tbuckley/cabot-search huggingface dataset:
P121 Distribution and treatment patterns in pustular psoriasis on two continents: insights from the international registry (IRASPEN)
Journal: British Journal of Dermatology (2024)

Abstract Background Pustular psoriasis is a group or rare, neutrophilic conditions including Generalized Pustular Psoriasis (GPP), Palmoplantar Pustulosis (PPP), and Acrodermatitis Continua of Hallopeau (ACH). Each presents unique management challenges. The International Registry of Pustular Psoriasis (IRASPEN) is a prospective 10-year registry that collects a comprehensive real-world dataset to explore patient demographics, clinical features and treatment patterns all over the world. Methods In 9 centres in Europe and Asia, 81 patients were included with diagnoses established according to the ERASPEN criteria. An analysis was conducted on data categorized by diagnosis, age, gender, and location. The study focuses on the distribution of treatments for GPP, PPP, and ACH across Europe and Asia, detailing how these conditions are managed in different regions. Results In this first analysis, baseline cross-sectional data are presented. 46 patients with PPP were included, making up 56% of the cohort. Thirty patients had GPP, and only five patients had ACH. Demographic Distribution The age range spans from 13 to 86 years. There is a female predominance, with 71% (58) of the cohort being female, which may suggest gender-related differences in disease incidence or reporting. Reflecting the number of centres, the majority of patients are from Europe, with 70 individuals from Germany, Italy, Portugal, Switzerland, and Turkey. The Asian cohort includes 11 patients from Singapore and Malaysia. Treatment strategies Of all treatment choices used in PPP, 46% were topical, 37% classic systemic drugs and 17% biological drugs. In GPP, 22% of treatments chosen were topical, 43% classic systemic drugs and 35% biologics. Insight into real-world treatment efficacy was as yet limited as the registry had just started. Conclusion The IRASPEN registry elucidates significant geographical and demographic distinctions in the management of pustular psoriasis. The varied treatment approaches, particularly the heavy reliance on topical agents for PPP and more aggressive treatments for GPP, underscore the necessity for personalized therapeutic strategies. These findings advocate for tailored treatment plans that consider both the type of psoriasis and regional health care practices to optimize patient outcomes.
FC02 Immune cell signatures and T-cell receptor profiling reveal pathogenetic mechanisms in psoriasis
Journal: British Journal of Dermatology (2024)

Abstract Psoriasis is a chronic inflammatory disease with systemic effects and currently has no cure due to an incomplete understanding of its underlying mechanisms. To gain better insights into the immune response associated with psoriasis, we conducted single-cell RNA sequencing and parallel single-cell T-cell receptor (TCR) profiling on peripheral blood mononuclear cells obtained from 11 psoriasis patients and 8 healthy controls. Additionally, we analysed two pairs of skin samples from the psoriasis cohort and performed spatial transcriptomics on two other pairs of skin samples. Our study identified specific immune signatures in myeloid and lymphocyte subsets both in blood and skin and highlighted characteristics of the immune repertoire in psoriasis. Notably, we found an increased proportion of circulating CD14+ monocytes. Furthermore, circulating plasmacytoid dendritic cells in psoriasis patients exhibited heightened expression of genes associated with skin-homing and pro-inflammatory responses. Circulating T cells in these patients showed decreased expression of activation markers. In psoriatic lesions, we observed that resting CD8+ tissue-resident memory T (TRM) cells displayed a gene expression profile similar to that of activated CD8+ TRM cells, though they had lower expression levels of cytotoxicity-related genes. Both resting and activated CD8+ TRM cells in psoriatic lesions showed enhanced interaction strength in terms of signal transmission and reception compared with non-lesions. Activated CD8+ TRM cells were densely infiltrated in the dermis of skin lesions, while resting CD8+ TRM cells were located deeper in the dermis of non-lesion areas. TCR clones that were highly expanded in skin lesions were predominantly CD8+ TRM cells. Distinct TCR clusters showed different gene expression signatures, with one CD8+ TRM cluster expressing IFNγ and another expressing IL-17. These findings provide a valuable resource for further investigation into the pathogenesis of psoriasis by offering insights into the immune cell dynamics within both circulation and local skin environments.
P54 VISIBLE cohort B: guselkumab demonstrates significant scalp clearance at Week 16 in participants with moderate-to-severe scalp psoriasis across all skin tones
Journal: British Journal of Dermatology (2024)

Abstract The ongoing first-of-its-kind, large-scale, prospective, Phase 3b, randomized, double-blind, placebo-controlled VISIBLE study is evaluating the efficacy and safety of guselkumab in participants with moderate-to-severe body or scalp psoriasis across all skin tones. Scalp psoriasis causes physical and social distress (daily life interference) and is often associated with intense pruritus and scaling, and sometimes alopecia. This analysis presents the efficacy and safety of guselkumab vs. placebo from the VISIBLE moderate-to-severe scalp psoriasis cohort at Week (W)16. VISIBLE Cohort B participants (N = 108) received (3:1) guselkumab 100 mg or placebo at W0, W4, then every 8W. Co-primary endpoints: proportions of participants achieving scalp-specific Investigator Global Assessment (ss-IGA) response of absence of disease (0)/very mild disease (1) and Psoriasis Scalp Severity Index (PSSI) 90 response at W16. Major secondary endpoints: proportions of participants achieving complete scalp clearance (ss-IGA 0 and PSSI 100), median time to PSSI 90 response, and mean per cent improvements in PSSI and scalp surface area (SSA). Efficacy analysis included participants correctly randomized to Cohort B (n = 102); safety analysis included all randomized participants (n = 108). Participants were largely male (56.9%) with a median age of 43.5 years and mean baseline weight of 88.1 kg. Despite participants having extensive moderate-to-severe scalp disease (mean SSA: 59.8%, mean PSSI: 34.3; ss-IGA 3: 82.4%; ss-IGA 4: 17.6%), &amp;lt;20% of participants had received prior systemic therapies (11.8%, phototherapy; 17.6%, non-biologic systemics; and 12.7%, biologics). Significantly greater proportions of guselkumab-treated participants achieved the co-primary endpoints vs. placebo: ss-IGA 0/1 (68.4 vs. 11.5%) and PSSI 90 (65.8 vs. 3.8%; both P &amp;lt; 0.001). Median time to PSSI 90 response was 11.6W for the guselkumab group (vs. not achieved by placebo). Significantly greater proportions of guselkumab-treated participants achieved complete scalp clearance vs. placebo (ss-IGA 0: 57.9 vs. 3.8%; PSSI 100: 59.2 vs. 3.8%; both P &amp;lt; 0.001). Significantly greater mean per cent improvements in PSSI (87.6 vs. 37.8%) and SSA (86.6 vs. 33.4%) from baseline were reported with guselkumab vs. placebo groups (both P &amp;lt; 0.001). There were no new safety signals, and safety findings were consistent with the established guselkumab safety profile. After just 3 doses of guselkumab, the majority of participants achieved rapid and significant scalp clearance across all measures evaluated, with nearly 6 of 10 achieving complete scalp clearance at W16. These results highlight that guselkumab is a highly effective treatment for extensive moderate-to-severe scalp psoriasis and will enable evidence-based shared decision-making for people with scalp psoriasis across diverse populations and the full range of skin tones.
Omission of postoperative radiotherapy after breast-conserving surgery in low-risk breast cancer
Authors: Sofia Palmér, Antonis Valachis, Henrik Lindman, Daniel Robert Smith, Åsa Wickberg, Fredrika Killander, Judith Bjöhle, Zakaria Einbeigi, Greger Nilsson, Johan Ahlgren, Kenneth Villman
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background This prospective cohort study aimed to assess whether postoperative radiotherapy could safely be omitted in women ≥ 65 years with low-risk, estrogen receptor (ER)-positive T1N0 breast cancer treated with breast-conserving surgery and adjuvant endocrine therapy. Methods Eligible patients were women ≥ 65 years with unifocal, non-lobular, grade 1 or 2, ER-positive, pT1N0 breast cancer treated with breast-conserving surgery and endocrine therapy for five years. Patients were followed up with mammography at least annually for 10 years. The primary endpoint was local recurrence. Secondary endpoints were contralateral breast cancer, recurrence-free survival, and overall survival. Results The final study cohort included 601 patients with a median age of 71 years (range: 65 to 90 years) and a median tumor size of 11 mm (range: 3 to 20 mm). Median follow-up time was 119 months (interquartile range: 103 to 121 months). The cumulative incidence of local recurrence was 1.5% (95% confidence interval (CI): 0.8 to 2.8%) and 5.5% (95% CI: 3.8 to 7.6%) at 5 and 10 years, respectively. The cumulative incidence of contralateral breast cancer was 1.7% (95% CI: 0.9 to 3.0%) at 5 years and 4.5% (95% CI: 3.0 to 6.6%) at 10 years. The overall survival rate at 10 years was 83.1% (95% CI: 80.8 to 85.4%). In total, three patients (0.5%) died due to breast cancer. Conclusion Our results support the possibility to omit radiotherapy after breast-conserving surgery in a well-defined subgroup of women aged ≥ 65 years with low-risk, ER-positive, pT1N0 breast cancer receiving adjuvant endocrine therapy.
FC23 High induction dosing of risankizumab in patients with moderate-to-severe plaque leads to marked suppression of resident memory T cell number and function in resolved psoriatic skin
Journal: British Journal of Dermatology (2024)

Abstract Risankizumab, a humanized monoclonal antibody that specifically inhibits IL-23, is approved to treat moderate-to-severe plaque psoriasis. In Phase 2, double-blinded, single-centre KNOCKOUT (NCT05283135) study, we evaluated higher-than-approved risankizumab induction doses (300 and 600 mg) for efficacy measures and modulation of lesional resident memory T cells (TRM), cells responsible for psoriasis recurrences. A total of 20 patients were enrolled, and 16 patients completed Week 52. Patients were randomized 1:1 to receive subcutaneous risankizumab 300 or 600 mg at Weeks 0, 4, and 16, with no further dosing. Static Physician’s Global Assessment (sPGA) was monitored throughout the study and reported here with modified non-responder imputation. At Week 16, 94.4% [n = 17, 95% confidence interval, CI (72.7, 99.9)] of all patients achieved sPGA 0/1 and 66.7% [n = 12, 95% CI (41.0, 86.7)] achieved sPGA 0. At Week 52, 36 weeks after the last dose, sPGA 0/1 and sPGA 0 responses were achieved by 61.1% [n = 11, 95% CI (35.7, 82.7)] and 44.4% [n = 8, 95% CI (21.5, 69.2)] of all patients, respectively. We also performed single-cell RNA-sequencing of biopsy samples at baseline and at Week 52 from both dose groups. In lesions of patients receiving the higher dose (600 mg) of risankizumab, the number of CD8+ tissue-resident memory T (TRM) cells was markedly reduced, with more marked suppression of the intercellular communication network between TRM and keratinocytes compared with the lower dose (300 mg) group. A shift towards increased crosstalk between Tregs and TRM, was noted, particularly in the 600 mg dose group. Mechanistically, the IL-23 blockade also impaired the expression of IL15 and IL7 in keratinocytes, which are known survival factors for CD8+ TRM. Furthermore, keratinocyte-derived TNFSF15 (TL1A), a known inflammatory signal for TH17 maintenance, was strongly attenuated in the 600 mg dose group compared with the 300 mg dose group. These findings suggest that the high and prolonged therapeutic clinical responses seen with high induction doses of risankizumab may be explained by the marked suppression of TRM number and function.
P02 Assessment of the magnitude and associated factor of psoriasis at Saint Paul’s Hospital Millennium Medical College among patients attending dermatology clinic, Addis Ababa, Ethiopia
Journal: British Journal of Dermatology (2024)

Abstract Background Psoriasis is a chronic, inflammatory skin disorder resulting from a genetic predisposition combined with environmental triggers characterized by sharply demarcated erythematosus whitish scaly plaques. It may be associated with psoriatic arthritis, metabolic syndrome, and other diseases. The prevalence is ∼2% of the world’s population. Two peaks in the age of onset have been reported: early-onset psoriasis at 20–30 years of age and late-onset psoriasis at 50–60 years of age, which are equal in both sexes. Objectives This study aimed to assess the magnitude and associated factors of psoriasis from October 2021 to June 2022 at Saint Paul’s Hospital Millennium Medical College Addis Ababa. Methods A hospital-based cross-sectional prospective study was conducted from October 2021 to June 2022. A total sample size of 422 patients aged 11 and above years was included in the study. Then, using SPSS version 21.0, the data were entered and analysed. A descriptive analysis was performed to characterize the study participants. Bivariate and multivariable logistic regression was performed to determine the crude and independent predictors of the dependent variable. AORs with 95% confidence intervals (CIs) were used to determine the independent predictors of psoriasis. Statistically, a significant association was considered at a P-value &amp;lt;0.05. Result In this study, the magnitude of psoriasis was found to be 6.01% (95% CI: 11.6, 18.7). Moreover, in the multivariable logistic regression model, educational status AOR (95% CI) was 0.054 (0.01–0.30). The patients’ AOR (95% CI) 34.90 (8.27–147.30) stress history was a significant predictor of psoriasis. Conclusion In this study, 6.01% of patients were found to have psoriasis. Therefore, the findings need to give great attention to strengthening national skin disease prevention and control services and implementing public health policies on the awareness, prevention, and treatment of psoriasis patients to keep care of skin and not neglect disease contact health facility services.
P78 Plaque psoriasis and diabetes mellitus in the context of psychosis
Journal: British Journal of Dermatology (2024)

Abstract Psoriasis is an autoimmune autoinflammatory skin disease which may affect any body area. The disease may be accompanied by metabolic syndrome, which in some cases may manifest itself as frank diabetes mellitus. Psychosis, particularly schizophrenia may also be related to the development of diabetes mellitus. The aim was to describe the case of a patient who developed plaque psoriasis at the age of 32 and diabetes mellitus Type 2 thereafter in the context of schizophrenia. A male patient aged 35 presented with plaque psoriasis. Local measures were applied to treat the disease. The patient had been diagnosed at the age of 20 with psychosis, in this particular case schizophrenia. He was on antipsychotic drug treatment. He did not require hospitalization for his mental health issue. At the age of 37 he was diagnosed with diabetes mellitus Type 2. Metformin was administered. However, the patient developed obesity and diabetes mellitus required combined treatment with metformin and vildagliptin. Plaque psoriasis requires only local measures to be controlled with. The presence of metabolic syndrome in the context of psoriatic disease is well described. However, we present the case of a patient with schizophrenia and diabetes mellitus Type 2 in the context of overt metabolic syndrome. Schizophrenia is also known to be associated with the development of diabetes mellitus Type 2. The development of diabetes mellitus in the context of schizophrenia may be related to genetic reasons. However, in our case, it may be related either to genetic reasons or to environmental pressures, or it may be the exhibition of severe stress which the patient cannot properly handle. Severe stress and the inability to cope with it may be related to the development of an autoimmune disease, such as plaque psoriasis in the context of schizophrenia. The presence of diabetes mellitus Type 2 may be related both to schizophrenia and to the metabolic syndrome described within the context of psoriatic disease.
P126 Psoriasis on black skin: the Nigerian factor, diagnosis, care and treatment
Journal: British Journal of Dermatology (2024)

Abstract Psoriasis is one of commonest skin disorders on black skin: it is a condition in which skin cells build up and form scales it is an auto-immune condition that is inherited from either parents or predominantly connected to the genes. It could be itchy, scaly and could lead to depression if proper medical care is not taken. Psoriasis patients could have other systematic skin infections or allergic reactions. Most could have Asthma, sinusitis and allergic Rhinitis. Mostly unidentified in the Nigerian factor or misdiagnosis could be quite common and mostly associated with spiritual folklore. Data reported on SSBC skin care clinics Kaduna for psoriasis patients from 2017 to 2024 as 64 patients. These cases were identified and treated by a skin care consultant and a Dermatologist. Men are more in number than women but a few children also recorded. The treatment of psoriasis patients is in sessions whether it is hives or less affected of which the weather plays an important role. The northern parts of Nigeria has more psoriasis cases due to Natural predicaments, the disorder remains a rare milder disease overall 80.3% Psoriasis and 13. 2 had family history. The Northern central region of Nigeria has an average, population of psoriasis patients and is most common with fulani’s. The fulani’s or Peuhul speak Fulde and are biracial. This common factor of being biracial, fair skin, normadic in nature contributed more to the prevalence of psoriasis with the Hausa fulani’s. Change of environment, weather and food could also be one of the triggers of psoriasis. The patients in some cases treat themselves without proper treatment. Also some patients believe only in traditional medicine. The essence of finding a dermatologist could be another defeating factor that could lead to other health issues inclusive. Psoriasis medications is a continuous process, one of which is light therapy, multivitamins and good diet. The most important is the dermatologist diagnosis, modalities and medication. 13% (124/11 015) study of the Nigerian population shows male prepoderance: with a male-to-female ratio of 1.34:1 majority in the fourth decade of life. Psoriasis is a family thing extending to generations within the family but may occur differently on each of the family trees. Data are as follows: (i)Psoriasis by wk Jacyk-1981; (ii)Dr Yaya Kaduna State Nigeria 2022 cited; (iii)SSBC skin care and Kaduna 2917–2024; (iv)Psoriasis treatment via integrated Medicine: WSDH Guinea 2023 by Dr Maimuna Sani stores, Kaduna state Nigeria; and (v)Study 19 April 2013.
P26 Analysis of the detectability of the association of polymorphism of genotypes of the GSTP1 gene in patients with psoriasis
Journal: British Journal of Dermatology (2024)

Abstract The search for genetic factors in the development of chronic dermatoses is a priority in medical science. It should be noted that in the development and pathogenesis of psoriasis, along with the main trigger factors, so-called modifier genes are involved, the effect of which is largely determined by environmental factors. Among these genes, of particular interest are the glutathione-S-transferase genes—GST, which are responsible for the biotransformation of chemical, biological agents, drugs, etc. entering the body. Particular attention is paid to the enzyme of the second phase of detoxification, glutathione transferase, a product of the GSTP1 gene. The purpose of our research was to assess the detectability of the association of polymorphism of genotypes of the gene for the second phase detoxification enzyme GSTP1 in patients with psoriasis. Material and research methods Forty-five patients with psoriasis aged 18–49 years were examined. Among them, there were 18 male and 27 female patients. All patients underwent clinical, molecular genetic and statistical studies. The control group consisted of 64 healthy individuals of the corresponding age. Research results Analysis of molecular genetic studies of the frequency distribution of the association of polymorphism of genotypes IIe 105 Val of the xenobiotic enzyme GSTP1 gene showed an increased frequency of detection of the heterozygous variant—in 44.4% (20/45) of cases, while in the control group of healthy individuals, it was 10.9% (7/64) respectively. [χ2 = 21.78, P &amp;lt; 0.0003; odds ratio (OR) = 6.51; 95% confidence interval (CI) 2.44–17.375]. The mutant homozygous variant of the IIe 105 Val polymorphism of the GSTP1 gene was detected in 6.6% of cases (3/45), respectively (χ2 = 21.78, P &amp;lt; 0.0003; OR = 10.62; 95% CI 0.54–210.93). Conclusion The results of molecular genetic studies showed that allelic variant G and hetero/homozygous genotypes of the IIe 105 Val polymorphism of the GSTP1 gene are significant markers of an increased risk of developing severe forms of psoriasis in Uzbekistan (P &amp;lt; 0.05) (χ2 = 22.56, P &amp;lt; 0.0002; OR = 7.02; 95% CI 2.89–17.06). The functionally favourable genotype A/A of the GSTP1 gene is a reliable protective marker against the development of pathology (χ2 = 21.78, P &amp;lt; 0.0003; OR = 0.12; 95% CI 0.04–0.31).