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Background Inhibitors of epidermal growth factor receptor (EGFRi) or mitogen-activated kinase (MEKi) induce a folliculitis in 75–90% of patients, the pathobiology of which remains insufficiently understood. Objectives To characterize changes in the skin immune status and global transcriptional profile of patients treated with EGFRi; to investigate whether EGFRi affects the hair follicle's (HF) immune privilege (IP); and to identify early proinflammatory signals induced by EGFRi/MEKi in human scalp HFs ex vivo. Methods Scalp biopsies were taken from patients exhibiting folliculitis treated long term with EGFRi ('chronic EGFRi' group, n = 9) vs. healthy scalp skin (n = 9) and patients prior to commencing EGFRi treatment and after 2 weeks of EGFRi therapy ('acute EGFRi' group, n = 5). Healthy organ-cultured scalp HFs were exposed to an EGFRi (erlotinib, n = 5) or a MEKi (cobimetinib, n = 5). Samples were assessed by quantitative immunohistomorphometry, RNA sequencing (RNAseq) and in situ hybridization. Results The 'chronic EGFRi' group showed CD8+ T-cell infiltration of the bulge alongside a partial collapse of the HF's IP, evidenced by upregulated major histocompatibility complex (MHC) class I, β2-microglobulin (B2 M) and MHC class II, and decreased transforming growth factor-β1 protein expression. Healthy HFs treated with EGFRi/MEKi ex vivo also showed partial HF IP collapse and increased transcription of human leucocyte antigen (HLA)-A, HLA-DR and B2 M transcripts. RNAseq analysis showed increased transcription of chemokines (CXCL1, CXCL13, CCL18, CCL3, CCL7) and interleukin (IL)-26 in biopsies from the 'chronic EGFRi' cohort, as well as increased IL-33 and decreased IL-37 expression in HF biopsies from the 'acute EGFRi' group and in organ-cultured HFs. Conclusions The data show that EGFRi/MEKi compromise the physiological IP of human scalp HFs and suggest that future clinical management of EGFRi/MEKi-induced folliculitis requires HF IP protection and inhibition of IL-33. [ABSTRACT FROM AUTHOR]

Background Sex hormone changes during menopausal transition contribute to declining skin health. However, how menopause and its treatment by hormone replacement therapy (HRT) impact the skin barrier and immune system is unclear. Objectives To examine how menopause and HRT affect the skin barrier and immune cell composition in postmenopausal women following irritant challenge. Methods Two cohorts of postmenopausal women were recruited to the study. The first cohort consisted of 10 untreated women [HRT–; mean (SEM) age 56.5 (1.6) years (range 48–63)] and the second was composed of 8 women receiving HRT [HRT+; mean (SEM) age 54.0 (2.1) years (range 48–63)]. Skin irritation was induced by applying topical sodium lauryl sulfate (SLS) 1.25% to occluded buttock skin for 48 h. Clinical assessment was conducted after 24 h, followed by biopsy of both SLS-challenged and unchallenged skin for analysis of skin barrier proteins and immune cell distribution using immunofluorescence. Results Clinically, there were no significant differences in skin irritant responses between those taking or not taking HRT (including increased skin redness and blood flow). In response to SLS challenge a significant increase in transepidermal water loss (P < 0.05), filaggrin deposition and cytokeratin 10 (K10)+ cell layers (P < 0.01) was observed in individuals receiving HRT compared with the HRT– group. Following SLS challenge in individuals taking HRT, a significant (P < 0.01) reduction in CD207+ cells in the epidermis was observed, accompanied by an increase of CD207+ cells in the dermis, indicative of migrating Langerhans cells (LCs). Significantly fewer migrating LCs were found in those who were not receiving HRT (P < 0.01). Furthermore, the numbers of dermal dendritic cells (DCs), macrophages, and CD11c+CD206– and CD68+CD206– subsets were found to be significantly (P < 0.05) higher in those taking HRT following SLS challenge. Conclusions Individuals receiving HRT displayed enhanced skin barrier response to SLS challenge with thicker filaggrin and increased K10+ epidermal cell layers. Following challenge, HRT users exhibited elevated LC, inflammatory DC and macrophage counts in the dermis. These may render skin both more prone to inflammation and more capable of resolving it, while also promoting skin repair. [ABSTRACT FROM AUTHOR]

This article discusses the prevalence of atopic dermatitis (AD) and psoriasis among indigenous people in Brazil. The researchers accessed a Brazilian national database to gather information on AD and psoriasis diagnoses between 2010 and 2022. They found varying rates of AD and psoriasis across different regions of Brazil. The study highlights the importance of understanding the epidemiology of these skin conditions in indigenous populations for effective healthcare planning and interventions. The study found that the prevalence of AD and psoriasis is lower among indigenous populations compared to urban populations, particularly in remote regions like the Yanomami territory. However, it is important to note that AD and psoriasis can still occur in indigenous communities, especially those located near or within urban areas. [Extracted from the article]

Background Generalized pustular psoriasis (GPP) and palmoplantar pustulosis (PPP) are chronic inflammatory skin conditions. Accumulating evidence shows that GPP and PPP have different characteristics to plaque psoriasis and are distinct clinical entities. Objectives To assess the epidemiology, comorbidities, mortality and healthcare use for patients in England with GPP and PPP versus those with plaque psoriasis. Methods We carried out a cohort study involving analyses of longitudinal electronic health record data in the Clinical Practice Research Datalink Aurum database and linked hospital and mortality data between 2008 and 2019. The primary study outcome was the incidence and prevalence rates of GPP, PPP and plaque psoriasis in England. Secondary outcomes included survival rates and healthcare resource use (HCRU) by disease type. Results We identified 373 patients with GPP, 1828 with PPP and 224 223 with plaque psoriasis. Mean (SD) age was 55.9 (18.6) years for patients with GPP, 51.5 (16.4) years for those with PPP and 48.5 (19.1) years for those with plaque psoriasis; 62.5% and 65.9% of patients with GPP and PPP, respectively, were women, vs. 49.4% of those with plaque psoriasis. About half of patients were overweight or obese at baseline (GPP 48.6%, PPP 56.0%, plaque psoriasis 45.9%). The incidence rates for GPP, PPP and plaque psoriasis were 0.25 [95% confidence interval (CI) 0.21–0.28], 2.01 (95% CI 1.92–2.11) and 103.2 (95% CI 102.5–103.9) per 100 000 person-years, respectively. From 2008 to 2019, the prevalence rates per 100 000 persons ranged from 1.61 to 3.0 for GPP, from 1.1 to 18.7 for PPP and from 1771.0 to 1903.8 for plaque psoriasis. Survival rates were lower for patients with GPP, particularly those who were > 55 years of age and those with a history of one or more comorbidities in each cohort. HCRU was lower in the cohort with plaque psoriasis and highest in the cohort with GPP, particularly among those who had more than one GPP flare. Conclusions Our results provide further evidence that, in England, GPP is a distinct disease with different epidemiology, lower survival and higher HCRU than plaque psoriasis. [ABSTRACT FROM AUTHOR]

A study conducted at a hospital in Kabul, Afghanistan examined the prevalence of anxiety and depression symptoms among patients with psoriasis. The study included 340 individuals, with 57.1% being women and 42.9% being men, and the average age was 35.2 years. The study found that 25.9% of patients had moderate to severe anxiety symptoms, with factors such as being female, older age, low education, and multiple psoriasis symptoms being associated with these symptoms. The study also found that 31.8% of patients had moderate to severe depression symptoms, with similar factors being associated with these symptoms. The study highlights the psychological impact of psoriasis in Afghanistan and suggests the need for screening and integrated management of both dermatological and psychological factors. However, the study's limitations include its single-center, hospital-based nature. [Extracted from the article]

Background Few studies have used real-world data to investigate the association between biologic therapy survival and age at psoriasis onset or HLA-C*06:02 status in patients with moderate-to-severe psoriasis. The robustness of these studies is limited by small sample size, short follow-up and diverse safety and effectiveness measures. Objectives To describe biologic survival and explore whether the response to biologics is modified by age at psoriasis onset or HLA-C*06:02 status in patients with moderate-to-severe psoriasis. Methods Data from patients in the UK and the Republic of Ireland registered in the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) from 2007 to 2022 on a first course of adalimumab, etanercept, secukinumab or ustekinumab with at least 6 months' follow-up and a subset of BADBIR patients with available HLA-C*06:02 information registered to Biomarkers and Stratification To Optimise outcomes in Psoriasis (BSTOP) were analysed. Patients aged ≥ 50 years at treatment initiation were classified into early-onset psoriasis (EOP) (presenting in patients ≤ 40 years of age) and late-onset psoriasis (LOP) (presenting in patients > 40 years of age). BADBIR patients with available information in BSTOP were categorized as HLA-C*06:02− or HLA-C*06:02 +. Biologic survival was defined as treatment discontinuation associated with ineffectiveness or occurrence of adverse events (AEs). Adjusted survival function and hazard ratio (aHR) with 95% confidence interval (CI) were estimated using a flexible parametric model to compare discontinuing therapy between age at psoriasis onset and HLA-C*06:02 groups. Each model included exposure (biologics), effect modifier (age at onset or HLA-C*06:02 status), interaction terms and several baseline demographic, clinical and disease severity covariates. Results Final analytical cohorts included 4250 patients in the age at psoriasis onset group [2929 EOP (69%) vs. 1321 LOP (31%)] and 3094 patients in the HLA-C*06:02 status group [1603 HLA-C*06:02+ (52%) vs. 1491 HLA-C*06:02− (48%)]. There was no significant difference between EOP and LOP in drug survival associated with ineffectiveness or AEs for any biologics. However, compared with patients who were HLA-C*06:02−, patients who were HLA-C*06:02 + were less likely to discontinue ustekinumab for reasons associated with ineffectiveness (aHR 0.56, 95% CI 0.42–0.75). Conclusions HLA-C*06:02, but not age at psoriasis onset, is a predictive biomarker for biologic survival in patients with psoriasis. Findings from this large cohort provide further, important information to aid clinicians using biologic therapies to manage patients with psoriasis. [ABSTRACT FROM AUTHOR]

This document is a supplementary information section of a study conducted by the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR). The study aimed to investigate the factors associated with super responders (SRs) and super nonresponders (SNRs) to biologic therapies in patients with psoriasis. The study found that female sex, shorter study follow-up, higher Dermatology Life Quality Index (DLQI), high frequency of adalimumab, lower frequency of ustekinumab at registration, and higher number of comorbidities were associated with SNRs compared with SRs. The study also mentioned that genetic factors, socioeconomic status, lifestyle factors, adherence to medication, immunogenicity, microbiome, epigenetics, and serum drug levels may play a role in determining treatment response. [Extracted from the article]

Psoriasis causes detriment in a person's physical, mental and social health which impairs their quality of life (QoL). However, the current psoriasis management may not adequately address all relevant health domains. Since the goal of healthcare is to restore or maintain health, health outcomes should include all areas of the patient's overall health. Life satisfaction, QoL and patient well‐being are essential to a comprehensive approach to the disease. With the inclusion of more people‐centred policies, care of patients with psoriasis should evolve towards a holistic and integrated assessment of the disease impact, including subjective measures of well‐being in order to encompass all aspects of health. The main objective of this expert review is to give the concept of well‐being a place as an entity within the holistic therapeutic approach for patients with psoriasis. Identifying and defining common goals beyond the skin with the patient and testing them throughout the course of treatment will benefit and enhance treatment success. We propose a series of recommendations for application in clinical practice, providing tangible clinical guidance for implementing well‐being in the management of psoriasis. Among the recommendations are the need to initially listen to the patient, to know their level of empowerment or what they want to achieve, their preferences in decision making, the evaluation of not only the physical but also the emotional impact of the disease (well‐being), the definition of the aspects that can generate a cumulative deterioration of the disease throughout life, and a continuous assessment of the patient's preferences with the opinion of the expert clinician and the integration of the knowledge of external clinical evidence. [ABSTRACT FROM AUTHOR]

Background: The risks of serious infections that lead to hospitalization and mortality in patients with psoriasis in Asia have not been comprehensively studied. Objectives: We examined the incidence of serious infection and infection mortality in patients with psoriasis. Methods: This population‐based retrospective cohort study used the Taiwan National Health Insurance claims database from 2000 to 2017. Adult patients with psoriasis were identified by a relevant International Classification of Diseases (ICD) code and matched to six comparators without psoriasis on age and sex. Psoriasis patients were categorized as having moderate‐to‐severe disease once exposed to systemic therapies, phototherapy or biologic therapies. The incidence of serious infection and infection mortality were identified by ICD codes from inpatient hospitalization and death registration. Cox proportional hazard models were used to compare the risk, and the results were adjusted for covariates and presented as adjusted hazard ratios (aHR) and 95% confidence interval (95% CI). Results: Overall, 185,434 psoriasis patients and 1,112,581 comparators were included. A higher rate of serious infection (aHR: 1.21, 95% CI: 1.19–1.22) was found in patients with psoriasis compared to matched comparators without psoriasis, and the risk was enhanced when patients had moderate‐to‐severe psoriasis (aHR: 1.30, 95% CI: 1.27–1.34). Specifically, there was an increased risk of serious infection due to respiratory infections (aHR: 1.11, 95% CI: 1.09–1.13), skin/soft‐tissue infections (aHR: 1.57, 95% CI: 1.52–1.62), sepsis (aHR: 1.23, 95% CI: 1.19–1.27), urinary tract infections (aHR: 1.11, 95% CI: 1.08–1.14), hepatitis B (aHR: 1.18, 95% CI: 1.06–1.30) and hepatitis C (aHR: 1.49, 95% CI: 1.32–1.69). Furthermore, psoriasis patients were associated with a higher risk of infection‐related mortality (aHR: 1.15, 95% CI: 1.11–1.18) compared to matched comparators. Conclusion: Patients with psoriasis had a higher risk of serious infection and infection mortality, which was enhanced by moderate‐to‐severe psoriasis. Practitioners should be aware of the increased risk in patients with psoriasis, but it should not be a barrier to offering effective treatment. [ABSTRACT FROM AUTHOR]

Background There is limited understanding of the epidemiology of generalized pustular psoriasis (GPP) internationally, with no population-based estimates of GPP in South East Asia. Objectives To determine the incidence and prevalence of GPP in the Malaysian population and characterize its flares and trigger factors. Methods We conducted a population-based cohort study using the Teleprimary Care database between January 2010 and December 2020. We identified 230 dermatologist-confirmed GPP cases using International Classification of Diseases, 10th revision, diagnostic codes. Annual prevalence and incidence rates were stratified by age, sex and ethnicity. We compared data regarding flares and trigger factors for patients with GPP who had associated psoriasis vulgaris (PV) with those who did not have associated PV. Results The prevalence of GPP was 198 per million (267 women, 127 men) and incidence was 27.2 per million person-years [95% confidence interval (CI) 22.8–31.6]; 35.3 (28.4–42.2) per million person-years for women and 18.3 (13.1–23.5) per million person-years for men. Rates were higher in Chinese individuals [prevalence 271 per million; incidence 41.6 per million person-years (28.9–54.3)] than in the Malay population [prevalence 186; incidence 24.6 (19.4–29.7)] or the Indian ethnic group [prevalence 179; incidence 25.0 (13.8–36.3)]. Annual prevalence was consistently higher in women than in men and highest among the Chinese population, followed by the Indian and Malay populations. Overall, 67% of patients with GPP had associated PV. The prevalence and incidence of GPP without PV were lower than GPP with PV at 66 vs. 132 per million and 19.3 (95% CI 15.6–23.0) vs. 8.0 (95% CI 5.6–10.3) per million person-years, respectively. The mean age at GPP onset was 42.7 years (SD 18.4). A bimodal trend in the age of GPP onset was observed, with first and second peaks at age 20–29 years and age 50–59 years, respectively. Disease onset was significantly earlier in patients with GPP without PV than in those with PV [mean age 37.5 years (SD 20.7) vs. 44.9 years (SD 17.0), P = 0.026]. Flares occurred more frequently in patients without PV than in those with PV [mean number of flares per patient per year was 1.35 (SD 0.77) vs. 1.25 (SD 0.58), P = 0.039]. Common triggers of flares in patients with GPP who did not have PV were infections, pregnancy, menstruation and stress, whereas withdrawal of therapy, particularly systemic corticosteroids, was a more frequent trigger in patients with GPP who also had PV. Conclusions Our findings contribute to the global mapping of GPP, which will help inform the management of this rare condition. [ABSTRACT FROM AUTHOR]

Background Most information on the comparative effectiveness and survival of methotrexate (MTX) and adalimumab (ADA) in the treatment of psoriasis is from randomized control trials and may not translate to the everyday clinical setting. Objectives To determine the real-world effectiveness and survival of MTX and ADA in patients with moderate-to-severe psoriasis registered in the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR). Methods Eligible patients were registered in BADBIR, ≥ 16 years of age and receiving a first course of MTX or ADA between September 2007 and December 2021, with ≥ 6 months of follow-up. Effectiveness was defined as achieving an absolute Psoriasis Area and Severity Index (PASI) ≤ 2 reported ≥ 13 weeks after the treatment start date until the stop date. The average treatment effect (ATE) was estimated using inverse probability of treatment weighting with propensity score, including baseline covariates. ATE results were presented as risk ratios (RR). A flexible parametric model was used to estimate adjusted standardized average survival, defined as treatment discontinuation associated with ineffectiveness or the occurrence of adverse events (AEs) at 6, 12 and 24 months. Restricted mean survival time (RMST) at 2 years of treatment exposure was calculated. Results In total, 6575 patients (median age 44 years; 44% female) were analysed; 2659 (40.4%) were prescribed MTX and 3916 (59.5%) ADA. The proportion of patients achieving PASI ≤ 2 was higher in the ADA cohort (77.4%) than in the MTX cohort (37.4%). ADA was more effective than MTX [RR 2.20, 95% confidence interval (CI) 1.98–2.45]. Overall survival associated with ineffectiveness or AEs was lower in the MTX cohort than in the ADA cohort at 6 months [survival estimate 69.7 (95% CI 67.9–71.5) vs. 90.6 (95% CI 89.8–91.4)], 1 year [survival estimate 52.5 (95% CI 50.4–54.8) vs. 80.6 (95% CI 79.5–81.8)] and 2 years [survival estimate 34.8 (95% CI 32.5–37.2) vs. 68.6 (95% CI 67.2–70.0)]. The difference in RMST (years) overall, or when stratified by ineffectiveness and AEs, was 0.53 (95% CI 0.49–0.58), 0.37 (95% CI 0.33–0.42) and 0.29 (95% CI 0.25–0.33), respectively. Conclusions Patients on ADA were twice as likely to be clear or nearly clear of psoriasis and were less likely to discontinue their medication than patients on MTX. Findings from this real-world cohort provide important information to aid clinicians managing patients with psoriasis. [ABSTRACT FROM AUTHOR]