Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials.

BACKGROUND: Many patients with chronic spontaneous urticaria (CSU) do not achieve complete control of their symptoms with current available treatments. In a dose-finding phase 2b study, ligelizumab improved urticaria symptoms in patients with H1-antihistamine (H1-AH) refractory CSU. Here, we report the efficacy and safety outcomes from two ligelizumab phase 3 studies. METHODS: PEARL-1 and PEARL-2 were identically designed randomised, double-blind, active-controlled and placebo-controlled parallel-group studies. Patients aged 12 years or older with moderate-to-severe H1-AH refractory CSU were recruited from 347 sites in 46 countries and randomly allocated in a 3:3:3:1 ratio via Interactive Response Technology to 72 mg ligelizumab, 120 mg ligelizumab, 300 mg omalizumab, or placebo, dosed every 4 weeks, for 52 weeks. Patients allocated to placebo received 120 mg ligelizumab from week 24. The primary endpoint was change-from-baseline (CFB) in weekly Urticaria Activity Score (UAS7) at week 12, and was analysed in all eligible adult patients according to the treatment assigned at random allocation. Safety was assessed throughout the study in all patients who received at least one dose of the study drug. The studies were registered with ClinicalTrials.gov, NCT03580369 (PEARL-1) and NCT03580356 (PEARL-2). Both trials are now complete. FINDINGS: Between Oct 17, 2018, and Oct 26, 2021, 2057 adult patients were randomly allocated across both studies (72 mg ligelizumab n=614; 120 mg ligelizumab n=616; 300 mg omalizumab n=618, and placebo n=209). A total of 1480 (72%) of 2057 were female, and 577 (28%) of 2057 were male. Mean UAS7 at baseline across study groups ranged from 29·37 to 31·10. At week 12, estimated treatment differences in mean CFB-UAS7 were as follows: for 72 mg ligelizumab versus placebo, -8·0 (95% CI -10·6 to -5·4; PEARL-1), -10·0 (-12·6 to -7·4; PEARL-2); 72 mg ligelizumab versus omalizumab 0·7 (-1·2 to 2·5; PEARL-1), 0·4 (-1·4 to 2·2; PEARL-2); 120 mg ligelizumab versus placebo -8·0 (-10·5 to -5·4; PEARL-1), -11·1 (-13·7 to -8·5; PEARL-2); 120 mg ligelizumab versus omalizumab 0·7 (-1·1 to 2·5; PEARL-1), -0·7 (-2·5 to 1·1; PEARL-2). Both doses of ligelizumab were superior to placebo (p<0·0001), but not to omalizumab, in both studies. No new safety signals were identified for ligelizumab or omalizumab. INTERPRETATION: In the phase 3 PEARL studies, ligelizumab demonstrated superior efficacy versus placebo but not versus omalizumab. The safety profile of ligelizumab was consistent with previous studies. FUNDING: Novartis Pharma.

A partial loss-of-function variant in STAT6 protects against T2 asthma.

BACKGROUND: Signal Transducer and Activator of Transcription 6 (STAT6) is central to Type 2 (T2) inflammation and common non-coding variants at the STAT6 locus associate with various T2 inflammatory traits, including diseases, and its pathway is widely targeted in asthma treatment. OBJECTIVE: To test the association of a rare missense variant in STAT6, p.L406P, with T2 inflammatory traits, including the risk of asthma and allergic diseases, and to characterize its functional consequences in cell culture. METHODS: We tested association of p.L406P with plasma protein levels, white blood cell counts and the risk of asthma and allergic phenotypes. We tested significant associations in other cohorts using a burden test. The effects of p.L406P on STAT6 protein function were examined in cell lines and by comparing CD4+ T-cell responses from carriers and non-carriers of the variant. RESULTS: p.L406P associated with reduced plasma levels of STAT6 and IgE as well as with lower eosinophil and basophil counts in blood. It also protected against asthma, mostly driven by severe T2 high asthma. We showed that p.L406P led to lower IL-4-induced activation in luciferase reporter assays and lower levels of STAT6 in CD4+ T cells. We identified multiple genes with expression that was affected by the p.L406P genotype upon IL-4 treatment of CD4+ T cells; the effect was consistent with a weaker IL-4 response in carriers than non-carriers of p.L406P. CONCLUSIONS: We report a partial loss-of-function variant in STAT6, resulting in dampened IL-4 responses and protection from T2 high asthma, implicating STAT6 as an attractive therapeutic target.

Increased loss-of-function filaggrin gene mutation prevalence in atopic dermatitis patients across northern latitudes indicates genetic fitness: A systematic review and meta-analysis.

Loss-of-function (LoF) mutations in the filaggrin gene (FLG) constitute the strongest genetic risk for atopic dermatitis (AD). A latitude-dependent difference in the prevalence of LoF FLG mutations was systematically evaluated. A systematic review and meta-analysis were performed to estimate the prevalence of LoF FLG mutations in AD patients and the general population by geography and ethnicity. Risk of bias was assessed by Newcastle-Ottawa Scale and Jadad score. StatsDirect, version 3 software was used to calculate all outcomes. PubMed and EMBASE were searched until 9th December 2021. Studies were included if they contained data on the prevalence of LoF FLG mutations in AD patients or from the general population or associations between AD and LoF FLG mutations and were authored in English. Overall, 248 studies and 229 310 AD patients and individuals of the general population were included in the quantitative analysis. The prevalence of LoF FLG mutations was 19.1% (95% CI, 17.3-21.0) in AD patients and 5.8% (95% CI, 5.3-6.2) in the general population. There was a significant positive association between AD and LoF FLG mutations in all latitudes in the Northern hemisphere, but not in all ethnicities. The prevalence of LoF FLG mutations became gradually more prevalent in populations residing farther north of the Equator but was negligible in Middle Easterners and absent in most African populations. FLG LoF mutations are common and tend to increase with northern latitude, suggesting potential clinical implications for future AD management. The existence of possible genetic fitness from FLG LoF mutations remains unknown.

Increasing prevalence of galactose-α-1,3-galactose sensitization in the Danish general adult population.

BACKGROUND: Alpha-gal syndrome is a novel food allergy to the oligosaccharide galactose-α-1,3-galactose (alpha-gal) present in mammalian meat. Tick bites are considered an important route of sensitization to alpha-gal. Data on alpha-gal sensitization in the general population is scant. We utilized a unique data source of repeated population-based health examination studies to assess prevalence, time trends, risk factors, and characteristics of alpha-gal sensitization. METHODS: Alpha-gal sensitization was assessed in >11.000 adults from four health examination studies of randomly invited residents in the Copenhagen region conducted in 1990-1991, 2011-2012, 2012-2015, and 2016-2017. Alpha-gal sensitization was defined as serum specific IgE (sIgE) to alpha-gal ≥0.1 kUA/L; ≥0.35 kUA/L; ≥0.7 kUA/L; ≥3.5 kUA/L. The population was characterized according to genetically determined ABO blood group, aeroallergen sensitization, and pets at home. RESULTS: The prevalence of sIgE to alpha-gal ≥0.1 kUA/L was 1.3% in 1990-1991, 3.7% in 2012-2015 and 3.2% in 2016-2017. Of those sensitized to alpha-gal >97% reported to consume red meat at least once a week, even for sIgE to alpha-gal ≥3.5 kUA/L. Male sex, older age, aeroallergen sensitization, cat at home, and blood group A were associated with increased odds of alpha-gal sensitization. The known protective effect of blood group B was confirmed. CONCLUSION: In this general adult population, the prevalence of alpha-gal sensitization had doubled from 1990-1991 to 2016-2017. This could potentially be due to increased tick exposure and an increased atopic predisposition.

Validity, reliability and responsiveness of digital visual analogue scales for chronic spontaneous urticaria monitoring: A CRUSE® mobile health study.

BACKGROUND: CRUSE® is an app that allows patients with chronic spontaneous urticaria (CSU) to monitor their daily disease activity through the use of visual analogue scales (VASs). We aimed to determine the concurrent validity, reliability, responsiveness and minimal important difference (MID) of CRUSE® VASs. METHODS: We evaluated the properties of three daily VASs: VAS for how much patients were affected by their CSU ('VAS urticaria'), VAS for the impact of urticaria on work/school productivity ('VAS productivity') and the VAS of EQ-5D. Concurrent validity was assessed by measuring the association between each VAS and the Urticaria Activity Score (UAS). Intra-rater reliability was determined based on the data of users providing multiple daily questionnaires within the same day. Test-retest reliability and responsiveness (ability to change), respectively, were tested in clinically stable and clinically unstable users. MIDs were determined using distribution-based methods. RESULTS: We included 5938 patients (67,380 days). Concurrent validity was high, with VAS urticaria being more strongly associated with the UAS score than the remaining VASs. Intra-rater reliability was also high, with intraclass correlation coefficients (ICC) being above 0.950 for all VASs. Moderate-high test-retest reliability and responsiveness were observed, with reliability ICC being highest for VAS EQ-5D and responsiveness being highest for VAS urticaria. The MID for VAS urticaria was 17 (out of 100) units, compared to 15 units for VAS productivity and 11 units for VAS EQ-5D. CONCLUSION: Daily VASs for CSU available in the CRUSE® app display high concurrent validity and intra-rater reliability and moderate-high test-retest reliability and responsiveness.

Prevalence and characteristics of pain in patients with lower-extremity ulcers-A cross-sectional study.

The study aimed to investigate the prevalence and characteristics of pain in different ulcer types and to identify factors associated with pain experience in patients with lower-extremity ulcers. A cross-sectional single-centre study was performed, including 130 newly referred outpatients with lower-extremity ulcers. Pain intensity was measured with a visual analog scale (VAS) and pain characteristics with the short form mcgill pain questionnaire-2 (SF-MPQ-2). The mean pain intensity was 29.5 (SD 31.8) at rest and 35.5 (SD 34.1) during movement (0-100 VAS). 61.5% of the patients experienced pain (VAS > 0) at rest and 70.8% during movement. Moderate to severe pain at rest was seen in 39.2% and in 43.8% of patients during movement. The mean total score on SF-MPQ-2 (range 0-220) was 35.9 (SD 32.6). Most of the patients described pain as intermittent (mean 11.8 SD 13.9). Analgesics were prescribed for 78% of the patients. Ulcer type (i.e., arterial, immunological, pressure and venous) and age were associated with pain severity, and women had a significantly lower well-being score than men. Prevalence of pain in patients with lower-extremity ulcers was high across different ulcer aetiologies. Pain intensity and quality must be assessed to obtain adequate pain management.

Characteristics and drivers of fatigue in patients with psoriasis and psoriatic arthritis: A cross sectional study.

BACKGROUND: A multitude of factors may influence fatigue in psoriasis and psoriatic arthritis (PsA); however, their individual fatigue components have not been thoroughly examined. OBJECTIVES: To explore characteristics of fatigue and its potential drivers in a cohort of patients with psoriasis with or without PsA. METHODS: Adults with psoriasis and a nonpsoriasis control group completed the Multidimensional Fatigue Inventory-20 questionnaire. Patients with psoriasis also reported joint pain intensity, pruritus, skin pain, and sleep problems using a numerical rating scale. Linear regression models were applied to continuous outcomes, and beta coefficients (ß) for the slopes were estimated with 95% confidence intervals (CIs). RESULTS: Among 2741 adults with psoriasis (of which 593 also had PsA) and 3788 controls, the impact on total fatigue was greatest for PsA (ß = 5.22; 95% CI, 3.55-6.90), followed by psoriasis (ß = 2.10; 95% CI, 0.96-3.25), compared with the general population (Ptrend < .0001). Among patients with psoriasis with or without PsA, increasing joint pain intensity was associated with overall fatigue (ß = 2.23 [95% CI, 2.03-2.44] for each 1-point increase in joint pain numerical rating scale score). LIMITATIONS: We lacked information on the effect of pharmacotherapy. CONCLUSIONS: These findings highlight the importance of a symptom-based approach when treating psoriasis, rather than focusing on objective severity measures alone.

Online Depiction of Urticaria Is Often Flawed and Does Not Reflect the Spectrum of Clinical Manifestation.

INTRODUCTION: The internet is a popular source of health information including images of disease manifestations. Online photographs of skin lesions may aid patients in identifying their disease, if these pictures are of good quality and of the disease they claim to show. If not, patients may be at risk of delayed diagnosis, misdiagnosis, and suboptimal treatment. For urticaria, the mismatch rate and quality of online pictures are unknown. The objective of this study was therefore to evaluate the content and quality of online images of urticaria. METHODS: The search term "urticaria" was applied to Google Images and Shutterstock. The top 100 photographs from each search engine were retrieved on October 9th, 2022. Illustrations, drawings, and heavily edited photographs were excluded. Each image was evaluated for patient characteristics, characteristics of urticarial lesions, and image quality. RESULTS: Across 194 unique images of urticaria (after removing duplicates), 35 (18.0%) did not depict urticarial lesions, and 38 (19.6%) were ambiguous. Less than two-thirds of images 121 (62.4%) showed bona fide urticarial lesions. Pictures of urticarial lesions under-represented children and did not reflect female preponderance of the disease. Images predominantly depicted urticaria lesions on Caucasian skin (59.8%) and were typical of spontaneous rather than inducible urticaria. Only 3 (1.5%) pictures showed angioedema, a common clinical sign in patients with urticaria. The overall quality of online urticaria pictures was mostly good or very good. CONCLUSION: Physicians and patients should be aware that one in five online pictures of urticaria does not show urticarial skin lesions, and children, females, non-Caucasian patients, inducible urticaria, and angioedema are under-represented. These findings should prompt efforts to improve the accuracy and representativeness of online urticaria pictures.

The Agreement between Consumer-Driven Self-Assessment of Psoriasis Severity and Physician-Assessed Severity Based on Patient-Taken Photographs Is Weak: A Cross-Sectional Study.

INTRODUCTION: Digital advancements have given access to huge amounts of real-world data (RWD) widely used for dermatological research. OBJECTIVES: The objective of this study was to investigate the agreement between consumer-driven self-assessed psoriasis severity and physician-assessed severity based on photographs. METHODS: Customer IDs in the NØIE database (Danish skincare company) from 2009 to 2022 with a smartphone photograph of psoriasis vulgaris on the body and a corresponding completed questionnaire were included. Smartphone photographs were evaluated by a physician-assessing erythema, induration, and scaling on a scale from 0 to 4 based on Psoriasis Area Severity Index (PASI). Self-assessment was done on a scale from 0 to 10 and converted to 0-4 scale (0 converted to 0; 1-3 to 1; 4-6 to 2; 7-8 to 3; and 9-10 to 4). Intraclass correlation coefficients with 95% confidence intervals (CIs) were calculated. RESULTS: In total, 187 patients (63% women) with mean age of 38 years were included. Self-assessment scores were higher than physicians' assessment scores for all groups, and scaling was closest to the physicians' assessment, while erythema and induration had a greater distance between the physicians' and patients' assessment. The correlation between self-assessed and physician-assessed psoriasis severity for all patients was 0.23 (95% CI: 0.0-0.92); 0.34 (95% CI: 0.0-0.95) for chronic patients; and 0.09 (-0.01 to 0.82) for non-chronic patients. The agreement was better for men (0.53 [-0.02 to 0.98]) than for women (0.12 [-0.01 to 0.84]). CONCLUSION: There was weak agreement between self-assessed psoriasis severity and photographically assessed severity by the physician. Consumer-driven RWD should be interpreted with caution.

Risk Factors that Impact Treatment with Oral Janus Kinase Inhibitors Among Adult Patients with Atopic Dermatitis: A Nationwide Registry Study.

The European Medicines Agency recently limited the use of oral Janus kinase inhibitors in certain patient populations, including those with atopic dermatitis. This cross-sectional study used the Danish national registers and Danish Skin Cohort to assess the prevalence of risk factors that potentially impact choice of treatment with oral Janus kinase inhibitors in adult patients with atopic dermatitis. From the Danish national registers and Danish Skin Cohort, 18,618 and 3,573 adults with atopic dermatitis, respectively, were identified. Half of the patients (49.5%) had, at some point, been registered to have at least 1 risk factor that could impact treatment with oral Janus kinase inhibitors. Non-modifiable risk factors recorded were cancer (5.6%), major adverse cardiovascular events (2.6%), venous thromboembolism (2.0%), smoking history (15.6%), and age ≥ 65 years (12.4%). Among patients ≥ 65 years of age, the mean (standard deviation) number of risk factors were 3 (1.4), and almost half of these patients had, at some point, been registered to have 1 or more non-modifiable risk factors in addition to their age. In conclusion, risk factors that may impact treatment with oral Janus kinase inhibitors were frequent in Danish adults with atopic dermatitis, especially among older individuals. Dermatologists need support and continuously updated long-term safety data when risk-evaluating patients with atopic dermatitis prior to initiation of advanced.

Impact of the pre-biologic treatment journey on biologic drug survival in psoriasis: A nationwide cohort study.

BACKGROUND: It is unknown whether the pre-biologic treatment journey affects subsequent biologic drug survival. OBJECTIVE: To examine the potential impact of a complex treatment journey on subsequent biologic drug survival in patients with psoriasis. METHODS: The study utilized longitudinal data from Danish national registries and included all patients who, for the first time, initiated a biological treatment for psoriasis. Maximum follow-up was 5 years and patients were included from 1 January 2010 to 30 June 2021. The study used three definitions of exposure to a complex treatment journey and the following conventional systemic treatments: acitretin, cyclosporine, dimethyl fumarate and methotrexate. The first definition was the cumulative number of treatment series. The second definition comprised the number of unique treatments. The third definition was time from the first conventional systemic treatment to biological therapy. Drug survival for the three definitions were illustrated using Kaplan-Meier curves and compared using log-rank test. The sensitivity analysis largely confirmed these findings by grouping patients according to pharmacotherapy. RESULTS: A total of 2496 patients were included in the study, with 1380 (55.3%) receiving adalimumab, 608 (24.4%) receiving ustekinumab, 271 (10.9%) receiving secukinumab, 166 (6.7%) receiving etanercept and 71 (2.8%) receiving infliximab. The mean age at initiation of biologics was 43.6 years (standard deviation (SD) 15.2 years), and most patients were male (62.9%). During the follow-up of 5477 patient years, 1953 patients (78.2%) reached the main endpoint of discontinuation. Using a log-rank test, the probability of remaining on treatment was unaffected by the three definitions of complexity of the treatment journey. CONCLUSION: None of the three exposures used to assess the complexity of the pre-biologic treatment journey appeared to impact drug survival. As long as patients experience adequate disease control, these results suggest that conventional systemic treatment do not negatively impact the drug survival of subsequent biologics.

Psychosocial and mental impact of alopecia areata: Analysis of the Danish Skin Cohort.

IMPORTANCE: Alopecia areata (AA) carries a psychological burden for patients beyond hair loss. However, quality-of-life measurement tools such as EQ-5D used in clinical trials may not adequately capture the burden of AA, the perceived stigmatization or the psychosocial impact of AA. OBJECTIVE: To investigate the potential association between disease severity and the degree of social isolation, perceived stigmatization, anxiety and depression, alcohol consumption and work absenteeism using multiple PRO measures in patients with AA. DESIGN, SETTING AND PARTICIPANTS: Using the Danish Skin Cohort, the study included adult patients diagnosed with AA. The study included multiple PRO measures, including Skindex-16, EQ-5D-5L, Work Productivity and Activity Impairment (WPAI), Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) and the Alopecia Areata Symptom Impact Scale (AASIS). The questionnaires were dispatched to the patients in January 2023. The severity of AA was determined based on scalp involvement using a modified Alopecia Areata Scale. Multiple multivariate linear regressions were conducted using Skindex-16, AASIS and WPAI, while multivariate logistic regressions were applied to HADS, AUDIT-C and EQ-5D-5L. RESULTS: A total of 376 patients were included, of which 177 (47%) had severe disease, 41 (11%) had moderate disease, 94 (25%) had mild disease, and 64 (17%) were in remission. The median age of patients was 55 (IQR, 47-66 years) and most were female (70%). Skindex-16 and AASIS were the only PRO measures able to distinguish between severity. For these scores, moderate and severe diseases, female sex, and involvement of eyebrows increased the score and negatively impacted patient quality of life. CONCLUSION AND RELEVANCE: The results indicate the importance of using the proper tool for the intended measurement of quality of life and that factors such as the severity of AA, as well as female sex and involvement of the eyebrows, may potentially increase the psychosocial burden of AA.

Demographics, characteristics and medical treatment among adults with hand eczema in Denmark. A cross-sectional validation and registry-based study.

BACKGROUND: The international classification of diseases, 10th revision (ICD-10) includes several unvalidated diagnostic codes for hand eczema (HE). Knowledge is sparse on HE patient characteristics. OBJECTIVES: To validate selected HE ICD-10 codes in the Danish National Patient Registry (DNPR) and describe disease characteristics, lifestyle factors and medication use in adult HE patients. METHODS: Nineteen HE ICD-10 codes were selected and validated based on patient charts. Five cohorts were constructed based on the diagnostic code, DL30.8H (HE unspecified), in the DNPR: (i) patients with DL30.8H code (n = 8386), (ii) patients with DL30.8H code, but without atopic dermatitis (AD) (n = 7406), (iii) sex- and age-matched general population (n = 8386) without HE. Two additional cohorts nested in the DNPR included participants from the Danish Skin Cohort, (iv) patients with DL30.8H code but without AD (n = 1340) and (v) general population cohort (n = 9876). RESULTS: ICD-10 codes revealed positive predictive values ≥90% except irritant contact dermatitis (unspecified) (79.7%) and hyperkeratotic hand and foot eczema (84.1%). HE patients were most often women, middle-aged or older, of Danish ethnicity, had an atopic medical history and were smokers. Topical corticosteroid prescriptions were almost doubled in HE cohorts compared to general populations. CONCLUSION: We validated several HE ICD-10 codes and identified important HE patient characteristics.

Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study.

BACKGROUND: Concern about disease exacerbations and fear of reactions after coronavirus disease 2019 (COVID-19) vaccinations are common in chronic urticaria (CU) patients and may lead to vaccine hesitancy. OBJECTIVE: We assessed the frequency and risk factors of CU exacerbation and adverse reactions in CU patients after COVID-19 vaccination. METHODS: COVAC-CU is an international multicenter study of Urticaria Centers of Reference and Excellence (UCAREs) that retrospectively evaluated the effects of COVID-19 vaccination in CU patients aged ≥18 years and vaccinated with ≥1 dose of any COVID-19 vaccine. We evaluated CU exacerbations and severe allergic reactions as well as other adverse events associated with COVID-19 vaccinations and their association with various CU parameters. RESULTS: Across 2769 COVID-19-vaccinated CU patients, most (90%) received at least 2 COVID-19 vaccine doses, and most patients received CU treatment and had well-controlled disease. The rate of COVID-19 vaccination-induced CU exacerbation was 9%. Of 223 patients with CU exacerbation after the first dose, 53.4% experienced recurrence of CU exacerbation after the second dose. CU exacerbation most often started <48 hours after vaccination (59.2%), lasted for a few weeks or less (70%), and was treated mainly with antihistamines (70.3%). Factors that increased the risk for COVID-19 vaccination-induced CU exacerbation included female sex, disease duration shorter than 24 months, having chronic spontaneous versus inducible urticaria, receipt of adenovirus viral vector vaccine, having nonsteroidal anti-inflammatory drug/aspirin intolerance, and having concerns about getting vaccinated; receiving omalizumab treatment and Latino/Hispanic ethnicity lowered the risk. First-dose vaccine-related adverse effects, most commonly local reactions, fever, fatigue, and muscle pain, were reported by 43.5% of CU patients. Seven patients reported severe allergic reactions. CONCLUSIONS: COVID-19 vaccination leads to disease exacerbation in only a small number of CU patients and is generally well tolerated.

Tumor necrosis factor-α inhibitor treatment of acne fulminans - a clinical and literature review.

Acne fulminans (AF) is a rare, serious, sudden-onset and long-lasting skin disease that causes scarring of face and body. Standard treatment with combined long-term isotretinoin and prednisolone is not always sufficient and has a well-known propensity for adverse effects leaving an unmet need for improved therapy. Case reports suggest that tumor necrosis factor (TNF)-α inhibitors may play a role in the management of AF. In a 3-year retrospective data collection from two dermatology centers and literature review of clinical cases of acne fulminans treated with anti-TNF-α therapy, three clinical cases and twelve literature cases were identified. A total of five different TNF-α inhibitors have been tested, with adalimumab being the most commonly used. Clinical response was seen after 1 month in 2/3 (67%) clinical cases and 5/12 (42%) literature cases, respectively, and treatment was successful in 2/3 (67%) and 11/12 (92%) after a median 3-7 months. All reported adverse effects were mild and reversible. Anti-TNF-α treatment may provide rapid improvement in patients with AF when initial treatment with isotretinoin and prednisolone fails. However, randomized controlled trials are lacking, and exact dosage and timing need to be explored before clinical implementation.

Architecture of skin inflammation in psoriasis revealed by spatial transcriptomics.

Psoriasis is a chronic inflammatory skin disease, thought to be predominantly mediated by TH17 cells. Significance of other inflammatory pathways and the innate immune system is not well understood and the spatial heterogeneity of inflammation in the skin has largely been overlooked. Our aim was to create a comprehensive map of skin inflammation in psoriasis, exploring the tissue patterning of inflammation. In situ whole transcriptome sequencing (spatial sequencing) was performed on lesional psoriatic skin in four patients with moderate-to-severe disease to quantify all expressed genes within a tissue section. Transcriptional analysis revealed three major inflammatory niches in psoriasis skin, each with distinct cytokine circuits and chemokines: the hyperplastic epidermis, upper (papillary) dermis, and reticular dermis. Interestingly, key cytokines such as IL-23, IL-17 s, and TNFα were not notably present in the skin's transcriptomic signature. Unexpectedly, IL-32 showed strong expression in the dermis. Our findings underscore the complexity of psoriatic inflammation, highlighting its architectural heterogeneity and the roles of innate cytokines. Both IL-32 and IL-1 family cytokines appear to play critical roles in the dermal and epidermal inflammation, respectively, and may provide pharmacological targets to improve the control of the inflammatory process.

Skin biomarkers predict development of atopic dermatitis in infancy.

BACKGROUND: There is currently no insight into biomarkers that can predict the onset of pediatric atopic dermatitis (AD). METHODS: Nested in a prospective birth cohort study that examined the occurrence of physician-diagnosed AD in 300 children, 44 random children with onset of AD in the first year of life were matched on sex and season of birth with 44 children who did not develop AD. Natural moisturizing factor (NMF), corneocyte surface protrusions, cytokines, free sphingoid bases (SBs) of different chain lengths and their ceramides were analyzed from tape strips collected at 2 months of age before onset of AD using liquid chromatography, atomic force microscopy, multiplex immunoassay, and liquid chromatography mass spectrometry, respectively. RESULTS: Significant alterations were observed for four lipid markers, with phytosphingosine ([P]) levels being significantly lower in children who developed AD compared with children who did not (median 240 pmol/mg vs. 540 pmol/mg, p < 0.001). The two groups of children differed in the relative amounts of SB of different chain lengths (C17, C18 and C20). Thymus- and activation-regulated chemokine (TARC/CCL17) was slightly higher in children who developed AD, whereas NMF and corneocyte surface texture were similar. AD severity assessed by the eczema area and severity index (EASI) at disease onset was 4.2 (2.0;7.2). [P] had the highest prediction accuracy among the biomarkers (75.6%), whereas the combination of 5 lipid ratios gave an accuracy of 89.4%. CONCLUSION: This study showed that levels and SB chain length were altered in infants who later developed AD, and that TARC/CCL17 levels were higher.

The association between Staphylococcus aureus colonization on cheek skin at 2†months and subsequent atopic dermatitis in a prospective birth cohort.

BACKGROUND: Staphylococcus aureus may worsen already established atopic dermatitis (AD), but its primary role in the aetiopathogenesis and severity of AD is unclear. OBJECTIVES: To compare the prevalence of S. aureus colonization in early infancy in children who developed AD during the first 2 years of life with children who did not. METHODS: In this prospective birth cohort study, which included 450 infants, we analysed bacterial swabs collected from cheek skin at 0 and 2 months of age. The development of AD, and its severity, was diagnosed by a physician and monitored prospectively for 2 years. Information on parental atopy, filaggrin gene mutation status and use of antibiotics and emollients was included in the analyses. RESULTS: At birth, the occurrence of S. aureus colonization was similar in infants who developed subsequent AD and those who did not. At 2 months of age, S. aureus colonization was more common in children who later developed AD (adjusted hazard ratio 1.97, 95% confidence interval 1.21-3.19; P = 0.006). No association was found between S. aureus colonization and AD severity or age at onset. CONCLUSIONS: It remains unknown whether colonization with S. aureus may directly increase the risk of AD, or whether it should be considered as secondary to skin barrier impairment or a skewed immune activity, but according to our findings, S. aureus colonization is more commonly increased at 2 months of age in children who later developed AD.

The usefulness of YouTube videos as a source of information in asthma.

BACKGROUND: Patient education is a key element in the management of asthma. AIMS: This study aimed to evaluate the popularity and usefulness of YouTube videos on asthma. METHODS: Two authors screened and evaluated the 200 most popular videos. Data on likes, dislikes, views, comment, source of uploader, days since upload, and usefulness were recorded and included for analyses. The usefulness of the videos was categorized as follows: useful, misleading, or neutral. Misleading videos provided at least one scientifically incorrect detail, whereas useful videos contained scientifically correct information. RESULTS: A total of 130 videos were included, and the total number of views was 100,290,242 with a total duration of 29 h and 8 min. While 26.6% of videos were uploaded by TV shows and YouTube channels, only 7.7% were uploaded by lung specialists. 65.4% of the videos contained scientifically correct information, whereas 18.5% contained misleading information. Although videos from medical professionals had a higher quality than videos from YouTube channels and TV shows, the latter were more popular. Misleading videos had numerically, but not statistically significant higher views compared with useful videos. CONCLUSIONS: YouTube videos on asthma are popular in terms of viewer interaction, and the popularity is not restricted to videos uploaded by professional sources. Although more than half of the videos were found to be useful, a non-negligible proportion of videos were assessed as misleading. The usefulness of YouTube videos on asthma is variable and initiatives should be taken to increase the potential of YouTube as an useful source in patient education.

Risk of Atopic Disorders in Patients with Chronic Urticaria: A Systematic Review and Meta-Analysis.

BACKGROUND: Chronic urticaria (CU) has been associated with several systemic and autoimmune disorders. The association with atopic disorders is however controversial. The objective of this study was to perform a systematic review and meta-analysis to assess the association between CU and the atopic disorders: atopic dermatitis (AD), asthma, and allergic rhinoconjunctivitis (ARC). METHODS: Search hits from PubMed, Embase, Cochrane Library, and Web of Science were systematically reviewed. English papers from 2000 to present, containing original data of the association (prevalence, incidence, or risk) between CU and any atopic disorder(s), were included. Pooled point prevalence and OR with 95% confidence intervals were calculated with a random effects model. RESULTS: A total of 8,108 search hits were screened and reviewed. Thirty-eight studies met all inclusion criteria. The estimated pooled point prevalence of AD, asthma, and ARC in CU was 7% (5-11%, I2 = 99%), 12% (9-15%, I2 = 100%), and 22% (16-29%, I2 = 100%), respectively. Pooled ORs were estimated to 2.75 (2.05-3.68, I2 = 94%) for AD, 1.87 (1.01-3.45, I2 = 100%) for asthma, and 2.94 (1.84-4.68, I2 = 100%) for ARC. CONCLUSION: Pooled point prevalences of atopic disorders in CU were comparable to the general population. However, studies that compared prevalences with controls from the same population all found a significantly increased risk of atopic disorders in CU. Results should however be interpreted with caution as high heterogeneity was found in all analyses.