Biological therapies, including TNF-alpha, IL12/23, IL17 and IL23 antagonists, adequately control a very high number of patients with moderate-to-severe psoriasis with an excellent long-term safety profile. However, on occasion, patients on biological therapy with stabilized disease or complete remission report episodes of sudden breakthrough psoriasis. To study prospectively in a monocentric tertiary setting, the clinical characteristics of patients presenting a sudden breakthrough psoriasis although completely stabilized (PASI 90-100) under biological therapy. Psoriasis patients treated by biological therapies achieving PASI 90-100 and with stabilized disease for at least 6 months were invited to enter the follow-up study for 5 years. The clinical features of patients presenting a breakthrough psoriasis were described as well as the rescue therapies and outcomes. From the total cohort of 1121 patients with psoriasis receiving biologicals, 985 patients responded to the inclusion criteria. After 5 years, 10/882 cases (1,13%) of breakthrough psoriasis were identified. Two cases were induced by the Köbner phenomenon and 8 cases by severe psychological stress. Rescue therapies included topical very potent corticosteroids or additional injections of the biological. Two patients recovered spontaneously when the stressful event was resolved. In none of the cases, there was a consistency between the breakthrough event and the next scheduled injection, nor the duration of the exposure to the treatment. No biological class or agent could be systematically incriminated. Breakthrough psoriasis is an exceptional event among patients with stabilized psoriasis using biologicals, either triggered by the Köbner phenomenon or by severe psychological stress. The pathogenesis of the breakthrough events could be linked to stress- or Köbner-related immunomodulation, permitting breakthrough psoriasis lesions to appear.

Patients' treatment expectations significantly influence the effectiveness of medical and pharmacological treatments. This clinical proof-of-concept study aimed to enhance treatment outcomes by targeting positive treatment expectations of psoriasis patients beginning systemic anti-psoriatic therapy with secukinumab, an interleukin (IL)-17A antagonist. We randomly assigned patients to three groups: a treatment as usual (TAU) group receiving the standard 300mg dose of secukinumab, a dose-control (DC) group with 75% dose reduction and an experimental (EXP) group receiving the same reduced dose along with a "cover story" designed to positively influence treatment expectations. We evaluated skin symptoms using the Psoriasis Area and Severity Index (PASI), the Dermatology Life Quality Index (DLQI), perceived itch, mood and plasma IL-17A levels at baseline and at 1, 2, 3, 4, 8, 12, and 16weeks post intervention. The study included N = 120 patients (average age = 45.78 years, 34% female). A high baseline expectation level (8.1 of 10 points) was observed across all groups which could not be further increased by the EXP-group's "cover story". The EXP and DC groups did not differ with regard to reaching 75% improvement in PASI scores (PASI75), a DLQI score of 0 or 1 or at least 4 points improvement in itch. Over time, the EXP-group showed a faster decline in PASI scores and anxiety symptoms compared to the DC-group, but less improvement in quality of life. IL-17A levels significantly increased throughout the treatment, with no significant differences between groups despite the 75% dose reduction. This study demonstrates an attempt to modify patients' treatment expectations to enhance the effectiveness of pharmacological therapy with secukinumab in psoriasis patients. However, verbal suggestion alone did not significantly improve clinical outcomes, suggesting that future studies should explore alternative approaches to leverage placebo effects to the benefit of patients with psoriasis.

Current pharmacological treatments for psoriasis are generally non-specific and have significant limitations, particularly in the realm of targeted biologic therapies. There is an urgent need to identify and develop new therapeutic targets to improve treatment options. The aim of this study was to explore the proteome associated with psoriasis in large population cohorts to discover novel biomarkers that could guide therapy. We analyzed data from 54,306 participants enrolled in the UK Biobank Pharmacological Proteomics Project (UKB-PPP). We investigated the relationship between 2923 serum proteins and the risk of psoriasis using multivariate Cox regression models initially. This was complemented by two-sample Mendelian randomization (TSMR), Summary-data-based Mendelian Randomization (SMR), and coloc colocalization studies to identify genetic correlations with protein targets linked to psoriasis. A protein scoring system was created using the Cox proportional hazards model, and cumulative risk curves were generated to analyze psoriasis incidence variations. Our study pinpointed 62 proteins significantly linked to the risk of developing psoriasis. Further analysis through TSMR narrowed these down to ten proteins with strong causal relationships to the disease. Additional deep-dive analyses such as SMR, colocalization, and differential expression studies highlighted four critical proteins (MMP12, PCSK9, PRSS8, and SCLY). We calculated a protein score based on the levels of these proteins, with higher scores correlating with increased risk of psoriasis. This study's integration of proteomic and genetic data from a European adult cohort provides compelling evidence of several proteins as viable predictive biomarkers and potential therapeutic targets for psoriasis, facilitating the advancement of targeted treatment strategies.

Psoriasis is a chronic inflammatory disease with a complex pathogenesis. Hyperplasia of glycolytic-dependent epidermal keratinocytes (KCs) is a new hallmark of psoriasis pathogenesis. Meanwhile, immune cells undergo metabolic reprogramming similar to KCs. Glycolysis provides energy for the proliferation of KCs, while it also releases lactic acid to facilitate the differentiation of immune cells. In turn, differentiated immune cells further promote KCs glycolysis by releasing inflammatory factors, thus forming an immunometabolism loop. The interaction between immune response and metabolic pathways jointly promotes the sustained proliferation of KCs and the secretion of various inflammatory factors by immune cells. Understanding the role of glycolysis in immunometabolism of psoriasis may provide new ideas for non-immunosuppressive treatment of psoriasis. This article aims to review the role of glycolysis in the pathogenesis of psoriasis and attempts to summarize the key enzymes and regulatory factors involved in psoriasis glycolysis, as well as their interactions. Finally, we discuss the pharmacological modulators of glycolysis in psoriasis.

Psoriasis is an immune-mediated skin disease known to be associated with a higher risk of cardiometabolic comorbidities such as hypertension, myocardial infarction, and stroke. GLP-1 receptor agonists (GLP-1RAs) are medications approved to treat type 2 diabetes mellitus and obesity and have been reported to improve psoriasis. As more psoriasis patients start GLP-1RAs for approved indications, it is of interest to understand the impact of GLP-1RAs on both psoriasis and associated cardiovascular risk. In this review, we examine the effect of GLP-1RAs on psoriasis and cardiovascular comorbidities-defined as hypertension, stroke, and myocardial infarction. The majority of case reports and prospective cohort studies found GLP-1RAs improved psoriasis, while two randomized controlled trials showed conflicting results. For cardiovascular disease, most studies found GLP-1RAs reduced systolic blood pressure, total stroke, and myocardial mortality. These results suggest that GLP-1RAs may be a particularly promising treatment for psoriasis patients with diabetes or obesity comorbidities, offering both cardioprotective benefits and potential improvement in psoriatic symptoms.

This prospective observational study investigated whether interleukin (IL)-17A inhibitors could reduce serum uric acid (SUA) levels in psoriatic patients with hyperuricemia. It also explored the risk factors for hyperuricemia in psoriatic patients and the effectiveness of IL-17A inhibitors for the skin lesions of psoriatic patients with hyperuricemia. Patients aged ≥18 years with moderate to severe plaque psoriasis along with concomitant hyperuricemia (defined as an SUA level >416μmol/L in men and >357μmol/L in women) at baseline were treated with either secukinumab or ixekizumab. SUA levels were longitudinally assessed over 1 year. We evaluated the changes in SUA level and factors associated with SUA changes. Binary logistic regression was conducted to identify risk factors for hyperuricemia in psoriatic patients. Additionally, we examined effectiveness of IL-17A inhibitors for patients with psoriasis and hyperuricemia including Psoriasis Area Severity Index (PASI) 75, 90, and 100 response rates at 1 year. Our study included 196 individuals diagnosed with psoriasis and hyperuricemia. The mean SUA levels were 481±68μmol/L at baseline and 442±78μmol/L after 1 year of treatment with IL-17A inhibitors (p<0.001). Subgroup analysis revealed a consistent and significant decrease in SUA levels across different genders, age groups (30-39, 40-49, ≥50 years), BMI categories, baseline PASI scores, PASI improvement rates, and among patients treated with different IL-17A inhibitors. Patients aged ≥50 years and with a BMI <24 exhibited a higher SUA reduction rate. Male gender, age under 40 years, obesity, hypertension, hypertriglyceridemia, and a PASI score of ≥20 were independent risk factors for hyperuricemia in patients with psoriasis. The PASI 75, 90, and 100 response rates in psoriatic patients with hyperuricemia were 88.3%, 60.2%, and 28.6%, respectively, after 1 year of treatment with IL-17A inhibitors. Our findings suggest that SUA levels decrease significantly under IL-17A inhibitors treatment in psoriatic patients with hyperuricemia. Patients aged ≥50 years and with a BMI <24had greater benefits. This study provides a theoretical basis for the selection of biologics to treat psoriatic patients with hyperuricemia.

This real-world study investigated the impact of patient-reported disease burden and health-related quality of life (HRQoL) on switching from systemic nonbiologic to biologic therapy in patients with plaque psoriasis. Biologic therapy-naive (biologic-naive) patients aged ≥18 years who were using systemic nonbiologic treatment and who enrolled in the CorEvitas Psoriasis Registry between April 2015 and August 2022 were included. Measures of patient-reported disease burden and HRQoL were collected at Registry enrollment. The primary outcome of interest was initiation of biologic therapy within 45 days of enrollment. Multivariable logistic regression models were fitted separately for each patient-reported measure, adjusting for patient, disease, and treatment characteristics, including physician-rated disease severity. Adjusted odds ratios of switching to biologic therapy were estimated for greater versus lesser burden for each measure. Of 848 included patients, 323 (38.1%) switched to biologic treatment. Greater patient-reported burden was independently associated with switching, with significantly higher adjusted odds ratios (95% confidence interval) for greater versus lesser burden as measured by the Dermatology Life Quality Index (1.55 [1.08-2.23], P=0.017), visual analog scale (VAS) for itch (2.14 [1.49-3.08], P<0.001), VAS for skin pain (2.18 [1.45-3.29], P<0.001), VAS for fatigue (1.66 [1.15-2.40], P=0.007), Patient Global Assessment-VAS (3.09 [1.94-4.91], P<0.001), and with activities impairment on the Work Productivity and Activity Impairment questionnaire (2.51 [1.72-3.65], P<0.001). In addition to clinically assessed disease severity, patient-reported disease burden and quality of life may drive the switch to biologic treatment in real-world patients with plaque psoriasis.

Acrodermatitis enteropathica (AE) can be caused by inherited or acquired zinc deficiency, among which site-specific skin lesions or even psoriasiform skin manifestations are present. Few cases exist in the literature involving the diagnosis and treatment of AE overlapped with psoriasiform lesions. In this case, we reported a teenage boy presented characteristic site-specific skin lesions of AE with low serum zinc level, subsequently progressed into generalized pustular psoriasiform manifestations under a genetic background, while a rapid recovery was observed after monotherapy of zinc supplementation. Since zinc malabsorption was suspend to be the trigger of both AE and psoriasiform lesions, simply maintaining balanced zinc homeostasis might be a safe and effective treatment for the overlapped manifestations.

Psoriasis is a chronic, immunologically mediated disease of multifactorial origin, with genes playing a key role and environmental factors, such as infections, often triggering its onset or exacerbation. While acute streptococcal infections are commonly linked to guttate psoriasis, viral and fungal infections have also been associated with psoriasis flares. We report a case of severe psoriasis exacerbation during viral parotitis caused by paramyxovirus in a 49-year-old male patient with a long-standing psoriasis diagnosis. Following successful treatment with secukinumab, the patient experienced a flare-up coinciding with symptoms of mumps infection. Serological tests confirmed the presence of mumps virus RNA. Secukinumab was discontinued, and treatment with risankizumab resulted in rapid remission of psoriasis. While paramyxovirus infections are not typically associated with psoriasis flares, emerging evidence suggests that dysregulated antiviral immune responses may induce IL-23 production, possibly contributing to inflammation in psoriasis. This case highlights the need for further research on the role of antiviral immune responses in psoriasis exacerbations and the potential therapeutic implications of targeting the IL-23 pathway.