tbuckley/cabot-search huggingface dataset:
P103 Analysis of cumulative life course impairment in tertiary psoriasis care: insights from the initial delivery of the DermCLCI-r questionnaire in an English cohort
Journal: British Journal of Dermatology (2024)

Abstract Chronic diseases such as psoriasis place an ongoing and aggregate burden on patients throughout their life, leading to a negative life-changing impact on decisions and opportunities in patients’ lives. This phenomenon is known as Cumulative Life Course Impairment (CLCI), yet no tools which measure CLCI in a standardized way in patients exist. The DermCLCI-r questionnaire is a novel 25-item questionnaire assessing the impact of psoriasis over the whole course of a patients’ disease journey. This questionnaire is undergoing simultaneous validation in German and English language between centres in Germany and England in a 1-year longitudinal study against existing quality of life tools. This study explores CLCI measured in psoriasis patients from a large tertiary psoriasis clinic in England at the initial assessment with the DermCLCI-r questionnaire and correlates it with clinical and quality of life data. The English data (n = 98) showed 60.2% male; mean age, 51.37 years; mean, 27.98 years since psoriasis diagnosis; mean age of diagnosis, 23.0; mean psoriasis area and severity index (PASI), 3.3; 94% on systemic therapy; 44% PASI &amp;gt; 2; mean DLQI 5.1. 55.1% of patients reported experiencing at least one life-changing experience due to their disease, with a mean number of 4.35 life-changing experiences per patient. The most common life-changing experiences were ‘feeling stressed by the disease’ (31.6%), ‘nervousness, anxiety or tenseness’ (27.6%), ‘impairments regarding choice of clothing’ (26.5%), ‘effort with the treatment of the disease’ (26.5%) and ‘limitations in physical performance’ (25.5%). Ongoing cumulative life stress was experienced by 65.3% of patients, with a mean of 5.53 separate items contributing to their current disease burden. Relevant items in the DermCLCIr tool correlated significantly with total DLQI score, e.g. ‘impairments in quality of life’ (0.568), ‘feeling stressed by the disease’ (0.519), and ‘limitations in physical performance’ (0.492), P &amp;lt; 0.001 respectively. CLCI significantly impacts the majority of patients in tertiary psoriasis care and has contributed to multiple ongoing and life-changing experiences in this patient group; the DermCLCI-r questionnaire is able to identify these. The ability to detect CLCI could allow earlier conservative or therapeutic management of life-changing elements of the psoriasis disease experience, and could potentially reduce the negative personal and social impact of psoriasis. Completion of the longitudinal validation study will further assess the accuracy of the DermCLCI-r questionnaire in aiding clinical decision-making on the holistic management of psoriasis patients.
P108 Immunotherapy of psoriasis in the context of underlying malignant disease: risk–benefit balance?
Journal: British Journal of Dermatology (2024)

Abstract The recently established immunotherapeutic approaches to various malignant tumours have dramatically improved patient survival and tumour responses. Yet, they may result in a number of severe unwanted effects on various organs including the skin, which in fact makes up 20–30% of these side effects. Induction or exacerbation of psoriasis is frequent among these. Interdisciplinary care is needed to efficiently approach both tumour and organ-related side effects. This complex issue may be intensively discussed within local interdisciplinary clinical boards on chronic inflammatory diseases (ICB) and is addressed with this case report. A 67-year-old patient was diagnosed with multifocal metastasing small cell lung cancer (SCLS) of his left upper lung lobe and osseous, hepatic and soft tissue metastases. Radiochemotherapy was initiated with cumulative doses of 34 Gy and four cycles of carboplatin and etoposide as well as atezolizumab (anti-PD-L1), the latter continued for maintenance therapy. After 2 years of treatment, no pathologic lymphnodes nor organ metastases could be found with residual pneumonic condensation in his right lung. After 1 year of immune checkpoint inhibition (ICI) both psoriasis arthritis and skin psoriasis appeared with an initial PASI of 20 and a DLQI of 15 and above. The appropriate treatment within this tumour context was intensively discussed by the local ICB. Four injections of guselkumab were well tolerated, yet without any clinical effect. After 7 months of distinct improvement of both skin and joint symptoms upon bimekizumab, clinical effects waned and the therapy was changed another time to injections of adalimumab. This was well tolerated with slow improvement of skin and joint symptoms. The tumour parameters remained unchanged over time. This case demonstrates the induction of psoriasis and psoriasis arthritis by ICI, the critical risk-benefit balance of immunomodulation for psoriasis in the context of underlying malignant disease and the clinical benefit of interdisciplinary discussion within a board on chronic inflammatory diseases.
P08 Study on the impact of COVID-19 infection in patients with moderate-to-severe plaque psoriasis on biologics: a tertiary centre experience in India
Journal: British Journal of Dermatology (2024)

Abstract Introduction As the world faced COVID-19 pandemic, significant concerns were raised regarding its impact on specific patient groups due to paucity of real-world evidence. Individuals with psoriasis undergoing biologic therapy face heightened vulnerability to severe disease. This study aimed to examine the effects of COVID-19 infection on patients with moderate-to-severe plaque psoriasis treated with biologic agents. Materials and Methods Medical records of patients with moderate-to-severe plaque psoriasis undergoing biologic treatment at a tertiary care centre were retrospectively reviewed from March 2021 to June 2021. Patients with confirmed COVID-19 infection, identified through positive polymerase chain reaction tests, were included. Data on patient demographics, disease characteristics, symptoms, and vaccination status were collected and analysed. Results Among 34 infected patients (26 males, 8 females), median age was 50 years (range: 18–70) with a median psoriatic disease duration of 12 years (range: 12–32). Median psoriasis area and severity index (PASI) was 14, with 22.2% of patients having psoriatic arthritis. Comorbidities included overweight (34.4%), obesity (39.2%), dyslipidaemia (24.4%), diabetes mellitus (11.7%), arterial hypertension (7.0%), and coronary artery disease (2.3%). Most patients experienced mild COVID-19 symptoms; 3 required hospitalization due to dyspnoea and hypoxia. At the time of infection, 80% had received at least one dose of mRNA vaccine. Conclusion Our findings suggest that patients receiving biologic therapy for psoriasis did not exhibit a higher risk of severe COVID-19 outcomes. Also, biologic treatment did not appear to impact disease severity adversely indicating potential benefits such as reduced infection risk and milder symptoms. Continuation of biologic therapy in psoriasis patients, even during the pandemic, is essential for effective disease management. Patient education and counselling regarding hesitancy are equally important in such difficult times.
P67 Prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease and the diagnostic accuracy of non-invasive biomarkers for liver fibrosis in patients with psoriasis
Journal: British Journal of Dermatology (2024)

Abstract Psoriasis has been associated with an increased risk of liver fibrosis. Recent studies indicate that metabolic dysfunction-associated steatotic liver disease (MASLD) might be the underlying cause. Furthermore, no clear consensus exists on how to monitor patients with psoriasis for liver fibrosis. Therefore, we assessed the prevalence of MASLD and examined the diagnostic accuracy of non-invasive biomarkers for liver fibrosis. We included patients with psoriasis from a prospective observational cohort study at a university hospital. The prevalence of MASLD was assessed using Fibroscan with hepatic steatosis defined as a controlled attenuation parameter of &amp;gt;250 dB/m and significant/advanced fibrosis as a median liver stiffness measurement (LSM) ≥8 kPa. Non-invasive biomarkers for fibrosis included, fibrosis-4 index (FIB-4, increased if ≥1.3), N-terminal propeptide of collagen type III (PIIINP, increased if &amp;gt;11.0 µg/L for ≤40 years and &amp;gt;9.5 µg/L for &amp;gt;40 years), and the enhanced liver fibrosis (ELF) test (increased if ≥9.8). Analyses were parametric or non-parametric depending on the distribution of data. We enrolled 403 patients (median age 53 years, 54% men). The mean body mass index was 27.8 (standard deviation ± 6.0). In the self-reported questionnaire, 5% of the patients reported consuming &amp;gt;16 units of alcohol per week, 31% reported having hypertension, 28% dyslipidaemia, and 6% Type 2 diabetes. Most patients (75%) received systemic treatment (conventional or biologics), while 25% only used topicals. The patients were generally well-treated with a median psoriasis area and severity index (PASI) of 2.6 (range, 0–41). Based on the FibroScan, 40% had hepatic steatosis (mean CAP 245, ±55 dB/m). The proportion with possible fibrosis was 5% based on FibroScan (median LSM, 4.9 kPa; range, 1.8–20.6), 24% based on FIB-4 (median, 0.89; range, 0.19–8.11), 20% based on ELF (mean, 9.0, ±0.98), and 14% based on PIIINP (median, 6.9 µg/L; range, 2.3–23.1). Pearson’s correlation coefficient between liver fibrosis and the non-invasive biomarkers was highest for FIB-4 (r = 0.57), with corresponding values of r = 0.40 for ELF and r = 0.30 for PIIINP. Furthermore, with Fibroscan as the gold standard, FIB-4 and ELF had better diagnostic accuracy than PIIINP for diagnosing liver fibrosis with an area under the receiver operating characteristic curve of 0.92 (95% confidence interval, 0.87–0.97) for FIB-4, 0.90 (0.83–0.97) for ELF, and 0.77 (0.66–0.87) for PIIINP. In conclusion, 40% of the patients had liver steatosis and 5% displayed liver fibrosis as determined by Fibroscan. FIB-4 and ELF tests demonstrated superior diagnostic accuracy compared with PIIINP.
P61 Proactive therapeutic drug monitoring versus routine care with the novel biologics in psoriasis: a pragmatic, multicentric, randomized, controlled study: the HELIOS study
Journal: British Journal of Dermatology (2024)

Abstract Introduction &amp; Objectives Psoriasis is a chronic immune-mediated inflammatory skin disease for which treatment with biologics is highly effective. In general, these drugs are prescribed according to a ‘one-dose-fits-all’ principle, which might lead to under- or overdosing, causing suboptimal response and unnecessary high drug exposure, respectively. A tool that may support the rational use of biologics is therapeutic drug monitoring (TDM). TDM is the measurement of blood drug concentrations in order to individualize dosing regimens to achieve maximal clinical efficacy and minimize adverse events. The primary objective of this trial is to assess whether proactive TDM of IL-17 and/or IL-23 inhibitors is non-inferior compared with standard of care (SOC) with respect to sustained disease control in patients with moderate-to-severe psoriasis. Materials &amp; Methods This is a pragmatic, multicentre, individually randomized, controlled non-inferiority trial. A total of 210 patients using secukinumab, ixekizumab or guselkumab for at least 6 months according to the standard dosing scheme, will be randomized (1:1) to TDM or SOC. In the TDM group, dosing intervals will be prolonged or shortened stepwisely. This will happen based on the blood drug concentrations of the biologic, measured every 3 months and in accordance with the decision tree. Disease activity and quality of life will be monitored every 3 months by PASI, IGA, BSA, DLQI-R and SF-36. The primary endpoint is sustained disease control, defined as an absolute PASI ≤2 or a delta PASI from baseline ≥50% for at least 80% of all 3-monthly study visits over a period of 18 months. Secondary outcomes include courses of PASI and DLQI, serious adverse events, health-related quality of life, cost-effectiveness and treatment satisfaction. The outcomes of TDM will be compared with those of SOC. Results Inclusion will start in August 2024. The first preliminary results will be presented at the European Academy of Dermatology and Venereology Congress 2026. Conclusion With this study, we aim to assess whether proactive TDM of IL-17 and IL-23 inhibiting biologics is feasible, safe and cost-effective. Proactive TDM in psoriasis patients may lead to more efficient and rational use of the highly effective—though expensive—biologics.
P133 Evaluation of serum uric acid among the patients with psoriasis
Journal: British Journal of Dermatology (2024)

Abstract Background Psoriasis is a common papulosquamous, chronic inflammatory skin disorder, clinically characterized by sharply demarcated erythematous plaques covered by silvery-white scales preferentially on the extensor surface of upper extremities, knee, scalp, umbilicus and lumbar area. Studies have shown that psoriasis can progress to systemic involvement like psoriatic arthritis, metabolic syndrome, uric acid and lipid metabolism derangement. The aim of this study was to evaluate serum uric acid levels among patients with psoriasis. Method From the outpatient department of the department of Dermatology of Bir Hospital and Shree Birendra Hospital, Chhauni, Kathmandu. One hundred and thirty-eight patients were enrolled in the study. Among them 69 (male = 36 and female = 33) with psoriasis were selected as case, 69 patients with other dermatologic diseases after matching age and sex were selected as controls. Informed written consent, after a detailed history and physical examination, body mass index (BMI) and psoriasis area and severity index (PASI) of cases were calculated and they were sent for serum uric acid investigation. The serum uric acid level was determined for both cases and controls. Results Chronic plaque psoriasis was the most common 60 (87.0%) variant and there was no significant association between psoriasis type and sex. The male–female ratio was 1.09:1. Majority of the psoriasis patients (76%) were among the younger population and most of them (91.3%) had normal serum uric acid levels. Most of the patients 55 (79.7%) did not have a family history of psoriasis. Patients 58 (84.1%) had a history of flare up in the winter season. Body mass index was found to be normal range in most 65 (94.2%) of the patients. Among the control group, eczema was the most common 16 (23%) diagnosis and most of the patients (91.3%) had normal serum uric acid levels. No significant association between psoriasis area severity index score and serum uric acid level was found in the study (P = 0.81). Conclusion In our study, serum uric acid was more significant among psoriasis patients than the control group. Most of the patients had aggravating psoriasis in the winter season. However, it was not also significant with psoriasis area and severity index, this may be due to psoriasis lesions were not severe or extensive body surface area involvement and no systemic complication issues. However, we have to rule out other systemic complications due to psoriasis in long-term follow-up.
P45 GUIDE trial results after withdrawal in Part 3: long-term remission in patients with psoriasis treated with guselkumab within 15 months from onset of symptoms
Journal: British Journal of Dermatology (2024)

Abstract GUIDE is an ongoing Phase 3b, randomized, double-blind trial examining early intervention with guselkumab in moderate-to-severe psoriasis. Super-responder [psoriasis area and severity index (PASI) = 0 at Weeks 20 and 28] patients with PASI &amp;lt; 3 at Week 68 were withdrawn from treatment in Part 3 of GUIDE (Weeks 68–220). Super-responder with short disease duration (SDD, guselkumab initiated ≤2 years from symptom onset) remained treatment-free longer than super-responders with long disease duration (LDD, &amp;gt;2 years; median 378 vs. 259 days). Here, we further investigate the impact of psoriasis disease duration on the median treatment-free period and long-term remission following guselkumab withdrawal in Part 3 of the GUIDE trial. Of 880 patients enrolled, 303 (34.4%) were super-responders; 273 were withdrawn from guselkumab at Week 68 [135 (49.5%) LDD; 138 (50.5%) SDD, thereof 71 (26.0%) had intermediate-SDD (ISDD; 15–24 months disease duration); and 67 (24.5%) had ultra-SDD (USDD, &amp;lt;15 months disease duration) patients]. Following guselkumab withdrawal, 35.5% of SDD and 18.5% of LDD patients remained treatment-free through Week 116 (PASI ≤5 at all visits). Among SDD patients, 43.3% of USDD vs. 28.2% of ISDD patients remained treatment-free through Week 116. Median treatment-free time was 449 days for USDD vs. 291 days for ISDD patients (hazard ratio: 0.39; 95% confidence interval: 0.24–0.62; nominal-P &amp;lt; 0.001). Among patients with clear skin (PASI = 0) at Week 116/Week 128/Week 140, 60.9%/76.5%/76.9% had USDD, 21.7%/17.6%/15.4% had ISDD, and 17.4%/5.9%/7.7% had LDD. After treatment withdrawal, super-responders treated with guselkumab within &amp;lt;15 months from symptom onset had a longer treatment-free time and were more likely to have clear skin than super-responders treated within 15–24 months. Findings suggest that very early intervention with guselkumab may modify disease mechanisms and counter disease progression.
P03 RSAD2 regulated by IRF1 contributes to keratinocyte hyperproliferation and skin inflammation in psoriasis via the TAK1/NF-κB axis
Journal: British Journal of Dermatology (2024)

Abstract Background Radical SAM domain-containing 2 (RSAD2) plays a crucial role in the innate immune response and is associated with a variety of immune diseases. However, the expression and immunomodulatory role of RSAD2 in psoriasis have not been clarified. Objectives We sought to explore the role of RSAD2 in psoriasis and its molecular mechanisms. Methods Western blot, qRT-PCR, immunohistochemistry and immunofluorescence staining were used to detect the expression of RSAD2 in psoriatic lesions. Datasets from the GEO database were analysed to reveal the relationship between the expression of RSAD2 and the severity of psoriasis. RNA-seq analysis was performed to identify genes and pathways regulated by IRF1 or RSAD2. A dual-luciferase reporter assay and CUT&amp;Tag were performed to detect the direct binding of interferon regulatory factor-1 (IRF1) to RSAD2. CCK8, EdU assays, flow cytometry, and ELISA were used to determine the role of RSAD2 in the psoriatic cell model. Western blot was performed to investigate the relationship between RSAD2 and the TAK1-mediated NF-κB signalling pathway. The IMQ-induced psoriasis-like mouse model was established for in vivo experiments. Results RSAD2 was significantly upregulated in psoriatic tissues and in psoriasis-like mouse epidermis, and its expression correlated positively with the severity of psoriasis. In M5-treated keratinocytes, RSAD2 promotes the proliferation and secretion of proinflammatory cytokines by activating TAK1-mediated NF-κB signalling pathway. IRF1 increased the expression of RSAD2 by binding to the RSAD2 promoter region and the function of RSAD2 in psoriasis is regulated by IRF1. Moreover, treatment of RSAD2 siRNA decreased epidermal hyperplasia and attenuated IMQ-induced psoriatic dermatitis. Conclusions Our study revealed that upregulation of RSAD2 contributes to keratinocyte hyperproliferation and skin inflammation in psoriasis and is positively correlated with the severity of psoriasis, and the effect of RSAD2 is regulated by IRF1. RSAD2 may be a potential biomarker and therapeutic target in psoriasis.
P11 Genetics behind the systemic inflammation in psoriasis: functional aspects of NLRP3 polymorphisms
Journal: British Journal of Dermatology (2024)

Abstract The systemic inflammation in psoriasis is thought to underlie the high prevalence of cardiovascular comorbidity, but the underlying mechanisms are poorly understood. The NLRP3 inflammasome is strongly linked to cardiovascular disease (CVD) and is genetically associated with both CVD and psoriasis. In this study, we investigated the association of two single nucleotide polymorphisms (SNPs) in the NLRP3 gene (rs10754555 and rs12239046) with psoriasis. These SNPs are associated with systemic inflammation and rs10754555 is strongly linked with cardiovascular risk and mortality. DNA from 491 families comprising 1988 individuals were genotyped and analysed using a family-based association test. A significant association of rs12239046 [odds ratio (OR): 1.29; P = 0.018] and a marginally significant association of rs10754555 (OR: 1.24; P = 0.054) with psoriasis susceptibility was identified. Further, using flow cytometry, we found that monocytes from individuals heterozygous for rs10754555, express significantly more NLRP3 when stimulated with LPS for 60 min compared with the wild type. SNP rs12239046 did not exhibit this phenomenon. Intriguingly, the psoriasis patients homozygous for the rs10754555 risk allele were on anti-TNFα-treatment, proposing a more severe phenotype. Our results suggest a genetic component contributing to the systemic inflammation in psoriasis patients. This genetic insight could potentially be used to identify psoriasis patients at higher risk of systemic inflammation and cardiovascular complications.
P10 Lipid metabolism modulated by <i>N</i>6-methyladenosine modification governs neutrophil chemotaxis and skin immune homeostasis
Journal: British Journal of Dermatology (2024)

Abstract Disruption of N6-methyladenosine (m6A) modification has been implicated in various inflammatory disorders; however, its role in the regulation of cutaneous inflammation remains poorly understood. In this study, we demonstrate that both m6A and its methyltransferase, METTL3, are significantly downregulated in keratinocytes associated with inflammatory skin diseases such as psoriasis and atopic dermatitis. Inducible deletion of Mettl3 in murine keratinocytes heightened susceptibility to cutaneous inflammatory responses, characterized by enhanced neutrophil recruitment and fatty acid metabolism rewiring. Importantly, we propose a model in which m6A modification stabilizes the mRNA of the lipid-metabolizing enzyme ELOVL6 via the m6A reader IGF2BP3. This stabilization reprogrammes fatty acid metabolism, resulting in decreased palmitic acid accumulation and, consequently, suppression of neutrophil chemotaxis during cutaneous inflammation. Our findings illuminate a previously unrecognized epithelial-intrinsic m6A modification-lipid metabolism axis that is crucial for maintaining epidermal and immune homeostasis, thereby providing a foundation for potential therapeutic strategies targeting m6A modulators to alleviate inflammatory skin disorders, including psoriasis and atopic dermatitis.