Just wondered how many of you on here who suffer with psoriasis, also suffer, or
Have suffered, with sinus problems at some point in your life?

This Swedish study looked at compulsory military service in men and psoriasis.

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Background:
Although stress is considered to be a negative factor for psoriasis, no convincing scientific evidence of this association exists, largely because of difficulties in measuring stress. Stress resilience is the ability to cope with and adapt to stressful events. Stress resilience can be measured in a standardized way and used as a marker for chronic stress.

Objectives:
The objective of this study is to investigate whether low stress resilience in adolescence increases the risk for onset of psoriasis and psoriatic arthritis later in life.

Methods:
A cohort of Swedish men (mean age 18.3 years), enrolled in compulsory military service between 1968 and 2005, was created using data from the Swedish Military Service Conscription Register (n = 1,669,422). Stress resilience at conscription was estimated using standardized semi-structured interviews, and was divided into three categories: low, medium and high. The men were followed from conscription until new-onset psoriasis or psoriatic arthritis, death or emigration or at the latest until 31 December 2019. Cox regression models adjusted for confounders at conscription were used to obtain hazard ratios (HRs) with 95% confidence intervals (CIs) for incident psoriasis and psoriatic arthritis.

Results:
Men in the lowest stress resilience category had an increased risk of psoriasis and psoriatic arthritis (HR 1.31 (95% CI 1.26–1.36) and 1.23 (95% CI 1.15–1.32), respectively), compared with those in the highest stress resilience category. When including only hospitalized patients the HRs for psoriasis and psoriatic arthritis in the lowest stress resilience group were 1.79 (1.63–1.98) and 1.53 (1.32–1.77), respectively.

Conclusions:
This large, prospective register study suggests that low stress resilience in adolescence is associated with an increased risk of incident psoriasis among men. The results indicate that patients with psoriasis have an inherent psychological vulnerability, and highlight the importance of addressing psychological well-being in the management of psoriasis.

This study looked evaluated the potential of serum protein levels as predictive biomarker candidates whilst using Tremfya (guselkumab)

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Background:
Response to biologics in psoriasis varies in real-world settings. Serum biomarkers could aid biologic selection and dose modifications to improve patient outcomes while encouraging cost-effective care.

Objectives:
To explore the exposure–response relationship for guselkumab (GUS), to define a GUS concentration target for optimal response and to evaluate the potential of serum protein levels as predictive biomarker candidates.

Methods:
This is a prospective, multicentric, cohort study in psoriasis patients treated with GUS. Serum GUS trough concentrations (TCs) collected at multiple timepoints were measured using an in-house immunoassay. Next, proximity extension assay technology (Target 96 Inflammation Panel Olink®) was used to measure serum protein levels in a subcohort including 38 GUS patients (week 0 and week 4), six psoriasis patients naive for systemic treatment and four healthy controls.

Results:
Seventy-five patients participated and 400 samples were collected. Guselkumab TCs and clinical response were correlated at week 4, week 12 and in steady-state (≥20 weeks). Optimal responders (Psoriasis Area and Severity Index [PASI] ≤ 2) had significantly higher TCs than suboptimal responders from week 4 onwards in treatment. An optimal steady-state TC of 1.6 μg/mL was defined. Although TC and absolute PASI were lower and worse, respectively, in patients weighing ≥90 kg, clinical outcomes referred to desirable to excellent PASI ranges. Therefore, we do not recommend systematically higher GUS doses in obese patients. We could not reveal early differentially expressed proteins to distinguish future optimal from suboptimal responders.

Conclusions:
We demonstrated an exposure–response relationship for GUS and an optimal steady-state TC of 1.6 μg/mL in real-world psoriasis patients. Hereby, we deliver more evidence that therapeutic drug monitoring poses a promising strategy in optimizing GUS treatment. No biomarker candidates were identified through serum proteomics. We propose protein screening should be repeated in larger cohorts to continue the quest for predictive biomarkers.

This German study looked at effectiveness, safety and impact of Tremfya (guselkumab) on sexuality and perceived stigmatization in patients with psoriasis.

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Background:
G-EPOSS is a prospective, non-interventional, German multicentre study of patients with moderate-to-severe plaque psoriasis receiving guselkumab, a therapeutic monoclonal antibody targeting interleukin-23, in a real-world setting.

Objectives:
The objective of the study was to evaluate the effectiveness and safety of guselkumab, including its impact on skin, health-related quality of life (HRQoL), sexuality, and perceived stigmatization.

Methods:
Patients (≥18 years old) received guselkumab per routine clinical practice. The primary endpoint was the proportion of patients achieving absolute Psoriasis Area and Severity Index (PASI) ≤ 3 at Week (W)28. Secondary endpoint assessments over 28 weeks included the Nail Psoriasis Severity Index (NAPSI), anogenital Physician's Global Assessment (aPGA), and Dermatology Life Quality Index (DLQI). Sexuality and perceived stigmatization were assessed by patients using the Relationship and Sexuality Scale (RSS) and Perceived Stigmatization Questionnaire (PSQ), respectively.

Results:
Overall, 293 patients were included in the evaluable set population. Mean age and disease duration were 45.6 and 17.6 years, respectively. At baseline, mean PASI, aPGA and DLQI scores were 15.3, 2.7 and 11.3, respectively. In total, 25.9% of patients had received a prior biologic. Overall, 83.0% of patients achieved PASI ≤ 3, and 56.2%/35.1% achieved PASI ≤ 1/PASI = 0, respectively, at W28. Among those with NAPSI ≥ 1 and aPGA ≥ 1 at baseline, NAPSI = 0 and aPGA = 0 were achieved by 39.2% and 61.1% of patients, respectively, and 61.4% of patients achieved DLQI 0–1 at W28. Improvements were observed over 28 weeks across individual items of the DLQI, RSS and PSQ, indicating improved HRQoL and sex life, and decreased perceived stigmatization. Based on DLQI Question (Q)9, 53.6% of patients experienced sexual difficulties at baseline, which decreased to 12.1% at W28. DLQI Q9 responses were consistent with RSS item responses, highlighting DLQI Q9 as a sentinel for sexual impairment.

Conclusions:
Guselkumab improved overall skin symptoms and HRQoL in patients with psoriasis and decreased sexual impairment and perceived stigmatization. No new safety signals were observed.

This study was passed to me by afternoonfix

Scientists from The Australian National University (ANU) have discovered a gene mutation is responsible for causing psoriasis.

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According to ANU researcher Dr Chelisa Cardinez, if two copies of this mutated gene (known as IKBKB) are present, patients with psoriasis may go on to develop psoriatic arthritis, leaving them with joint pain, stiffness and swelling. Thanks to the world-first discovery from ANU, scientists now know what causes the progression from a skin-only disease to a skin and joint disease.

It’s hoped the findings will lead to improved diagnosis and treatment for patients with psoriasis and psoriatic arthritis – conditions that patients say carry stigma in the community.

“Using a mouse model, we identified that this mutation led to an abnormal function in a group of immune cells known as regulatory T cells,” Dr Cardinez, from the ANU John Curtin School of Medical Research (JCSMR), said.

“These cells are normally considered gatekeepers of the immune system. However, we found that this mutation alters the function of these cells, causing them to contribute to inflammation and promote the onset of disease.”

Dr Cardinez said: “Studies have shown that delays in psoriatic arthritis diagnosis is linked to worse clinical outcomes for patients. Therefore, earlier detection and treatment of these immune diseases is key to improving health outcomes.

"By developing a better understanding of the IKBKB gene and the role it plays in promoting the onset of these diseases, it could bring us a step closer to one day finding a cure.

Hi there,

I've been using Enstilar foam with good results for a while now, but ever since I started using it, I developed a red rash around my nose and chin. At first I though it was down to a milk allergy I have, but I stopped using Enstilar for 3 days and the rash went away. I then started using it again and the rash came back. From looking online, it seems that it's allergic contact dermatitis, caused by Butylated Hydroxytoluene.
Does anyone else have any experience with this? And does anyone know if there's a particular antihistamine that could combat this? I tried using a hydrocortisone directly on the rash, but that didn't do much.

Any help would be much appreciated. Thank you.

Well, after a seemingly endless wait I'm finally on Imraldi.

I've had three injections in the last two weeks and can already see an improvement in some patches on my arms and side, though my legs have yet to take notice.

My derm has yet to sort my blood tests out but hopefully they'll be fine. I'll try and keep you updated with progress and fingers crossed for good results.

This French population based real world cohort study looked at pustular psoriasis (GPP)

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Background:
GPP is a rare, chronic, neutrophilic skin disease, with limited real-world data characterizing patients with flares and the impact of flares on disease progression and morbidity.

Objective:
Describe the clinical characteristics of patients with GPP, comorbidities, disease epidemiology and frequency and severity of flares, and compare patients with GPP with a matched severe psoriasis population.

Methods:
In this population-based real-world cohort study an algorithm was developed to identify patients with GPP flares. Three cohorts were identified using the Système National des Données de Santé (SNDS) database covering almost the entire French population; a prevalent cohort (2010–2018), an incident cohort (2012–2015). A severe psoriasis cohort was compared with the GPP incident cohort using propensity score matching.

Results:
The prevalent and incident cohorts comprised 4195 and 1842 patients, respectively. In both cohorts, mean age was 58 years; 53% were male. Comorbidities were significantly more common in the incident cohort versus matched psoriasis cohort, respectively, including hypertension (44% vs. 26%), ischaemic heart disease (26% vs. 18%) and hyperlipidaemia (25% vs. 15%). In the incident cohort, the flare rate was 0.1 flares/person-year and 0.4 flares/person-year among the 569 out of 1842 patients hospitalized with flares. These patients had a mean (±SD) stay of 11.6 ± 10.4 days; 25% were admitted to the intensive care unit. In 2017, the cumulative incidence and cumulative GPP age–sex standardized prevalence were 7.1 and 45.2 per million, respectively.

Conclusions:
Patients with GPP had a distinct comorbidity profile compared to patients with severe psoriasis, and GPP flares were associated with long hospitalizations.

This study looked at  generalized pustular psoriasis (GPP) in Central and Eastern Europe.

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Background:
Generalized pustular psoriasis (GPP) is a rare, inflammatory skin disease characterized by widespread eruption of sterile pustules with or without systemic symptoms.

Objectives:
This study aimed to describe the demographics of patients with GPP in Central and Eastern Europe (CEE), present the clinical characteristics of individual GPP flares and explore the current treatment landscape.

Methods:
Patient demographics were collected at the times of last observation and previous treatment. Characteristics of a patient's last (most recent) and most severe (from all documented episodes) flare were provided at clinician's discretion.

Results:
Fifty-eight patients were recruited from 12 centres in nine CEE countries; median (range) age was 61 (16–92) years and 60.3% (35 out of 58) were female. The most common comorbidities were hypertension (43.1% [25 out of 58]) and hyperlipidaemia (32.8% [19 out of 58]). Thirty-four patients (58.6%) presented with concomitant plaque psoriasis before or during the course of GPP. Data from two separate flares were recorded in 26 individuals; in 32 patients, the most recent flare was reported as the most severe. Over 90% of patients with a flare episode classified as most severe by clinicians were hospitalized, with >75% of these individuals having a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) total score of 3 or 4. Systemic symptoms were more common in patients with a GPPGA score of 3 or 4 but were also manifest in individuals with a GPPGA score ≤2. A significant correlation was observed between a combined systemic disease score of clinical and laboratory features and both GPPGA total score (r = 0.385, p < 0.001) and GPPGA pustulation subscore (r = 0.305, p < 0.05).

Conclusions:
Considerable heterogeneity in the presentation of GPP flares was observed, both between patients and within-patient. All GPP flares were associated with a significant clinical burden, highlighting the unmet need for accurate and early diagnosis.

has anyone any experience in this? i only have a small patch of flexural psoriasis (groin area) about the size of a hand palm, but it is sore (3 out of 5) and itchy (again 3 out of 5) have tried hydrocortisone (1%) ointments, eumovate (0.05% w/w clobetasone butyrate) Silkis (calcitriol 3 mg / 1gm ointment. emmolients such as Diprobase & Epaderm for moisturing. I still have the pustular rash that i started with about 3 months ago. it wans but never really disappears completely. I am currently on a treatment break as directed by GP. I have read on other forums about increasing Vitamin D3 helps may other psoriasis sufferer's and have seen varying levels of dosage, from 1000mg to 10,000mg. I was looking for thoughts about this from the users here...any advice anyone? thanks in advance

These results follow on from this thread Piclidenoson submits registration plans for psoriasis

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Objective:
A3 adenosine receptor (A3AR) is overexpressed in the skin and peripheral blood mononuclear cells of psoriasis patients. We investigated the efficacy/safety of piclidenoson (CF101), an orally bioavailable A3AR agonist that inhibits IL-17 and IL-23 production in keratinocytes, in moderate-to-severe plaque psoriasis.

Methods:
The randomized, placebo- and active-controlled, double-blind phase 3 COMFORT-1 trial randomized patients (3:3:3:2) to piclidenoson 2 mg BID, piclidenoson 3 mg BID, apremilast 30 mg BID or placebo. At Week 16, patients in the placebo arm were re-randomized (1:1:1) to piclidenoson 2 mg BID, piclidenoson 3 mg BID or apremilast 30 mg BID. The primary end point was the proportion of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI) from baseline (PASI-75) at Week 16 versus placebo.

Results:
A total of 529 patients were randomized and received ≥1 dose of study medication (safety population). The efficacy analysis population for the primary end point included 426 patients (piclidenoson 2 mg BID, 127; piclidenoson 3 mg BID, 103; apremilast, 118; placebo, 78). Piclidenoson at 2 and 3 mg BID exhibited similar efficacy. The primary end point was met with the 3 mg BID dose: PASI 75 rate of 9.7% versus 2.6% for piclidenoson versus placebo, p = 0.037. The PASI responses with piclidenoson continued to increase throughout the study period in a linear manner. At week 32, analysis in the per-protocol population showed that a greater proportion of patients in the piclidenoson 3 mg BID arm (51/88, 58.0%) achieved improvement from baseline in Psoriasis Disability Index (PDI) compared to apremilast (59/108, 55.1%), and the test for noninferiority trended towards significance (p = 0.072). The safety/tolerability profile of piclidenoson was excellent and superior to apremilast.

Conclusions:
Piclidenoson demonstrated efficacy responses that increased over time alongside a favourable safety profile. These findings support its continued clinical development as a psoriasis treatment.

I will link my first thread here (or ask Fred to) once it's determined how he wants to handle it.  However, I wanted a bit more uncluttered thread that deals with my experience of actually using Skyrizi.


Today I received my Skyrizi:




It was nicely packaged and as you can see the card has the white dot meaning that the temperature wasn't compromised (it would be red otherwise)

Two pens, Week 0 and week 4 (the next one will be week 16, I'll call for a refill at about 4 weeks before it's due)

Not much paperwork, one page describing how the temperature card works which a simple sentence of white is good and red is bad would have sufficed, but it was an in depth explanation which is expected when it comes to medical stuff.

4 pages of information.  Describing what Skyrizi is, side effects, etc.  Things you'd find on the webpage.

It came in an insulated box with two ice packs,

So, I'm not really ready for some reason but I will inject later today or tomorrow. 

I have psoriasis under 2 finger nails. Luckily for me 1 has cleared up (mostly) but my thumb nail is tough as old boots and I keep it short so I don’t catch it. I now have psoriasis under one toe nail. It’s lifting off and I’m unsure whether to cut it right down as far as possible as it sometimes catches on my sock. It’s only lifting on the left side but it’s nearly down to the bottom and I’m concerned it’ll get ripped off and that’ll hurt! Can anyone advise please.

I started seeing a new dermatologist. As we were going over medical history stuff, I mentioned that I had been diagnosed with NAFLD (nonalcoholic fatty liver disease) and she replied that was common for people with psoriasis. Which surprised me a bit as I hadn't heard that before, nor had it been mentioned to me so I did a little looking up on the internet to see what I could find. I found the following information which seemed to explain it best:

Although many people think of psoriasis primarily as a skin disease, it is a systemic condition that affects other organs as well. People with psoriasis have increased inflammation throughout the body, which increases the risk of developing comorbid conditions (more than one chronic disease at the same time). For example, people with psoriasis have a higher prevalence of fatty liver disease compared to the general population.

Psoriasis is associated with a higher risk for developing obesity (high body mass index), insulin resistance, and metabolic syndrome — factors that can also increase the risk of NAFLD. A person may be diagnosed with metabolic syndrome if they have three of the following:

Abdominal obesity
High triglyceride levels
Low HDL cholesterol levels
High glucose levels
Hypertension (high blood pressure)
People with metabolic syndrome and severe psoriasis are at a higher risk of developing NAFLD.

I tick quite a few of those. Also with inflammation being mentioned it has made me wonder about other things going on with me and how it all ties in together. Of course having arthritis is a factor for the inflammation as well.

So now I'm really hopeful to see how Skyrizi will work out for me (calling them next week to have them ship to me). Maybe if my psoriasis is calmed down so might some other stuff? It would be nice if it works that way!

Efficacy of long-term Skyrizi (risankizumab) treatment for moderate-to-severe plaque psoriasis over 256 weeks.

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Background:
Psoriasis is an inflammatory skin disease that impacts a heterogeneous group of patients and can have multiple clinical manifestations. Risankizumab is approved for the treatment of moderate-to-severe plaque psoriasis.

Objectives:
To evaluate the long-term efficacy of risankizumab according to baseline patient characteristics, and for the treatment of high-impact disease manifestations (nail, scalp and palmoplantar psoriasis), through 256 weeks of continuous treatment in the phase 3 LIMMitless study.

Methods:
This subgroup analysis evaluated pooled data from patients with moderate-to-severe plaque psoriasis who were randomized to risankizumab 150 mg during two double-blind, phase 3, 52-week base studies (UltIMMa-1/2; NCT02684370/NCT02684357) and were enrolled in the phase 3 LIMMitless open-label extension study (NCT03047395). Subgroup assessments included the proportion of patients who achieved ≥90%/100% improvement in Psoriasis Area and Severity Index (PASI 90/100). Among patients with nail, scalp and/or palmoplantar psoriasis in addition to skin psoriasis, assessments included changes from baseline in and resolution of these three psoriatic manifestations.

Results:
Overall, a numerically similar proportion of patients (N = 525) achieved PASI 90/100 through Week 256, regardless of their baseline age, sex, body mass index, weight, PASI or psoriatic arthritis status. Patients with nail, scalp and/or palmoplantar psoriasis experienced substantial improvements in manifestation-specific indices (mean improvement from baseline to Week 256 of >81%, >94% and >97%, respectively); in patients with all three manifestations (N = 121), 44.6% achieved complete clearance of these manifestations at Week 256.

Conclusions:
Risankizumab demonstrated generally consistent efficacy through 256 weeks across patient subgroups and showed durable long-term efficacy for psoriatic disease manifestations.

This study looked at pharmacogenetic biomarkers for Cosentyx (secukinumab) response in psoriasis patients.

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Background:
Prediction of the response to a biological treatment in psoriasis patients would allow efficient treatment allocation.

Objective:
To identify polymorphisms associated with secukinumab response in psoriasis patients in a daily practice setting.

Methods:
We studied 180 SNPs in patients with moderate-to-severe plaque psoriasis recruited from 15 Spanish hospitals. Treatment effectiveness was evaluated by absolute PASI ≤3 and ≤1 at 6 and 12 months. Individuals were genotyped using a custom Taqman array. Multiple logistic regression models were generated. Sensitivity, specificity and area under the curve (AUC) were analysed.

Results:
A total of 173 patients were studied at 6 months, (67% achieved absolute PASI ≤ 3 and 65% PASI ≤ 1) and 162 at 12 months (75% achieved absolute PASI ≤ 3 and 64% PASI ≤ 1). Multivariable analysis showed the association of different sets of SNPs with the response to secukinumab. The model of absolute PASI≤3 at 6 months showed best values of sensitivity and specificity. Four SNPs were associated with the capability of achieving absolute PASI ≤ 3 at 6 months. rs1801274 (FCGR2A), rs2431697 (miR-146a) and rs10484554 (HLCw6) were identified as risk factors for failure to achieve absolute PASI≤3, while rs1051738 (PDE4A) was protective. AUC including these genotypes, weight of patients and history of biological therapy was 0.88 (95% CI 0.83–0.94), with a sensitivity of 48.6% and specificity of 95.7% to discriminate between both phenotypes.

Conclusion:
We have identified a series of polymorphisms associated with the response to secukinumab capable of predicting the potential response/non-response to this drug in patients with plaque psoriasis.

Had my cataracts done recently and got some psoriasis on one eyebrow, I think the sticky tape to keep the eye shield in place has made it flare though it didn't in the first one.

Obviously I can't use anything near the eye at the moment so I'm trying the good old substitute of coconut oil, I'll see how it goes.

This study looked at the effectiveness and safety of Taltz (ixekizumab) over 5 years.

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Introduction:
Ixekizumab proved to be effective and safe for psoriasis treatment in several randomized clinical trials and real-life studies. Nevertheless, long-term real-world experiences are still lacking, with little data up to 4 years of treatment.

Objectives:
To analyse survival, effectiveness and safety of ixekizumab in a real-life cohort of patients affected by moderate-to-severe psoriasis or psoriatic arthritis up to 260 weeks (5 years).

Methods:
We included all patients treated with ixekizumab from December 2017 to March 2021. Drug survival (DS) was analysed in patients at risk for up to 5 years. Cox analysis was adopted to evaluate possible predictive factors of discontinuation. Psoriasis Area Severity Index (meanPASI and PASI100, 90, and ≤3) was used as outcomes of effectiveness on observed patients at 16, 52, 104, 156, 208 and 260 weeks. Logistic regression was performed to identify possible predictive factors of response.

Results:
DS was 65.5% at 260 weeks, with being a super-responder patient (achievement of PASI100 at 16 weeks and maintained at 28 weeks) correlated with less risk of discontinuation. PASI100, 90 and ≤3 was achieved by 54.1%, 60.5% and 73% of observed patients, respectively, at 16 weeks, and by 59.1%, 81.8% and 95.5%, respectively, at 260 weeks. High mean BMI was the only factor strongly associated with less achievement of the outcomes at the earlier time points: PASI100 at 16 weeks (OR 0.93, CI 0.87–0.98, p = 0.014) and at 104 weeks (OR 0.91, CI 0.84–0.98, p = 0.019), PASI90 achievement at 16 weeks (OR 0.94, CI 0.88–0.99, p = 0.028) and 104 weeks (OR 0.91, CI 0.83–0.99, p = 0.027), and PASI ≤3 (OR 0.86, CI 0.76–0.97, p = 0.018) at 104 weeks. No severe adverse events were observed.

Conclusions:
Ixekizumab showed high effectiveness and safety for up to 5 years, with survival of 2/3 of treated patients. Rapid response to treatment is predictive of long-term response.

This small study looked at dry eye syndrome (DES) in patients with psoriasis.

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Background:
Psoriasis is one of the most common dermatoses associated with a variety of comorbidities. There have been some reports on its possible association with ocular disorders however dry eye syndrome (DES) in such patients has been poorly investigated.

Objectives:
To investigate the frequency of DES symptoms in psoriatic patients, also regarding psoriasis severity in PASI, manifestation and therapy.

Methods:
40 patients with psoriasis and 40 volunteers without dermatoses were enrolled in the study. They completed Ocular Surface Disease Index (OSDI) questionnaire and were objectively examined by IDRA® device to perform automatic interferometry, automatic meibography of lower eyelid glands, non-invasive break-up time (NIBUT), blink quality and tear meniscus height.

Results:
Patients with psoriasis had statistically significantly thicker lipid layer (p = 0.0042 left eye, p = 0.0313 right eye) and greater loss of Meibomian glands compared to controls (p = 0.0128 left eye, p = 0.048 right eye). The patients had lower, although insignificantly, eye blink quality and tear meniscus height than the control group, as well as shorter NIBUT and higher score in OSDI. After the division of patients into two groups–with or without nails involvement/psoriatic arthritis/systemic treatment– we did not observe any significant differences between the groups. PASI did not correlate with any DES parameter.

Conclusions:
This is the first study of DES symptoms with an objective IDRA® analyzer. We managed to observe that patients with psoriasis have thicker lipid layer and higher Meibomian glands' loss in lower eyelids. Based on all assessed objective and subjective parameters psoriatics do not seem to have an increased risk of DES. The presence of psoriatic arthritis or nail involvement does not seem to be a predisposing factor for DES development. PASI probably cannot be a prognostic factor for any of the DES-associated parameters. Nevertheless, DES in psoriasis requires further research on bigger samples to establish reliable recommendations.

This study looked at T-lymphokine-activated killer cell-originated protein kinase (TOPK) as a possible new target for treating psoriasis.

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Background:
Psoriasis is an inflammatory skin disease. The pathogenesis of psoriasis has not been fully elucidated. T-lymphokine-activated killer cell-originated protein kinase (TOPK) activity increases in a proinflammatory environment, and inhibiting TOPK blocks inflammation. However, whether TOPK is involved in the pathogenesis of psoriasis remains to be identified.

Objectives:
We aimed to study the role of TOPK in psoriasis and attempted to find a drug targeting TOPK for the prevention and treatment of psoriasis.

Method:
Firstly, the expressions of TOPK in psoriatic patients, psoriatic cell and animal model were analysed by Gene Expression Omnibus database, immunohistochemistry (IHC) staining and western blot (WB). After inhibiting TOPK by chemical or gene knockout, the effect of TOPK on the development of psoriasis was verified in cell and animal model by WB, qRT-PCR, ELISA, haematoxylin–eosin (H&E) and IHC staining. Moreover, phosphoproteomic analysis was performed to explore the signalling pathways regulated by TOPK in the occurrence and development of psoriasis. Then, an in vitro kinase assay was performed to prove TOPK kinase activity was inhibited by worenine. Ultimately, WB, qRT-PCR, ELISA, H&E and IHC staining were used to verify the anti-psoriasis effect of worenine by inhibiting TOPK was in cell and animal model.

Results:
In this study, we found that TOPK was highly expressed in psoriasis patients, psoriatic cell and animal model, which suggests that TOPK might be associated with psoriasis pathogenesis. Interestingly, chemical or genetic inhibition of TOPK alleviated M5- and imiquimod (IMQ)-induced psoriasis-like dermatitis, which further confirmed the role of TOPK in promoting the development of psoriasis. Moreover, we determined that worenine inhibited TOPK kinase activity. In addition, worenine relieved M5- and IMQ-induced psoriasiform dermatitis by inhibiting TOPK activity.

Conclusions:
T-lymphokine-activated killer cell-originated protein kinase promotes the development of psoriasis. Therefore, TOPK might be a promising drug target for the prevention and treatment of psoriasis. Worenine alleviates psoriasiform dermatitis by inhibiting TOPK activity, providing new strategies for clinical intervention.