skin lesions of psoriatic patients, while G2A, exerting an essential role in LPC inducing biological functions, was increased in psoriatic lesions. The abundance of LPC was positively correlated with glycolytic activity in the psoriasis-like mouse model. LPC treatment facilitated psoriasis-like inflammation and glycolytic activity in skin lesions. Mechanistically, the LPC/G2A axis significantly triggered glycolytic activity and produced inflammatory factors in keratinocytes, and blockade of glycolysis abrogated LPC-induced expression of inflammatory mediators in keratinocytes. LPC activated STAT1, resulting in recognition and binding to the promoters of GCK and PKLR, which are glycolytic rate-limiting enzymes. Furthermore, the LPC/G2A axis directly benefited Th1 differentiation, which was dependent on LPC-induced glycolytic activity. Notably, LPC indirectly facilitated Th17 differentiation by inducing the secretion of IL-1β in keratinocytes-T cells coculture system.

Conclusions:
Taken together, our findings revealed the role of the LPC/G2A axis in the pathogenesis of psoriasis; targeting LPC/G2A is a potential strategy for psoriasis therapy.

Does anyone getting jabs delivered in the uk know what the deal is with these firms?

As far as I can see they are two separate firms (sciensus used to be healthcare at home)
But they both contact me to try and arrange my delivery - one you can do online, the other wants you to use an app.

I’ve arranged this delivery with one of the firms, but was curious so I asked my derm nurse whether two different firms were both trying to deliver my jabs.

They answered by telling me the firm I was set up to get my jabs from - without answering my question about who the other guys are - anyone know anything more cos I think it’s weird.

This study evaluated the risk of first occurrence and recurrence of uveitis in patients with psoriasis in the Korean population.

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Background:
Evidence for the association between psoriasis and uveitis according to the severity of psoriasis including psoriatic arthritis (PsA) and type of uveitis is lacking, and there are no data on the frequency or timing of recurrence of uveitis in patients with psoriasis.

Objectives:
We aimed to evaluate the risk of first-occurrence and recurrence of uveitis in patients with psoriasis in the Korean population. We further evaluated the risk of uveitis according to the severity of psoriasis, comorbidity of PsA, and location of uveitis.

Methods:
In a nationwide retrospective cohort study, we compared 317,940 adult patients who had psoriasis with 635,880 matched controls. Incidence rates (IRs) and estimated IR ratios of the first occurrence and recurrence of uveitis were calculated using survival analysis and Poisson regression, respectively.

Results:
The rate of uveitis incidence and uveitis recurrence in patients with psoriasis were 1.18 and 2.31 per 1,000 person-years, respectively. Compared with the controls, the IR ratios of development and recurrence of uveitis in patients with psoriasis were 1.14 (95% CI 1.08, 1.2) and 1.16 (95% CI 1.12, 1.21), respectively. The recurrence rate of uveitis was highest within 3 years after the onset of psoriasis. The corresponding IR ratios for uveitis recurrence in patients with mild psoriasis, severe psoriasis, and PsA were 1.11 (1.06, 1.16), 1.24 (1.16, 1.33), and 1.49 (1.31, 1.7), respectively. Patients with psoriasis had an increased risk of recurrence of anterior uveitis, and patients with both psoriasis and PsA had an increased risk of recurrence of both anterior and pan-uveitis.

Conclusions:
Patients with psoriasis had a higher risk of both development and recurrence of uveitis, especially with severe psoriasis and PsA. The timing of uveitis recurrence was related to the onset of psoriasis, and patients who had psoriasis with PsA had an increased risk of vision-threatening pan-uveitis.

Understand the connection between psoriasis and cardiovascular disease.

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Background:
Psoriasis is an inflammatory skin disease associated with increased cardiovascular (CV) risk, whose pathogenesis is not fully known.

Objective:
We identified a transcriptomic signature in psoriasis and investigated its association with prevalent and future risk of a CV event to understand the connection between psoriasis and CV disease (CVD).

Methods:
Psoriasis patients (n=37) with a history of moderate-severe skin disease without CVD and 11 matched controls underwent whole blood RNA sequencing. This transcriptomic signature in psoriasis vs controls was evaluated in two CVD cohorts: Women referred for cardiac catheterization with (n=76) vs without (n=97) myocardial infarction (MI), and patients with peripheral artery disease (n=106) followed over 2.5 years for major adverse CV or limb events (MACLE). The association between genes differentially expressed in psoriasis and prevalent and incident CV events was assed.

Results:
In psoriasis, median age was 44 (IQR; 34 – 51) years, 49% male, and ACC/AHA ASCVD Risk Score of 1.0% (0.6 – 3.4) with no significant difference vs controls. The median psoriasis area and severity index score (PASI) was 4.0 (IQR 2.9 – 8.2) with 36% on biologic therapy. Overall, 247 whole blood genes were upregulated and 228 downregulated in psoriasis vs controls (p<0.05), and 1,302 genes positively and 1,244 genes negatively correlated with PASI (p<0.05). Seventy-three genes overlapped between psoriasis prevalence and PASI with key regulators identified as IL-6, IL-1β, and interferon gamma. In the CVD cohorts, 50 of 73 genes (68%) identified in psoriasis associated with prevalent MI, and 29 (40%) with incident MACLE. Key regulator transcripts identified in psoriasis and CVD cohorts included SOCS3, BCL3, OSM, PIM2, PIM3, and STAT5A.

Conclusions:
A whole blood transcriptomic signature of psoriasis diagnosis and severity associated with prevalent MI and incident MACLE. These data have implications for better understanding the link between psoriasis, systemic inflammation, and CVD.

This study looked at the effect of biologic therapy in HIV patients with psoriasis.

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Background:
Psoriasis is a chronic immune mediated inflammatory disorder which also occurs in the setting of HIV. Biologic therapy has transformed the treatment landscape for psoriasis however individuals with HIV are excluded from clinical trials. The impact of biologic therapy upon blood parameters in HIV is unclear and only observed in small case series.

Objective:
To assess the effect of biologic therapy in psoriasis vulgaris in individuals with well controlled HIV, upon CD4+ cell counts, CD4+ proportion and HIV Viral load over 12 months.

Methods:
This retrospective cohort study was conducted at a tertiary referral centre in Sydney, Australia and included 36 HIV-positive individuals with psoriasis treated with biologic therapy, compared to 144 age, gender and HAART-matched individuals without psoriasis seen between 2010-2022. Outcomes of interest included HIV Viral Load, CD4+ cell count and incidence of infections.

Results:
No statistically significant difference was seen in baseline HIV Viral load and CD4+ count between individuals with psoriasis and without psoriasis. No significant change in CD4+ count or HIV Viral load was seen over the 12-month period of analysis in the HIV cohort without psoriasis. The HIV cohort treated with biologic therapy for psoriasis also did not demonstrate any significant change in HIV Viral load and CD4+ counts over the 12-month period examined. Stratification by type of biologic therapy used did not identify any significant changes in these parameters. Rates of infections and adverse events were also not significantly different between cohorts. It is possible that minor blips seen in the biologics cohort may be a risk factor for future virological failure, and future prospective longitudinal studies are required.

Conclusions:
In individuals with well controlled HIV, the use of biologic therapy for psoriasis does not significantly impact HIV Viral load, CD4+ cell count, CD4+ proportion and rates of infection over the first 12 months of therapy.

Hi all, it's been a while since I last posted. I thought I'd give an update on things.

After over a year on skillerence with no real results but plenty of stomach cramps, and with my immune system dropping to 0.6 my derm has decided that I should move onto Humira.

Now, for full disclosure I thought I'd inform you that I suffer from terrible health anxiety and this isn't helped by reading the possible side effects which sound terrifying, with everything from TB to lymphoma.

This has been enough to make me think that maybe psoriasis may not be that bad after all.

If I do start Humira, what are the odds of any of the effects actually happening? I need to process this in order to move forward with treatment otherwise I think I'll not try anything again.

Thanks in advance.

This study looked at the mortality trends of Psoriasis (PsO) and Psoriatic arthritis (PsA) between 2010 and 2021, focusing on the effects of the COVID-19 pandemic.

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Background:
Little is known about mortality trends among patients with psoriasis (PsO) and psoriatic arthritis (PsA) in the United States.

Objectives:
To ascertain mortality trends of PsO and PsA between 2010 and 2021, focusing on the effects of the COVID-19 pandemic.

Methods:
We collected data from the National Vital Statistic System and calculated age-standardized mortality rates (ASMR) and cause-specific mortality for PsO/PsA. We evaluated observed versus predicted mortality for 2020–2021 based on trends from 2010 to 2019 with joinpoint and prediction modelling analysis.

Results:
Among 5810 and 2150 PsO- and PsA-related deaths between 2010 and 2021, ASMR for PsO dramatically increased between 2010–2019 and 2020–2021 (annual percentage change [APC] 2.07% vs. 15.26%; p < 0.01), leading to a higher observed ASMR (per 100,000 persons) than predicted for 2020 (0.27 vs. 0.22) and 2021 (0.31 vs. 0.23). The excess mortality of PsO was 22.7% and 34.8% higher than that in the general population in 2020 (16.4%, 95% CI: 14.9%–17.9%) and 2021 (19.8%, 95% CI: 18.0%–21.6%) respectively. Notably, the ASMR rise for PsO was most pronounced in the female (APC: 26.86% vs. 12.19% in males) and the middle-aged group (APC: 17.67% vs. 12.47% in the old-age group). ASMR, APC and excess mortality for PsA were similar to PsO. SARS-CoV-2 infection contributed to more than 60% of the excess mortality for PsO and PsA.

Conclusions:
Individuals living with PsO and PsA were disproportionately affected during the COVID-19 pandemic. Both ASMRs increased at an alarming rate, with the most pronounced disparities among the female and middle-aged groups.

This study evaluated the reliability, validity, and responder definitions of the generalized pustular psoriasis physician global assessment (GPPGA) and generalized pustular psoriasis area and severity index (GPPASI)

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Background:
Generalized pustular psoriasis (GPP) is a rare and life-threatening skin disease often accompanied by systemic inflammation. There are currently no standardized or validated GPP-specific measures for assessing severity.

Objective:
To evaluate the reliability, validity, and responder definitions of the generalized pustular psoriasis physician global assessment (GPPGA) and generalized pustular psoriasis area and severity index (GPPASI).

Methods:
The GPPGA and GPPASI were validated using outcome data from Week 1 of the Effisayil™ 1 study. The psychometric analyses performed included confirmatory factor analysis, item-to-item/item-to-total correlations, internal consistency reliability, test-retest reliability, convergent validity, known-groups validity, responsiveness analysis, and responder definition analysis.

Results:
Using data from this patient cohort (N=53), confirmatory factor analysis demonstrated unidimensionality of the GPPGA total score (root mean square error of approximation <0.08), and GPPGA item-to-item and item-to-total correlations ranged from 0.58–0.90. The GPPGA total score, pustulation subscore, and GPPASI total score all demonstrated good test-retest reliability (intraclass correlation coefficient: 0.70, 0.91, and 0.95, respectively), and good evidence of convergent validity. In anchor-based analyses, all three scores were able to detect changes in symptom and disease severity over time; reductions of -1.4, -2.2, and -12.0 were suggested as clinically meaningful improvement thresholds for the GPPGA total score, GPPGA pustulation subscore, and GPPASI total score, respectively. Anchor-based analyses also supported the GPPASI 50 as a clinically meaningful threshold for improvement.

Conclusions:
Overall, our findings indicate that the GPPGA and GPPASI are valid, reliable, and responsive measures for the assessment of GPP disease severity, and support their use in informing clinical endpoints in trials in GPP.

Good morning, I’m wondering if anyone else on here has psoriasis as well as under active thyroid (Hashimoto's). I’m trying to compare the suggested diet do’s and don’ts. I am already gluten free, dairy free, sugar free and nightshade free and don’t eat seafood ?. I would love to know people’s ideas for meals, snacks etc.

I have looked at the food pyramid and have a question about cacao powder. Thoughts on it? Good, bad etc. I like to put 1 tablespoon in my morning smoothie. It’s the only chocolate I have had in over two weeks. As I have read conflicting research on eating chocolate or not with psoriasis. I’m on a very limited diet already and like just that little touch of ?

I am new to all of this. I have a possible diagnosis of psoriasis with a follow up appointment in a couple of weeks with a dermatologist. I do know that if I eat gluten, dairy, nightshade vegetables or sugar I get more spots, flaking and itching. I have eliminated all from my diet but still have mild spots, but no itching. Just trying to figure this all out.

Just wondering if anyone else on Taltz has ever experienced a reaction after using a Hot Tub that you never previously experienced before Taltz?

I had been in Hot Tubs years ago with no reactions, since using Taltz I get extremely itchy rashy areas to my lower legs, arms, pits, and upper torso.

I spoke to my Taltz Nurse and she found no info on anyone complaining of this reaction so she did not think Taltz would be the cause.

We are pleased to join the Psoriasis Club.  It is mainly Tanya who does the computer stuff but it is Mike who has suffered from Psoriasis for years.  Tanya encouraged him to go to a Dermatologist and he got started on some treatments.  The treatments led to trials in Canada for approximately 20 years.  But in the end it was Taltz that I live with now!  Tanya was by my side through all the creams, lotions, IV's, lights, and injections and knows everything from my journey better than I do (can you tell she is typing......LOL).

good morning, i am new here just started otezla and hoping to get some insight on if it actually is helping anyone?

Im on my third dose, soon to be 4th of bimzelx and have noticed spots some almost as big as boils under my arms and on my flanks but i can get them everywhere even on my fingers. i normally have 5 or 6 under each arm/flank and two on each arm.
with cosentyx i started getting a red rash under my armpits. inverted p?  and that hasnt gone away in fact its spread slightly and the spots have come to play as well. they struggle to get a head and im trying to get some fucidin to help. i did get a few spots with cosentyx but nothing like this.

also my face flares up all the time under my beard, and on my forehead.
and ive got p inbetween my toes.

anyone else?

i am alan and live in the uk
i have been on bimzelx for 3 months and prob 90% clear but having some side effects
before that cosentyx successfully for a few ears and before that stelara for many years good for p but not so good for pa
i am 61 years old  barely married, still working and after suffering with p for 42 years i have finally got used to the shame of looking diseased and ugly. i have suffered mental illness anxiety and depression on and off for the same time ive had p.  linked maybe?
ive joined up on here hoping there are people here who can answer a few questions i have about my medication and other aspects of lifestyle changes diet etc to manage my symptoms better.
i am happy and have hobbies including motorbikes (riding and tinkering),  guitar playing, watching football, romance, and boring people to death with long intros on forums.

alan

Comparing Tremfya to Stelara 104-week multicentre retrospective study in Italy.

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Background:
Guselkumab is a humanized monoclonal antibody that binds selectively to the p19 subunit of interleukin-23, which has shown efficacy in patients with previous incomplete response to ustekinumab in the NAVIGATE clinical trial.

Objectives:
We conducted a 104-week multicenter retrospective study to assess the effectiveness and safety of guselkumab in patients affected by plaque psoriasis with an inadequate response to ustekinumab in a real-life setting.

Methods:
Our retrospective study included 233 adults affected by moderate-to-severe plaque psoriasis, enrolled in 14 different Italian centers, and treated with guselkumab after failing therapy with ustekinumab. Patient characteristics and PASI (Psoriasis Area and Severity Index) score at each visit (baseline, weeks 16, 52 and 104) were recorded. The percentages of patients achieving 75%, 90% and 100% (PASI 75, PASI 90 and PASI 100) improvement in PASI, compared with baseline, were registered.

Results:
At week 52, PASI 75 was reached by 89.88% of patients, PASI 90 by 71.43%, PASI 100 by 58.83% and absolute PASI ≤ 2 by 90.48%. At week 104, similar effectiveness results were observed. Compared to the NAVIGATE trial, we observed higher rates of PASI 75/90/100. Patients with the involvement of difficult-to-treat areas were significantly less likely to achieve PASI90 and PASI100 at week 16. Obese patients had significantly lower rates of PASI75 and PASI≤2 at week 52. At week 104, comparable responses were observed among all patients’ subgroups, regardless of BMI status, involvement of difficult-to-treat areas, presence of cardiometabolic comorbidities and concomitant psoriatic arthritis. No significant safety findings were reported throughout the study.

Conclusion:
Our data suggest that the efficacy of guselkumab in patients with inadequate response to ustekinumab for plaque psoriasis in “real-life” clinical practice is comparable with NAVIGATE study with higher percentages of patients achieving PASI90 and PASI100 at weeks 16, 52 and 104.

Does anyone have experience using Ambetter insurance for their Tremphya prescription? I know I need pre-approval but want to see want an Ambetter user might have to say.

Hi all again 

I am off course searching a lot of stuff about psa, and listened to some podcasts where also food was mentioned. I was wondering did some of you had concrete results with certain foods to avoid? That would trigger flares?

Would eating vegetarian help avoiding symptoms of inflammation. 

Like I heard about dairy, sugar, soda and all that. And I understand that smoking and drinking etc would not help off course with this kind of disease.

I was wondering about your experiences and what maybe worked for you (or not). About certain foods, etc lifestyle changes.

Greetings!

Looking at pruritis in different clinical variants of psoriasis.

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Background:
Pruritus, which is the most frequent subjective symptom of psoriasis, may cause significant discomfort, embarrassment, and even interfere with patients normal daily activities. However, the perception of itch in various psoriasis subtypes remains unknown.

Objectives:
The aim of this study was to investigate and to characterize pruritus in different clinical variants of psoriasis.

Methods:
This cross-sectional, binational, multicentre study included 295 subjects suffering from 9 different clinical subtypes of psoriasis: large-plaque psoriasis (n=45), nummular psoriasis (n=32), guttate psoriasis (n=31), scalp psoriasis (n=32), inverse psoriasis (n=23), erythrodermic psoriasis (n=33), palmoplantar psoriasis vulgaris (n=33), palmoplantar pustular psoriasis (n=42) and generalized pustular psoriasis (n=23). Measures included sociodemographic and anthropometric data, detailed pruritus characteristics including but not limited to pruritus intensity, frequency, and extend, as well as psoriasis severity.

Results:
The lifetime prevalence of pruritus in each clinical variant of psoriasis was similar and quite high, reaching up to 100% in some disease subtypes (i.e. nummular psoriasis, scalp psoriasis and generalized pustular psoriasis). Psoriasis severity correlated with pruritus intensity in scalp psoriasis, palmoplantar pustular psoriasis and generalized pustular psoriasis. The age, duration of psoriasis and BMI did not interfere with the intensity of itch.

Conclusions:
Pruritus is highly prevalent in each clinical variant of psoriasis. However, the sensation of itch is very individual, difficult to universally describe even in the same subtype.