tbuckley/cabot-search huggingface dataset:
P51 Plaque psoriasis patients with psoriatic arthritis demonstrate a reduced regulatory capacity for neutrophil elastase compared with plaque psoriasis patients without arthritis
Journal: British Journal of Dermatology (2024)

Abstract Identifying which patients with psoriasis (PsO) may develop psoriatic arthritis (PsA) is a research priority. We have previously shown that Elafin along with IL-36g are excellent cutaneous biomarkers for PsO. The protease inhibitor Elafin and its target protease, neutrophil elastase (NE), can be detected in both serum and epidermal samples. Our aims were to assess if known PsO biomarkers are expressed differentially in patients affected by plaque PsO with and without PsA. Protein expression of NE and Elafin were analysed in matched epidermal samples and serum of PsO, PsA patients and healthy controls. Findings were validated in independent PsA and arthritis cohorts. The ratio between NE and Elafin differed significantly between PsO and PsA patients. Expression of elafin was reduced in PsA samples as compared with plaque PsO patients. The ratio of NE to secretory leukocyte protease inhibitor was also increased in PsA as compared with PsO patients with no PsA, healthy controls and other arthritis patients. PsA patients show a reduced NE inhibitor expression in both the skin and blood compartment compared with those with plaque PsO only. This may suggest differences in the ability to regulate neutrophil activity in PsA patients.
P132 Psoriasis and health economic impact in a developing country like Nepal
Journal: British Journal of Dermatology (2024)

Abstract Introduction Psoriasis is a chronic, inflammatory skin disorder affecting millions globally. In low-income countries like Nepal, the economic burden of managing psoriasis is compounded by limited healthcare resources, inadequate access to treatments, and socio-economic constraints. Aim To assess the prevalence and severity of psoriasis in Nepal. To evaluate the direct and indirect economic costs associated with psoriasis management. To identify gaps in healthcare infrastructure and access to treatment. To propose cost-effective strategies to improve psoriasis care and reduce its economic impact. A mixed-methods approach was employed for a year, including:Epidemiological analysis: Reviewed existing literature and health records to estimate psoriasis prevalence and severity in Nepal.Cost analysis: Calculated direct costs (medical expenses, hospital visits, medications) and indirect costs (loss of productivity, absenteeism) through patient surveys and healthcare data.Qualitative interviews: Conducted in-depth interviews with healthcare providers, patients, and policymakers to understand the barriers to effective psoriasis management.Policy review: Analysed national health insurance policies and their effectiveness in addressing psoriasis care. Results Prevalence: Approximately 2–3% of the Nepalese population is affected by psoriasis, with varying degrees of severity. Economic burden: The average annual cost per patient is significant, encompassing medical expenses, travel costs for treatment, and loss of income due to reduced work capacity. Healthcare gaps: Limited availability of dermatologists, high cost of biologic treatment which is not easily available, taking OTC drugs and lack of public awareness are major barriers. Patient impact: Psoriasis patients in Nepal face considerable socio-economic challenges, including stigma, reduced quality of life, and mental health issues. Conclusion The findings indicate that psoriasis imposes a substantial economic burden on both individuals and the healthcare system in Nepal. The lack of specialized care in rural areas and high treatment costs exacerbate this burden. There is an urgent need for integrated healthcare approaches, increased health insurance facility for psoriasis care, and public health initiatives to raise awareness and reduce stigma. Addressing the health economic impact of psoriasis in Nepal requires a multifaceted strategy, including policy reforms, improved access to affordable treatments, and enhanced healthcare infrastructure. By implementing cost-effective and sustainable interventions, it is possible to alleviate the economic burden of psoriasis and improve the quality of life for affected individuals.
P79 Long-term psoriasis management: the role of NB-UVB phototherapy and topical Cal/BD foam
Journal: British Journal of Dermatology (2024)

Abstract Many psoriasis patients struggle to achieve long-term disease control despite numerous treatment options. Recent research suggests that some biological treatments may lead to sustained, drug-free disease control by targeting underlying immunological factors, though the exact mechanisms remain unclear. This emphasizes the need to identify treatments that contribute to longer-lasting remission. As topical treatments are essential in psoriasis management, it is crucial to determine their role alongside more advanced therapies and how they can be combined for long-term remission. This study aimed to evaluate the efficacy of full-body narrowband UVB (NB-UVB) phototherapy combined with placebo and calcipotriene/betamethasone dipropionate (Cal/BD) foam in 12 patients with plaque psoriasis. Using an open-phase, non-randomized, single-group split-body design (ClinicalTrials.gov: #NCT05185258; Danish Regional Research Ethics Committee: #78623), each patient had two plaques designated for once-daily application of Cal/BD and placebo foam at baseline. After 4 weeks, applications were reduced to twice weekly until end of treatment (EOT). During the first 8 weeks, patients received NB-UVB sessions three times weekly. Study visits were conducted at baseline (week 0), week 8, week 13, and EOT (week 18) and included clinical evaluations using the Investigator Global Assessment (IGA), Dermatology Life Quality Index (DLQI), Psoriasis Area and Severity Index (PASI), and Target Plaque Severity Score (TPSS). At weeks 8 and 13, IGA and DLQI were significantly reduced compared with baseline, indicating improved disease control and quality of life. However, scores returned to baseline levels at EOT, highlighting the short-term efficacy of NB-UVB. PASI and TPSS were significantly reduced at all visits compared with baseline. Notably, PASI and TPSS for placebo-treated plaques increased from week 8 to EOT, whereas TPSS for Cal/BD treated plaques demonstrated a sustained reduction. Moreover, Cal/BD-treated plaques exhibited significantly lower TPSS than placebo at EOT (p = 0.0429), demonstrating Cal/BD’s longer-lasting effect. To compare TPSS with overall psoriasis severity, unweighted average PASI values across body regions were used, providing a standardized total severity score predominantly reflecting non-topical-treated areas. Cal/BD and placebo-treated plaques showed significantly lower severity than the total severity at weeks 8 and 13. Interestingly, at EOT, only Cal/BD maintained significantly lower severity. In conclusion, combining Cal/BD with NB-UVB effectively reduced disease activity, improved patient outcomes, and enhanced quality of life. Cal/BD demonstrated superior efficacy compared with placebo, underscoring its potential for long-term management. Although NB-UVB can be burdensome due to frequent clinic visits and short-term efficacy, combining it with Cal/BD helps maintain therapeutic effects with a more patient-convenient regimen.
P87 Hitting two targets with one arrow: successful treatment of psoriasiform dermatitis with upadacitinib
Journal: British Journal of Dermatology (2024)

Abstract Psoriasiform dermatitis is a chronic, inflammatory condition that resembles psoriasis and is characterized by scaly, erythematous plaques. It can be challenging to treat as traditional treatments such as topical corticosteroids, phototherapy and systemic agents often fail or present significant side effects. This case study explores the successful treatment of a female patient with psoriasiform dermatitis using upadacitinib, a (JAK1) selective Janus kinase inhibitor. A 52-year-old female, with a 5-year history of psoriasiform dermatitis, histologically proven, presented to the outpatient department of dermatology exhibiting extensive lesions on trunk, back, arms and legs accompanied by severe itching. Anterior treatments, including topical and oral steroids, methotrexate, cyclosporine, narrowband UVB, omalizumab and secukinumab provided minimal relief. Additionally, our patient experienced an important discomfort and a reduced quality of life during all these years due to the persistent nature of her disease. Due to the fact that the ultimate EASI score (Eczema Area and Severity Index) and IGE (Immunoglobulin E) were very high, we decided to initiate upadacitinib in a dosage of 30 mg/day. Our patient reported great improvement in the pruritus within 5 days of receiving upadacitinib. Clinical evaluation marked a significant reduction of scaling and erythema, as well, at Week 4. By the 12th week, the patient achieved complete clearance with no adverse events reported. Furthermore, her emotional well-being and quality of life were improved. This case demonstrates that upadacitinib can be a well-tolerated and rapid treatment option for patients with psoriasiform dermatitis who are refractory to other conventional therapies. Its ability to modulate the immune response may offer a promising therapeutic approach for managing chronic inflammatory skin diseases.
P131 International Benchmarking on Psoriasis Pharmacoepidemiology: Epidemiology, Etiologies, Symptoms, Treatment and Prevention
Journal: British Journal of Dermatology (2024)

Abstract Psoriasis which can involve the skin, nails and joints, is classified by the World Health Organisation as chronic, painful, disfiguring and disabling non communicable disease (NCD) for which there is no specific and definitive cure.1 Why Psoriasis is very difficult to treat? It is like this, because, it looks like many skin diseases at the same time,2 with no specific clinical aspects and many factory interacting together: Environmental, Psychological, Immunological, Genetic and Physiological. As a result, the therapeutic solution will be difficult in most clinical cases and will take time for a definitive recovery. This lead us to prepare an international Benchmarking on Psoriasis Pharmacoepidemiology: Epidemiology, Etiologies, Symptoms, Treatment and Prevention. Despite Of Corticosteroids, which are the best medicine for many diseases all over the world, there are other medicines to use Therefore, scientists have been fighting for so many years, to find new medicines and therapeutic protocols especially natural ones, using herbs and nutritional methods to treat Psoriasis. This study will give us an holistic overview from the theoretical recovery guarentees of varied treatments in different countries worldwide (using Argan oil in Morocco, using Vitamin d in France,...) to the Pratical recovery ­constraints.
P86 Mendelian randomization points to a potential role of OX40 in mediating the effects of smoking initiation on Palmoplantar Pustulosis
Journal: British Journal of Dermatology (2024)

Abstract Palmoplantar pustulosis (PPP) is a rare variant of psoriasis characterized by sterile pustules on the palms and soles. As pathogenic pathways remain poorly understood, no targeted therapeutics are available. Most individuals with PPP are current or past smokers, indicating a likely pathogenic role for cigarette smoking. To explore what pro-inflammatory factors might mediate this relationship, we carried out a two-step Mendelian Randomization analysis. We first examined the influence of smoke on the plasma levels of 160 cytokines and chemokines, using proteome GWAS data generated by the UK biobank. This showed that the levels of 45 plasma proteins were likely to be causally affected by smoking initiation. When these proteins were examined as an exposure in the second step of the analysis, a 1-standard deviation increase in the plasma level of TNFRSF4 (OX40) was predicted to casually influence PPP (Padj = 2.46 × 10−3; odds ratio: 1.50). Consistent results were obtained in sensitivity analyses. As the relatively small size of the PPP GWAS (n = 1456 cases) reduced the power to detect robust associations, a larger dataset will be required to confirm our findings. While our study highlights the difficulty of investigating rare conditions with population-wide methods, it identifies OX40 as an inflammatory protein that could mediate the pathogenic effects of cigarette smoking in PPP.
P37 Humoral immunity to mRNA-based COVID-19 vaccines after a booster dose in patients with psoriasis receiving immunomodulatory therapy
Journal: British Journal of Dermatology (2024)

Abstract Short-term immunity after completing vaccination with mRNA-based COVID-19 vaccines is similar between patients with psoriasis receiving immunomodulatory therapy and healthy individuals. However, a faster decline of immunity 6 months after vaccination in patients receiving immunomodulatory therapy has been described. There is still limited data on long-term immunity to the vaccines and immunity after a booster dose. Here we present data on humoral responses 12 months after the initial vaccine programme and a booster dose in patients with psoriasis receiving MTX or biologics. This study was part of a prospective cohort study that included 123 patients with psoriasis who were receiving immunomodulatory therapy and 226 healthy controls. Humoral immunity to mRNA-based COVID-19 vaccines was measured by IgG level and antibody neutralizing capacity. Blood samples were collected before vaccination, 3 weeks after the first vaccine dose, and 2, 6, and 12 months after the first vaccine dose. All participants received an mRNA-based COVID-19 vaccine and two vaccine doses administrated at the standard interval recommended by the manufacturers. Data were analysed using a mixed effects model with the level of IgG or neutralizing capacity as the dependent variable, time of sampling and participant group as fixed effects, and participant ID as a random effect. At 12 months, data were available for 63 patients receiving the following treatments: anti-tumour necrosis factor-α (n = 24), anti-interleukin (IL)-17 (n = 5), anti-IL-12/23 (n = 16), MTX (n = 18), and 173 healthy controls. A booster vaccine dose was received by 95% of the patients and 94% of the controls before collecting the 12-month sample. Most patients (98%) and controls (98%) had a positive humoral response, a composite outcome of an IgG level and neutralizing capacity above defined thresholds. However, numeric IgG levels and neutralizing capacities were lower in patients than in controls. In patients, the predicted mean of IgG was 8512 AU/mL, 95% confidence interval (CI) 5835–12 418 compared with 15 029 AU/mL, 95% CI 12 130–18 620 in controls (P &amp;lt; 0.001). For neutralizing capacity, the predicted mean was 95% inhibition, 95% CI 89–100 in patients vs. 99% inhibition, 95% CI 97–100 in controls (P &amp;lt; 0.001). Similar, positive humoral responses were found in patients with psoriasis receiving immunomodulatory therapy and control 12 months after the initial vaccine programme and a booster dose. Levels of IgG and neutralizing capacity increased in both groups after receiving the booster vaccine. However, the numeric level of IgG and neutralizing capacity was lower in patients. It is currently unknown if the observed difference has clinical relevance.
FC17 Inducible deletion of Mettl3 in murine keratinocytes induces spontaneous inflammation: a novel model for palmoplantar pustulosis and palmoplantar pustular psoriasis
Journal: British Journal of Dermatology (2024)

Abstract Palmoplantar pustulosis (PPP) and palmoplantar pustular psoriasis (PPPP) are chronic inflammatory skin conditions characterized by the eruption of sterile pustules on the palms and/or soles. Although several animal models have been established for plaque psoriasis, no models currently exist for PPP or PPPP. In this study, we demonstrate that the inducible deletion of METTL3, an m6A RNA methyltransferase, in murine keratinocytes results in spontaneous, sterile skin inflammation localized exclusively to the palms, soles, and tail. Histopathological examination revealed intraepidermal accumulation of neutrophils and the formation of subcorneal pustules. Transcriptomic sequencing showed that the gene expression profile of the tail lesions closely resembles that of psoriatic lesions in human patients. In the palm lesions, differential gene expression analysis identified pathways associated with leukocyte chemotaxis, migration, and inflammatory responses. KEGG enrichment analysis highlighted several relevant signalling pathways, including the IL-17 signalling pathway, cytokine-cytokine receptor interaction, TNF signalling pathway, and NF-kappa B signalling pathway, etc. Importantly, inflammation-related genes such as Il1b, Il6, and Il19, along with neutrophil chemotaxis-related genes (Cxcl1, Cxcl2, Cxcl3, Cxcl5, and Cxcl15) and antimicrobial peptides (S100a7/8/9 and Defb4), exhibited significantly elevated expression levels in our model, correlating with findings in patient PPP lesions. RT-qPCR further validated our transcriptomic results, while immunofluorescence staining revealed a substantial accumulation of neutrophils at the lesion sites. This study provides a valuable model and foundational basis for future research into PPP and PPPP, laying the basis for new investigations in this field.
P122 HPV in individuals with psoriasis: a systematic review
Journal: British Journal of Dermatology (2024)

Abstract Despite the high prevalence of the inflammatory disease psoriasis, its relation to human papillomavirus (HPV) has yet to be elucidated. The aim of this systematic review was to investigate the intricate relationship between psoriasis and HPV and provide a comprehensive understanding of the bidirectional interplay. A systematic review was conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist in Ovid’s Medline and Embase databases in accordance with PRISMA guidelines. Risk of bias was completed using the Joanna Briggs Institute critical appraisal tool. Of 271 non-duplicate articles, 19 studies were included in the review, including 1 case–control study, 6 case reports, 3 case series, 3 cohort studies, 6 experimental studies, and 2 prospective cohort studies. The occurrence of HPV in patients with psoriasis is conflicting, with findings varying from that equal to the general population to significantly greater. HPV infection may trigger psoriasis or treatment of psoriasis, including systemic medications, biologics, and ultraviolet phototherapy may result in HPV via shared pathways of immune dysregulation. The occurrence of HPV in patients with psoriasis may be explained through the numerous shared inflammatory links and pathways between the two diseases and is a point of exploitation for future research and disease management. Limitations of this study include that the risk of bias assessment was variable, and conclusions drawn from case reports are theoretical in basis.
P38 Safety of biosimilars compared with originator adalimumab for psoriasis: a multinational cohort study
Journal: British Journal of Dermatology (2024)

Abstract Adalimumab is a widely used biologic treatment for moderate-to-severe psoriasis. With the expiration of Humira®—the originator adalimumab—patent, adalimumab biosimilars have become available, offering the potential to reduce treatment costs. However, concerns about the safety of biosimilars in clinical practice remain a significant barrier to their widespread adoption for psoriasis treatment. This study aims to compare the safety of adalimumab biosimilars to Humira® for psoriasis in real-world practice. We conducted a prevalent-new user cohort study using data from the French National Health Data System (SNDS), the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR), and the Spanish Registry of Systemic Therapy in Psoriasis (BIOBADADERM). The study compared adalimumab-naive patients (new users) initiating biosimilars with those initiating Humira, and patients who switched from Humira to biosimilars (switchers) with those who continued on Humira. Patients were matched 1:1 based on previous adalimumab exposure time to create equal-sized cohorts of biosimilar and originator users. The primary outcome was serious adverse events (SAEs), defined as any medical events during the use of the study drugs resulting in death or hospitalization. In the result, a total of 7387 biosimilar new users and 3654 switchers were matched and compared respectively with Humira new users and continuous users. The incidence rates of SAEs per patient-year were similar between biosimilar and Humira new users [incidence rate ratio (IRR): 0.91, 95% confidence interval (CI): 0.80–1.05] and between switchers and continuous Humira® users (IRR: 0.92, 95% CI: 0.83–1.01). The time to the first SAE occurrence was significantly lower among biosimilar new users compared with Humira® new users [hazard ratio (HR), 0.83; 95% CI: 0.72–0.96]. However, this difference was observed only in registries where most Humira users were recruited before biosimilars were available, suggesting potential residual confounding from changes over time in practices and prescription trends. The time to the first SAE occurrence was similar between switchers and continuous Humira users (HR: 0.94, 95% CI: 0.85–1.05). In conclusion, adalimumab biosimilars demonstrated a comparable safety profile to Humira for both new users and patients who switched from Humira to biosimilars.