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Background: Oral Janus kinase inhibitors (JAKi) have been approved for the treatment of several chronic inflammatory conditions, including rheumatoid arthritis (RA) and atopic dermatitis (AD). Prompted by new evidence, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) recently reassessed the benefit–risk balance of oral JAKi. The PRAC recommended that oral JAKi should be used only if no suitable alternatives are available in patients ≥65 years of age, or who have a history of atherosclerotic cardiovascular (CV) disease, other CV risk factors (e.g. history of long‐term smoking) or have malignancy risk factors, and used with caution in patients at risk of pulmonary embolism or deep vein thrombosis. The European Commission's final decision was issued in March 2023. Objectives: Our goal was to highlight the PRAC recommendations, especially in the context of oral JAKi use in AD. Methods: Authors summarized the PRAC recommendations, the new clinical evidence on oral JAKi safety and key differences between patients with RA and AD. Results: Risk of developing adverse events of special interest (e.g. cardiovascular events, malignancy) is higher in patients with RA than in patients with AD, because of the higher prevalence of the underlying risk factors. Conclusions: The benefit–risk profile of JAKi approved for AD remains favourable, including use as first‐line systemic therapy for patients with AD <65 years of age and without CV or malignancy risk factors. [ABSTRACT FROM AUTHOR]

Background Early prediction of therapeutic response can optimize treatment strategies in atopic dermatitis (AD). Baricitinib is approved for moderate-to-severe AD in Europe, Japan and other countries. Objectives To identify early clinical improvements that can reliably predict a later clinical response to baricitinib in adults with moderate-to-severe AD. Methods Using data from one topical corticosteroid combination study [BREEZE-AD7 (NCT03733301)] and data pooled from two monotherapy studies [(BREEZE-AD1 (NCT03334396) and BREEZE-AD2 (NCT03334422)], we calculated the sensitivity and specificity, along with the positive predictive value (PPV) and negative predictive value (NPV), of predefined changes in single and combined clinical scores at weeks 2, 4 and 8, to predict clinical response at week 16. Clinical response was defined as ≥ 75% improvement in Eczema Area and Severity Index (EASI 75), ≥ 4-point improvement in Itch Numeric Rating Scale (Itch NRS ≥ 4), or a combination of both. Results Composite predictors had higher predictive accuracy for week 16 response outcomes than did single parameters. This was evident as early as week 4 for the combination of EASI 50 or Itch NRS ≥ 3 and of validated Investigator Global Assessment for AD (vIGA-AD) score ≤ 2 or Itch NRS ≥ 3 (sensitivity 87–100%; NPV 68–100%). The predictive accuracy of these composite clinical predictors for week 16 response outcomes was highest at week 8 (sensitivity 92–100%; NPV 80–100%). At both weeks 4 and 8, EASI 50 or Itch NRS ≥ 3 had higher sensitivity and NPV than did vIGA-AD score ≤ 2 or Itch NRS ≥ 3. Conclusions Improvement in signs and symptoms early during treatment with baricitinib 4 mg once daily predicts clinical response at week 16, providing a tool for dermatologists when choosing treatment strategies for patients with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Background: Measuring patient‐reported outcomes is crucial to fully capture the burden of chronic hand eczema (CHE). Objectives: To assess the effect of delgocitinib cream on itch, pain and nine additional key signs and symptoms reported by patients with CHE using the Hand Eczema Symptom Diary (HESD). Methods: In a double‐blind, phase IIb dose‐ranging trial (NCT03683719), 258 adults with mild to severe CHE were randomized to delgocitinib cream 1, 3, 8 or 20 mg/g or cream vehicle twice daily for 16 weeks. Patients assessed 11 signs and symptoms of CHE daily through the HESD using an 11‐point numeric rating scale; this was an exploratory endpoint. Results: Delgocitinib cream 20 mg/g was associated with an early and sustained reduction in itch and pain, along with clinically relevant reductions of ≥4 points from baseline to Week 16 in 48.4% and 63.6% of patients, respectively (17.9% and 5.9% with cream vehicle). There were improvements versus cream vehicle in all assessed CHE signs and symptoms (20 mg/g, p < 0.05). Conclusions: Delgocitinib cream reduced itch, pain and other signs and symptoms in patients with CHE. This data correlated with clinician‐reported outcomes, indicating that the HESD may be a useful assessment tool for CHE management. [ABSTRACT FROM AUTHOR]

Background Lebrikizumab is a novel, high-affinity monoclonal antibody that selectively binds to interleukin (IL)-13. Objectives To evaluate the efficacy and safety of lebrikizumab monotherapy in adolescent and adult patients with moderate-to-severe atopic dermatitis (AD) over 52 weeks of treatment in ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967). Methods Patients who responded to lebrikizumab 250 mg every 2 weeks (Q2W) at the end of the 16-week induction period were re-randomized 2 : 2 : 1 to receive lebrikizumab Q2W, lebrikizumab 250 mg every 4 weeks (Q4W) or placebo Q2W (lebrikizumab withdrawal) for 36 additional weeks. Response at week 16 was defined as achieving a 75% reduction in Eczema Area Severity Index (EASI 75) or an Investigator's Global Assessment (IGA) of 0 or 1, with a ≥ 2-point improvement and no rescue medication use. Multiple imputation was used to handle missing data. Intermittent use of topical therapy was permitted during the maintenance period. Results After 52 weeks, an IGA of 0 or 1 with a ≥ 2 point improvement was maintained by 71.2% of patients treated with lebrikizumab Q2W, 76.9% of patients treated with lebrikizumab Q4W and 47.9% of patients in the lebrikizumab withdrawal arm. EASI 75 was maintained by 78.4% of patients treated with lebrikizumab Q2W, 81.7% of patients treated with lebrikizumab Q4W and 66.4% of patients in the lebrikizumab withdrawal arm at week 52. Across treatment arms, proportions of patients using any rescue therapy were 14.0% (ADvocate1) and 16.4% (ADvocate2). During the combined induction and maintenance periods of ADvocate1 and ADvocate2, 63.0% of lebrikizumab-treated patients reported any treatment emergent adverse event, with most events (93.1%) being mild or moderate in severity. Conclusions After a 16-week induction period with lebrikizumab Q2W, lebrikizumab Q2W and Q4W maintained similar improvement of the signs and symptoms of moderate-to-severe AD, with a safety profile consistent with previously published data. [ABSTRACT FROM AUTHOR]

Purpose: Topical treatments for mild-to-moderate (MM) atopic dermatitis (AD) include emollients, corticosteroids, calcineurin inhibitors, a Janus kinase inhibitor, and a phosphodiesterase 4 inhibitor, which differ in multiple ways. This study aimed to quantify the conditional relative importance (CRI) of attributes of topical treatments for MM AD among adult and adolescent patients and caregivers of children with MM AD. Materials and methods: A discrete-choice experiment (DCE) survey was administered to US adults and adolescents with MM AD and caregivers of children with MM AD. Each choice task comprised 2 hypothetical topical treatments characterized by efficacy, adverse events, vehicle, and application frequency. Data were analyzed using a random-parameters logit model to calculate the CRI of each attribute. Results and conclusions: 300 adults, 331 adolescents, and 330 caregivers completed the DCE. Avoiding changes in skin color (CRI 29.0) and time until itch improves (26.6) were most important to adults, followed by time until clear/almost clear skin (17.8). Application frequency (3.0) did not have a statistically significant impact on adults’ choices. Adolescents were less concerned about changes in skin color than adults or caregivers; caregivers were less concerned about time until clear/almost clear skin than patients. Physicians should consider age-relevant aspects of preferences in treatment discussions with patients and caregivers. [ABSTRACT FROM AUTHOR]

The article discusses the use of topical corticosteroids (TCS) in the treatment of inflammatory skin diseases. While TCS have been widely used and proven effective, prolonged use or application in areas with high absorption rates can lead to adverse effects such as striae formation, adrenal suppression, and Cushing syndrome. Recent studies have also associated TCS use with an increased risk of osteoporosis and fractures, particularly in women and younger individuals. The article emphasizes the need to reassess the position of TCS in treatment guidelines and consider alternative non-steroidal therapies with minimal systemic absorption. [Extracted from the article]

Background: Rosacea is a common chronic inflammatory facial skin disorder. Standardized evaluation of the severity and extent of rosacea is important for baseline assessment and treatment effect. The currently used Investigator's Global Assessment (IGA) is unspecific and fails to consider subtypes/phenotypes of rosacea and area involvement. The Rosacea Area and Severity Index (RASI) was developed to give a more nuanced evaluation of rosacea features in four facial skin areas adjusted to the relative importance of each area of the face to obtain an overall severity score. Objectives: To validate RASI against the IGA and to assess the inter‐ and intraobserver reliability for RASI. Methods: Sixteen dermatologists evaluated photographs of 60 adult patients with rosacea (3 photographs per patient, one from the front and one from each side). IGA and RASI scores were performed for interobserver reliability assessment. To determine intraobserver reliability, 14 dermatologists evaluated 10 other patients twice with at least 1 week interval. Results: The IGA and RASI correlated well (Spearman correlation coefficient (SCC) = 0.75, 95% confidence interval (CI) = 0.72–0.78). Interobserver reliability was moderate for RASI and poor to moderate for IGA. Reliability was strongest for rhinophyma, followed by papules/pustules and erythema, and rather weak for telangiectasia. For area scores, interobserver reliability was strongest for cheeks, followed by nose, chin and forehead. We found a moderate‐to‐strong intraobserver agreement both for IGA and RASI. Conclusions: We have designed a new practical tool to examine clinical severity of rosacea. RASI proved simple and reliable in scoring clinical severity of rosacea with an agreement comparable to the currently used IGA although RASI will provide a more nuanced view of the current rosacea extent and severity. We suggest that RASI is used in the daily clinical setting as well as in clinical studies assessing the efficacy of rosacea therapies. [ABSTRACT FROM AUTHOR]

Baricitinib is an oral selective Janus kinase 1/2 inhibitor approved for moderate-to-severe atopic dermatitis (AD) in adults. To evaluate absolute Eczema Area and Severity Index (EASI) and SCORing of Atopic Dermatitis (SCORAD) outcomes over 16 weeks and to link disease severity categories to quality of life (QoL) improvements. This post-hoc analysis included patients enrolled in Phase3 monotherapy (BREEZE-AD1/AD2) and topical corticosteroid (TCS) combination therapy (BREEZE-AD7) trials and analyzed baricitinib 2 and 4 mg vs. placebo. Categorical outcomes were analyzed using Fisher's exact test. Significantly more baricitinib-treated patients reached EASI ≤ 7 and SCORAD < 25 as early as week 1 in monotherapy and week 2 in TCS combination therapy, compared to placebo. Significant response vs. placebo was sustained until week 16 for EASI ≤ 7 (AD1/2 [p-value vs. placebo]: 2 mg = 19.9%, 4 mg = 25.4% [p = 0.001] and AD7: 2 mg = 40.4% [p = 0.087], 4 mg = 48.6% [p = 0.003]) and SCORAD < 25 (AD1/2: 2 mg = 12.2%, 4 mg = 19.4% [p = 0.001] and AD7: 2 mg = 30.3% [p = 0.025], 4 mg = 34.2% [p = 0.004]) severity categories. These effects were accompanied by rapid improvements in QoL. Baricitinib-treated patients rapidly achieved recommended absolute EASI and SCORAD treatment outcomes which were sustained until week 16. Improvements in QoL were greater than EASI severity categories reflected, indicating that physician-assessed scores do not necessarily correlate with patients' impression of AD severity. [ABSTRACT FROM AUTHOR]

Patients who completed the originating studies, BREEZE-AD1 (NCT03334396), BREEZE-AD2(NCT03334422), and BREEZE-AD7 (NCT03733301), were eligible for enrollment in the multicenter,phase-3, long-term extension study BREEZE-AD3 (NCT03334435). At week 52, responders and partial responders to baricitinib 4 mg were re-randomized (1:1) into the sub-study to dose continuation (4 mg, N = 84), or dose down-titration (2 mg, N = 84). Maintenance of response was assessed from week 52 to 104 of BREEZE-AD3. Physician-rated outcomes included vIGA-AD (0,1), EASI75, and mean change from baseline in EASI. Patient-reported outcomes included DLQI, P OEM total score, HADS, and from baseline: WPAI (presenteeism, absenteeism, overall work impairment, daily activity impairment) and change from baseline in SCORAD itch and sleep loss. With continuous treatment with baricitinib 4 mg, efficacy was maintained up to week 104 in vIGA-AD (0,1), EASI75, EASI mean change from baseline, SCORAD itch, SCORAD sleep loss, DLQI, P OEM, HADS, and WPAI (all scores). Patients down-titrated to 2 mg maintained most of their improvements in each of these measures. The sub-study of BREEZE AD3 supports flexibility in baricitinib dosing regimens. Patients who continued treatment with baricitinib 4 mg and down-titrated to 2 mg maintained improvements in skin, itch, sleep, and quality of life for up to 104 weeks. [ABSTRACT FROM AUTHOR]

Background: The accuracy of self‐reported hand eczema (HE) is currently unclear, and it is unknown how well self‐reported signs and symptoms of skin lesions that indicate HE correlate with self‐reported HE. Objectives: To correlate self‐reported signs and symptoms of skin lesions on the hands with self‐reported HE, to assess the sensitivity and specificity, and to suggest a definition for HE. Method: Seven hundred ninety‐five (47.8%) of 1663 invited healthcare workers completed a digital questionnaire, and were asked to report if they experienced HE or any of the following skin signs/symptoms in past 11 months: scaling, erythema, fissures, vesicles, dryness, itch, stinging. Results: HE during the past 11 months was reported by 11.9%. Of these, 91.4% reported at least one skin sign versus 32.3% of those without self‐reported HE. The highest sensitivity and specificity were found for erythema (77.4% and 78.2%, respectively) and itch (78.5% and 78.6%, respectively), both separately and combined. The combination of ≥2 signs (erythema, scaling, fissures and vesicles) and itch, reached a sensitivity of 52.7% and specificity of 93.9%. Conclusion: The marked difference between self‐reported HE and signs/symptoms highlights the importance of differentiating between data based on self‐reported HE and signs/symptoms. As a first step towards diagnostic HE criteria, ≥2 signs combined with itch could be considered, but clinical studies are needed to verify the precision. [ABSTRACT FROM AUTHOR]

Background: Phase 3 trials have assessed efficacy of abrocitinib versus placebo in moderate-to-severe atopic dermatitis, a common immunoinflammatory skin disease. This study assessed the efficacy and safety of abrocitinib versus dupilumab.Methods: This randomised, double-blind, double-dummy, active-controlled, parallel-treatment, phase 3 trial enrolled adults with moderate-to-severe atopic dermatitis who requir=ed systemic therapy or had inadequate response to topical medications. Participants were enrolled from 151 sites, located in Australia, Bulgaria, Canada, Chile, Finland, Germany, Hungary, Italy, Latvia, Poland, Slovakia, South Korea, Spain, Taiwan, and the USA. These participants were then randomly assigned (1:1) with block randomisation to receive oral abrocitinib (200 mg per day) or subcutaneous dupilumab (300 mg every 2 weeks) for 26 weeks. Participants were required to apply topical corticosteroids (medium or low potency), topical calcineurin inhibitors, or a topical phosphodiesterase 4 inhibitor to active lesion areas. Primary endpoints were response based on achieving a 4 point or higher improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) at week 2 and a 90% or better improvement in Eczema Area and Severity Index (EASI-90) at week 4. Family-wise type 1 error was controlled via a sequential multiple-testing procedure (two sided, α=0·05). Randomly assigned participants who received at least one dose of study intervention were included in the efficacy and safety analysis sets. This trial was completed on July 13, 2021 (NCT04345367).Findings: Between June 11, 2020, and Dec 16, 2020, 940 patients were screened and 727 were enrolled (362 in the abrocitinib group and 365 in the dupilumab group). Compared with dupilumab, a larger proportion of patients treated with abrocitinib reached the primary outcomes, PP-NRS4 at week 2 (172 [48%] of 357, 95% CI 43·0-53·4 vs 93 [26%] of 364, 21·1-30·0; difference 22·6%, 15·8-29·5; p<0·0001), and EASI-90 at week 4 (101 [29%] of 354, 23·8-33·2 vs 53 [15%] of 364, 10·9-18·2; difference 14·1%, 8·2-20·0; p<0·0001). Treatment-emergent adverse events were reported by 268 (74%) of 362 patients treated with abrocitinib and by 239 (65%) of 365 patients treated with dupilumab. Two non-treatment-related deaths occurred in the abrocitinib group.Interpretation: Abrocitinib 200 mg per day was more efficacious than dupilumab in adults with moderate-to-severe atopic dermatitis on background topical therapy in inducing early reductions of itch and atopic dermatitis disease signs. Both treatments were well tolerated over 26 weeks.Funding: Pfizer. [ABSTRACT FROM AUTHOR]

Summary: Background: Chronic hand eczema (CHE) is a burdensome disease, and new well‐documented, safe and efficacious treatments are warranted. In a recent CHE phase IIa trial, the pan‐Janus kinase (JAK) inhibitor delgocitinib in an ointment formulation was found to be efficacious and well tolerated. Objectives: This trial assessed the dose response, efficacy and safety of delgocitinib cream in CHE. Methods: In this double‐blind, phase IIb dose‐ranging trial, adults with CHE and a recent history of inadequate response or contraindication to topical corticosteroids were randomized to delgocitinib cream 1, 3, 8, 20 mg g–1 or vehicle treatment twice daily for 16 weeks. The primary endpoint was the Investigator's Global Assessment for CHE (IGA‐CHE) treatment success [0 (clear) or 1 (almost clear) with a ≥ two‐point improvement from baseline to week 16]. Secondary endpoints were the time to IGA‐CHE treatment success and changes in Hand Eczema Severity Index (HECSI); other endpoints were itch and pain numerical rating scale (NRS) scores, and Patient's Global Assessment (PaGA) at week 16. Results: Patients (n = 258) were randomized 1 : 1 : 1 : 1 : 1 to delgocitinib cream 1, 3, 8, 20 mg g–1 or vehicle. A significant dose–response relationship was established for IGA‐CHE (P < 0.025). IGA‐CHE treatment success at week 16 was achieved in 21.2% (1 mg g–1), 7.8% (3 mg g–1), 36.5% (8 mg g–1), 37.7% (20 mg g–1) and 8.0% (vehicle) of patients. Delgocitinib 8 and 20 mg g–1 showed a treatment effect against vehicle (P < 0.001). Similarly, there were improvements in HECSI, itch and pain NRS scores, and PaGA. Delgocitinib cream was well tolerated with the majority of adverse events being mild or moderate and considered unrelated to treatment. The most frequently reported adverse events were nasopharyngitis (17.3–29.4% in delgocitinib groups vs. 40% in vehicle group), eczema (5.8–11.3% in delgocitinib groups vs. 16.0% in vehicle group) and headache (3.8–11.5% in delgocitinib groups vs. 4.0% in vehicle group). Conclusions: In this trial, delgocitinib cream showed a dose–response relationship in terms of efficacy and was well tolerated. [ABSTRACT FROM AUTHOR]

Background: Use of Janus kinase 1 inhibitors in moderate‐to‐severe atopic dermatitis (AD) is associated with incident acne in adolescent and adults that is mostly mild, transient and treatable. There is a need for more knowledge about the risk and severity of acne in patients with AD. Objectives: To examine the prevalence, incidence and risk of acne in adolescents and adults with AD using nationwide prescription data. Methods: A matched cohort study of 6600 adults with AD and 66 000 controls was conducted using routinely and prospectively collected nationwide administrative data. Adjusted hazard ratios (HR) are reported with 95% confidence intervals (CIs). Results: The 12‐month prevalence of acne was 3.7% in the general population and 3.9% among AD patients. The incidence rate of acne was highest among 12‐ to 18‐year‐old AD patients, and overall slightly higher in women with AD compared with males. The overall risk in patients with AD was similar with that of the general population (HR 0.96; 95% CI 0.88–1.06), whereas the risk of being treated for severe acne was reduced in AD patients (HR 0.59; 95% CI 0.47–0.73) and mainly among adolescents and young adults. The HR of acne increased with age reaching 1.41 (95% CI 1.07–1.87) for ages 30–39 years, and 2.07 (95% CI 1.42–3.03) for patients ≥40 years compared with controls. Conclusions: The risk and severity of acne in AD patients change with age and sex, which may be used for the risk assessment of acne following treatment with Janus kinase 1 inhibitors. [ABSTRACT FROM AUTHOR]

Background: Hand eczema is a common inflammatory skin disorder. Health care providers need continuously updated information about the management of hand eczema to ensure best treatment for their patients. Objectives: To update the European Society of Contact Dermatitis guideline on the diagnosis, prevention, and treatment on of hand eczema. Method: The Guideline Development Group (GDG) was established on behalf of the ESCD. A call for interest was launched via the ESCD website and via the ESCD members' mailing list. Appraisal of the evidence for therapeutic and preventive interventions was applied and a structured method of developing consensus was used and moderated by an external methodologist. The final guideline was approved by the ESCD executive committee and was in external review on the ESCD webpage for 1 month. Results: Consensus was achieved for several statements and management strategies. Conclusion: The updated guideline should improve management of hand eczema. [ABSTRACT FROM AUTHOR]

Artificial nail modelling systems (ANMS), encompassing artificial nails and long-lasting nail polish, are sources of acrylate exposure in beauticians and users of ANMS. Hairdressers' exposure to ANMS from self-use and occupational exposure is currently unknown. In 2020 a questionnaire was sent to all hairdressers graduating during 2008 to 2018 in Denmark (n = 4,830). Selfuse of ANMS was reported by 87.6% of respondents (1,251/1,428), and application of ANMS to others was reported by 22.1% (316/1,428). Of these, application to others was performed in a salon by 37.1% (109/294), privately by 51.0% (150/294) and in both settings by 11.9% (35/294). Compliance with glove use was seen in 23.0% (67/291) among those applying ANMS to others. Among hairdressers exposed to ANMS, 4.3% (52/1,218) reported ANMS-related hand eczema. Being a trained beautician (adjusted odds ratio 3.26, 95% confidence interval 1.06-9.99) and having had a positive patch-test to acrylates (adjusted odds ratio 7.70, 95% confidence interval 1.44-41.13) were associated with ANMS-related hand dermatitis. In conclusion, hairdressers have a high prevalence of exposure to ANMS and ANMS-related hand dermatitis. Compliance with glove use when applying ANMS to others is poor. Patch-testing with acrylates is valuable in the diagnostic work-up of hand eczema in hairdressers. [ABSTRACT FROM AUTHOR]

Background: In March 2014, the European Commission issued a new regulation restricting the content of hexavalent chromium (Cr) in leather to no more than 3 mg/kg. We previously performed a questionnaire study in January 2014 to characterize our patients with Cr contact allergy prior to regulatory intervention. Objectives: To assess whether clinical characteristics, self‐reported sources of Cr exposure, and burden of disease changed in patients with Cr allergy over time. Methods: A questionnaire study was performed among 172 adult dermatitis patients with Cr allergy and 587 age‐ and sex‐matched dermatitis patients without Cr allergy. A questionnaire was sent to all dermatitis patients patch tested from 2003 to 2018 in August 2019. Results: The overall response rate was 61.2% (759/1241). Patients with Cr allergy were still more commonly affected by current foot dermatitis (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.07‐7.08) and hand dermatitis (OR 1.98, 95% CI 1.13‐3.49) compared with controls diagnosed during 2013 to 2018. The proportion of patients with Cr allergy reporting dermatitis caused by leather exposure did not change during 2003 to 2012 vs 2013 to 2018 (71.0% vs 66.2%, P =.5). Furthermore, estimates on occupational performance and disease severity (eg, current dermatitis), number of anatomical locations with dermatitis, worst‐case dermatitis, and effect on work were similar in patients with Cr allergy for 2003 to 2012 vs 2013 to 2018. Conclusion: No immediate sign of improvement was found in patients with Cr allergy concerning severity of disease and dermatitis from leather exposures 5 years after adoption of the regulation against hexavalent Cr in leather. The regulation may have to be revised for better protection of those already sensitized. [ABSTRACT FROM AUTHOR]

Introduction: Skin pain (described as discomfort or soreness) is increasingly recognized as a symptom of atopic dermatitis which impacts patient quality of life. This analysis examined the effect of baricitinib on skin pain in atopic dermatitis in three phase 3 studies (BREEZE-AD1, -AD2, and -AD7). Methods: Patients were randomly assigned 2:1:1:1 to receive once-daily placebo, baricitinib 1 mg, 2 mg, or 4 mg in BREEZE-AD1 (N = 624) and -AD2 (N = 615) and 1:1:1 to receive once-daily placebo, baricitinib 2 mg, or 4 mg, with topical corticosteroids, in BREEZE-AD7 (N = 329) for 16 weeks. Patients recorded their skin pain severity using the Skin Pain Numerical Rating Scale (NRS) via an electronic daily diary. Data were analyzed by study as least squares mean change from baseline in daily scores for the randomly assigned patients using mixed model repeated measures analysis. Analysis of Skin Pain NRS response was done using logistic regression using non-responder imputation. Results: Baricitinib produced significant percentage change from baseline compared with placebo in patient-reported skin pain severity by day 2 in BREEZE-AD1 (baricitinib 4 mg − 11.9%, p < 0.001; baricitinib 2 mg − 6.4%, p = 0.016; baricitinib 1 mg − 6.2%, p = 0.016), -AD2 (baricitinib 4 mg − 12.6%, p < 0.001; baricitinib 2 mg − 5.6%, p = 0.036; baricitinib 1 mg − 6.9%, p = 0.011), and -AD7 (baricitinib 4 mg − 6.9%, p = 0.04; baricitinib 2 mg − 7.9%, p = 0.018). A greater proportion of patients treated with baricitinib reported at least a 4-point reduction in Skin Pain NRS score at week 16 (Skin Pain NRS responders) in BREEZE-AD1 (baricitinib 4 mg 25.3%, p < 0.001), -AD2 (baricitinib 4 mg 20.0%, p < 0.001; baricitinib 2 mg 19.0%, p < 0.001), and -AD7 (baricitinib 4 mg 48.8%, p < 0.001; baricitinib 2 mg 45.2%, p = 0.004) compared to placebo. A significantly higher proportion of Skin Pain NRS responders also achieved at least a 4-point improvement in Dermatology Life Quality Index at week 16 when compared with Skin Pain NRS non-responders in BREEZE-AD1 (89.2%, p < 0.0001), -AD2 (92.5%, p < 0.0001), and -AD7 (88.3%, p < 0.0001). Conclusion: Baricitinib improved patient-reported skin pain severity as early as day 2. ClinicalTrials.gov identifiers: BREEZE-AD1, NCT03334396; BREEZE-AD2, NCT03334422; BREEZE-AD7, NCT03733301. [ABSTRACT FROM AUTHOR]

To estimate the cost of illness in adult patients with moderate-to-severe atopic dermatitis (AD) a cohort study was conducted identifying Danish citizens (= 18 years) diagnosed with AD between 1997 and 2018 in the Danish National Patient Register. Moderate-tosevere AD was defined as = 3 hospital contacts regarding AD the first year after diagnosis. Each patient with AD was matched to 3 reference individuals through the Central Person Registry. Societal costs included the direct costs for primary-sector visits, inpatient hospitalizations, outpatient contacts, prescription medicine and indirect costs of lost productivity 3 years before and 5 years after the index date (the study period). A total of 5,245 patients with moderate-to-severe AD were identified. The mean attributable healthcare costs for patients with moderate-to-severe AD were EUR 10,835 (p < 0.0001) during the study period. Moderate-to-severe AD among adults inferred substantial economic burden compared with a group of matched reference individuals. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis imparts a substantial patient burden, including itch, sleep disturbance, and decreased health-related quality of life. Objective: This analysis evaluated changes in patient-reported outcomes of disease-specific signs/symptoms and health-related quality of life in adult and adolescent patients with moderate-to-severe atopic dermatitis treated with once-daily oral abrocitinib 200-mg or 100-mg monotherapy. Methods: Pooled data from one phase IIb (NCT02780167) and two phase III (NCT03349060, JADE MONO-1; NCT03575871, JADE MONO-2) monotherapy trials in adult and adolescent patients with moderate-to-severe atopic dermatitis were analyzed. Patient-reported outcome assessments included: global severity, itch, and multi-item measures that assess other signs and symptoms of atopic dermatitis. Additional patient-reported outcome assessments measured depression, anxiety, fatigue, disease-specific and general health-related quality of life, and work and general productivity among employed patients. Results: Overall, 942 patients were included in this analysis. Improvements were observed from the first post-baseline assessment to week 12 across all patient-reported outcomes, including Patient Global Assessment (PtGA) score of 0/1 (35.5%, 19.8%, and 5.9% for 200 mg, 100 mg, and placebo, respectively), ≥ 4-point improvement in Night Time Itch Scale (NTIS; 57.0%, 42.7%, and 12.7%), change from baseline in Patient-Oriented Eczema Measure (POEM) score (− 11.4, − 8.2, and − 3.4), 1-point improvement in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD; 75.2%, 65.1%, and 33.5%), Hospital Anxiety and Depression Scales (HADS) anxiety (− 2.0, − 1.7, and − 1.0) and depression (− 1.7, − 1.3, and − 0.1). Conclusions: Abrocitinib monotherapy improved disease-specific signs/symptoms and health-related quality of life across multiple domains as reported by adult and adolescent patients with moderate-to-severe atopic dermatitis, complementing clinician-reported efficacy and safety outcomes. Clinical Trial Registration: NCT02780167 (registered 23 May, 2016), NCT03349060 (registered 21 November, 2017), NCT03575871 (registered 3 July, 2018). [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) severity was measured in two phase 3 US studies of crisaborole ointment, 2%, in patients aged ≥ 2 years using the Investigator's Static Global Assessment (ISGA), an FDA-recommended scale. Eczema Area and Severity Index (EASI) is a validated scale used globally to assess AD severity in clinical trials. The objective of this study is to aid interpretability of ISGA by translating ISGA scores to EASI scores. Methods: ISGA was mapped to EASI using published EASI severity strata by Chopra et al. and Leshem et al. and pooled data from phase 3 trials CrisADe CORE 1 and CORE 2, which evaluated crisaborole in patients aged ≥ 2 years with mild-to-moderate AD (crisaborole, n = 1016; vehicle, n = 506). Least squares mean (LSM) percentage change from baseline (%CFB) in EASI and proportion of patients with 50%, 75%, and 90% improvement (EASI-50, EASI-75, and EASI-90, respectively) on day 29 were computed for mapped EASI. The relationship between changes in ISGA and changes in EASI was assessed using data from three abrocitinib trials. Results: ISGA was mapped to EASI using 70,000 random simulations. LSM (standard error) for %CFB in mapped EASI at day 29 (crisaborole versus vehicle) was −26.3% (17) versus 45.2% (35) (P = 0.0671) using Chopra strata and −43.1% (4.6) versus −5.2% (8.4) (P < 0.0001) using Leshem strata. EASI-50, EASI-75, and EASI-90 rates were 72.1% versus 57.6%, 63.0% versus 47.8%, and 55.0% versus 40.1%, respectively, using Chopra strata (P < 0.0001 for each difference). These rates were 68.8% versus 54.0%, 54.8% versus 40.5%, and 38.9% versus 27.2%, respectively (P < 0.0001 for each difference) using Leshem strata. Mean two-point improvement in ISGA was comparable to EASI-90. Conclusion: Mapped EASI results were consistent with ISGA results in crisaborole phase 3 trials. Simulation methodologies yielded consistent results and may aid in interpretability of ISGA across clinical studies. Trial Registration: ClinicalTrials.gov identifier: NCT02118766, NCT02118792. [ABSTRACT FROM AUTHOR]

Introduction: A number of treatments for atopic dermatitis (AD) are available; however, long-term treatment patterns and healthcare consumption in patients with AD are poorly described. Methods: We conducted a registry-based longitudinal drug utilization study among Danish patients with AD that were referred to their first-ever visit at hospital-based dermatology clinics. Their first visit was in the period between 1 January 2005 and 31 December 2012, and patients were followed up to 5 years after their first visit. Results: In total, 8213 people with a first-time hospital dermatologist contact for AD were included in the study (3514 aged 0–9 years, 1501 aged 10–19 years, 3198 aged 20 years or older). At first visit, a baseline history of moderately potent topical corticosteroid (TCS) use was seen among 46.6% of children (0–9 years), whereas potent or very potent TCS use was more frequently among older individuals (e.g., 51.1% and 25.6% of people aged 50 years or older had used potent and very potent TCS, respectively). The median (interquartile range) annual number of visits to general practitioners was 4 (2–7) for children and 5 (2–8) for adults, in the 12 months prior to referral. Three years after referral, these numbers had decreased to 2 (1–4) and 3 (1–6), respectively. In the first year after referral, 6% of patients were prescribed systemic corticosteroids, whereas other systemic therapies were used in 5% or less. Conclusions: After referral, low proportions of patients received systemic treatment, or potent TCS. These findings highlight considerable differences in treatment patterns between general practitioners and private practice dermatologists, compared with hospital-based dermatologists, and emphasize the need for better adherence to evidence-based treatment guidelines. [ABSTRACT FROM AUTHOR]

Background: In 2005, methylisothiazolinone (MI) was allowed as a stand‐alone preservative in cosmetics. This resulted in an epidemic of allergic contact dermatitis to MI, mainly affecting women exposed to leave‐on cosmetics. Consequently, a regulation of Annex V in the European Union in 2017 banned the use of MI in leave‐on cosmetics and reduced the allowed concentration in rinse‐off products. Objective: To analyze the temporal trends in contact allergy to MI in Danish patients in relation to key events including European regulations over time. Methods: A retrospective study of consecutive patients patch tested with methylisothiazolinone from 2005 to 2019. Demographics and clinical characteristics in terms of MOAHLFA (male, occupational, atopic dermatitis, hand dermatitis, leg dermatitis, facial dermatitis and age >40 years), sources of exposure, and clinical relevance were analyzed in relation to key historical events. Results: Three hundred eighty of 12 494 patients (3.0%, 95CI: 2.7–3.4%) tested from 2005 to 2019 were sensitized to MI. An increasing trend in the prevalence of MI contact allergy from 2005 to 2019 (P <.01) was observed, although a decline in the absolute number of patch‐test positive patients was seen from 2013 and onward. A reduction in leave‐on cosmetics as a source of exposure was observed following the legislative ban in 2017, from 24.8% from in 2010 to 2013 to 6.2% in 2017 to 2019 (P <.01). Conclusion: The epidemic of MI contact allergy is declining in absolute terms, although the prevalence in the patch‐tested population has not returned to its pre‐epidemic levels. The legislative regulation of MI in 2017 has been effective in terms of leave‐on cosmetics as a source of exposure in MI allergic patients. The process of post‐marketing risk assessment of contact allergens in the European Union needs improvement. [ABSTRACT FROM AUTHOR]

Little is currently known about possible associations between disease specific characteristics of atopic dermatitis (AD) and use of medical treatments. We explored the use of AD treatments within the past 12 months in Danish adults according to distinct patient characteristics. Patients who had received a diagnosis of AD in a hospital in‐ or outpatient setting as adults were surveyed and data cross‐linked to a national prescription registry. AD severity was measured by the Patient‐Oriented SCORing Atopic Dermatitis (PO‐SCORAD). A total of 3834 patients participated. Use of topical medication in the past 12 months increased with increasing AD severity, whereas no difference was observed for systemic medication use. Positive associations between AD in the face and neck, and use of mild and moderately potent topical corticosteroids were observed, while involvement of palms and chest was associated with use of more potent topical corticosteroids. The mean DLQI, skin pain, and itch severity scores were lower in patients managed only with topical corticosteroids (5.5, 3.2, and 4.3, respectively) compared to patients treated with both oral and topical medication (7.1, 3.8, and 5.0, respectively). Patients with frequent topical corticosteroid use tended to be older (50.7 vs 48.6 years), males (50.0% vs 33.6%), current daily smokers (17.3% vs 13.7%), and having asthma (59.1% vs 43.8%) compared with infrequent users of topical corticosteroids. We found a disconnect between the severity of AD signs and symptoms, and use of AD therapies. In particular, a very modest use of systemic immunosuppressants was seen even among patients with severe AD symptoms. However, the underlying clinical decisions and reasons behind this disconnect is not clear based on the current data. [ABSTRACT FROM AUTHOR]

Aim: To examine whether adults with mild to moderate atopic dermatitis (AD) had reduced insulin sensitivity and/or exhibited other gluco-metabolic disturbances compared with carefully matched healthy controls. Materials and methods: Sixteen adult, non-obese, non-diabetic patients with mild to moderate AD and 16 gender-, age- and body mass index (BMI)-matched healthy controls underwent a hyperinsulinaemic euglycaemic clamp (insulin infusion rate: 40 mU/m²/minute) and an oral glucose tolerance test (OGTT) with frequent blood sampling for gut and pancreatic hormones. Results: The two groups were similar in age (33 ± 3 vs. 33 ± 3 years, mean ± standard error of the mean [SEM]), gender (56% women), BMI (24.5 ± 0.7 vs. 24.4 ± 0.7 kg/m²), physical activity level, fasting plasma glucose and HbA1c. Patients with AD had a mean Eczema Area and Severity Index score of 8.5 ± 1.0 (moderate disease) and a mean AD duration of 28 ± 3 years. During the OGTT, circulating glucose, insulin, C-peptide, glucagon and glucose-dependent insulinotropic polypeptide, respectively, were similar in the two groups, except glucagon-like peptide-1, which was higher in patients with AD. The clamp showed no differences in insulin sensitivity between groups (M-value 9.2 ± 0.6 vs. 9.8 ± 0.8, P = .541, 95% CI -1.51; 2.60), or circulating insulin, C-peptide and glucagon levels. Conclusions: Using OGTT and the hyperinsulinaemic euglycaemic clamp technique, we found no difference in insulin sensitivity or other gluco-metabolic characteristics between patients with mild to moderate AD and matched healthy controls, suggesting that the inflammatory skin disease AD has little or no influence on glucose metabolism. [ABSTRACT FROM AUTHOR]

Skin pain is a common and bothersome symptom of atopic dermatitis (AD) that is associated with a substantial burden. To assess the efficacy of abrocitinib vs. dupilumab on skin pain in patients with moderate-to-severe AD. Data from patients aged ≥18 years who received oral abrocitinib 200 mg once daily (QD) or subcutaneous dupilumab 300 mg once every 2 weeks in combination with topical therapy in the phase 3 trials JADE COMPARE (NCT03720470) and JADE DARE (NCT04345367) were analysed. Data from patients who received abrocitinib 100 mg QD or placebo in the JADE COMPARE trial were also included in this analysis. Patients rated their skin pain using the Skin Pain Numerical Rating Scale (NRS) item of the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) instrument ['How painful was your skin over the past 24 h?' on a scale from 0 (not painful) to 10 (extremely painful) ] in JADE COMPARE or the Skin Pain Numerical Rating Scale [SP-NRS, which queried patients for the severity of their 'worst skin pain' in the past 24 h on a scale from 0 (no skin pain) to 10 (worst skin pain imaginable)] in JADE DARE. Least squares mean (LSM) changes from baseline and proportions of patients who achieved a ≥4-point improvement from baseline in PSAAD skin pain score or SP-NRS were assessed through Week 16 (JADE COMPARE) or Week 26 (JADE DARE). The JADE COMPARE analysis (Skin Pain NRS item of the PSAAD) was performed post hoc, whereas the JADE DARE analysis (SP-NRS) was prespecified. At Week 2 of JADE COMPARE, LSM change from baseline in PSAAD skin pain score was greater with abrocitinib 200 mg [−2.8 (95% CI, −3.1, −2.5)] than with abrocitinib 100 mg [−2.1 (−2.3, −1.8)], dupilumab [−2.0 (−2.3, −1.8)], or placebo [−1.3 (−1.6, −0,9)]; improvements were sustained through Week 16 of treatment with abrocitinib 200 mg [−4.1 (−4.4, −3.8)], abrocitinib 100 mg [−3.3 (−3.6, −3.0)] and dupilumab [−4.0 (−4.2, −3.7)] compared with placebo [−1.8 (−2.2, −1.4)]. In JADE DARE, LSM change from baseline in SP-NRS was significantly greater with abrocitinib 200 mg vs. dupilumab at Week 2 [−3.7 (−3.9, −3.4) vs. −2.6 (−2.8, −2.3); P < 0.0001] and week 12 [−4.5 (−4.7, −4.2) vs. −4.0 (−4.3, −3.8); P = 0.0116]; no significant differences were observed between the treatment arms at Week 16 [−4.4 (−4.7, −4.2) vs. −4.2 (−4.4, −4.0); P = 0.16], Week 20 [−4.8 (−5.0, −4.5) vs. −4.5 (−4.7 vs. −4.2); P = 0.06] or Week 26 [−4.5 (−4.8, −4.3)] vs. −4.3 (−4.6, −4.1); P = 0.27]. The proportions of patients who achieved a ≥4-point improvement in PSAAD skin pain score at week 2 of JADE COMPARE were greater with abrocitinib 200 mg (43%) than with abrocitinib 100 mg (23%), dupilumab (24%) or placebo (14%). At Week 16, these proportions increased to 76% (abrocitinib 200 mg), 57% (abrocitinib 100 mg) and 70% (dupilumab) compared with placebo (29%). In JADE DARE, the proportions of patients who achieved a ≥4-point improvement in SP-NRS were significantly greater with abrocitinib 200 mg vs. dupilumab at Week 2 (58% vs. 36%; P < 0.0001) and Week 12 (71% vs. 61%; P = 0.0098) but not at subsequent timepoints. Similar to previous findings on the effect of abrocitinib on itch, these results suggest that abrocitinib 200 mg provides greater early skin pain relief in patients with moderate-to-severe AD compared with dupilumab, but the difference between the treatments diminishes with time. At earlier time points, skin pain improvement with abrocitinib 100 mg was similar to that with dupilumab. [ABSTRACT FROM AUTHOR]

There is a need for unified guidance on the management of ocular manifestations of atopic dermatitis and ocular manifestations associated with dupilumab in the Nordic region (Denmark, Finland, Norway and Sweden). This initiative gathered Nordic dermatologists and ophthalmologists to identify consensus in this area using a modified Delphi process. The initiative was led by a Nordic expert panel who developed a questionnaire that was circulated to a wider group. The results informed an agenda consisting of 24 statements to be voted on using a 5-point Likert scale at a meeting in Copenhagen on 24 April 2019. A facilitator moderated discussion and revised statements according to expert feedback for a second vote when required to reach consensus. Consensus was reached for 23 statements regarding the diagnosis, treatment and referral of these patients, which we hope will improve patient management in the Nordic region. [ABSTRACT FROM AUTHOR]

Occupational hand eczema is common among hairdressers, and protective gloves are important in limiting exposure to irritants and allergens. Various glove types may differ in their protective ability, and their use may lead to hand eczema due to skin irritancy and allergy. MEDLINE was searched for studies investigating permeation of gloves to irritants and allergens used in the hairdressing trade, as well as adverse effects of glove use affecting hairdressers. Forty‐four studies were identified; nine reported on permeation. Of those, two in vitro studies found nitrile rubber (NR) gloves to give the best protection when handling hair dyes. Polyethylene (PE) gloves had the lowest reported break‐through time. The prevalence of sensitization to rubber materials in European hairdressers was as follows: thiuram mix, median 2.5% (range 0%‐8.2%), weighted average 3.0% (95% confidence interval [CI] 3.0%‐3.1%); mercapto mix, median 0.4% (range 0%‐3.3%), weighted average 0.5% (95% CI 0.47%‐0.50%), mercaptobenzothiazole, median 0.6% (range 0%‐6.6%), weighted average 0.7% (95% CI 0.6%‐0.7%), NRL‐type I allergy, median 1.3% (range 1%‐16.4%), weighted average 4.0% (95% CI 3.6%‐4.5%). In conclusion, NR gloves provide the best skin protection for hairdressers, although natural rubber latex (NRL) and polyvinylchloride (PVC) gloves may be sufficient in most cases. PE gloves are not recommended. Synthetic rubber gloves with low or no levels of accelerators are preferred. [ABSTRACT FROM AUTHOR]

Background: Aluminum contact allergy is mostly seen in children with vaccination granulomas, following immunization with aluminum‐adsorbed childhood vaccines. Objectives: To characterize a cohort of children with vaccination granulomas and aluminum allergy concerning early life conditions, exacerbating factors, avoidance behavior, treatments, and potential impact on quality of life. Methods: A questionnaire study was conducted among 177 children aged 0 to 15 years with vaccination granulomas and aluminum allergy, and a reference group of 61 children aged 3 to 14 years with various types of dermatitis undergoing patch testing. Results: All children in the granuloma group were reportedly affected by itch. Infection exacerbated the itch in 59%. Other worsening factors were eating tin‐foiled/canned food (31%) and use of aluminum‐containing sunscreen (46%). Many parents took precautions to avoid aluminum exposure. Children with granulomas were more likely to be nonadherent to the National Vaccination Program than the reference group (27% vs 2%, P <.001). Parents in the granuloma group reported a decreased life quality for both parents and children compared with the reference group. Conclusions: Itching vaccination granulomas and aluminum allergy have a considerable negative impact on affected children and their families, causing avoidance behavior, reduced adherence to vaccination programs, and a negative effect on the overall life quality. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a prevalent inflammatory skin condition characterized by itch and dry skin, which affects 15-20% of children and 3-5% of adults. This article reviews epidemiological, clinical and experimental data to provide an overview of the most important disease mechanisms in atopic dermatitis. Genetic predisposition, environmental insults, atopic triggers, complex host immune response and skin barrier changes, and altered skin microbiota are discussed. Whilst our understanding of atopic dermatitis has improved dramatically in recent years, many basic aspects are still not understood. Further research is needed to fully understand this complex skin disease. [ABSTRACT FROM AUTHOR]

To the Editor, Atopic dermatitis (AD) is a prevalent inflammatory skin disease. The I FLG- i stratified analyses showed a trend toward cat exposure being a risk factor in children with I FLG i mutations and a protective factor in children without I FLG i mutations (Figure and Table S3). GLO:1X5/01jun20:all14162-fig-0001.jpg PHOTO (COLOR): Interaction between cat exposure and common FLG mutations in relation to (A) early-onset atopic dermatitis, (B) current atopic dermatitis, and (C) atopic dermatitis in the first 7 y of life gl We found no interaction between cat exposure in infancy and mutations in I FLG i on "early-onset AD" or "AD ever.". [Extracted from the article]

Similarities and differences in the everyday clinical management of moderate-to-severe atopic dermatitis in Nordic countries are unknown. Using a modified Delphi approach, 15 dermatologists from Denmark, Finland, Norway and Sweden completed face-to-face and online questionnaires and participated in summary discussions to map expert opinion on the clinical management of moderate-to-severe atopic dermatitis in these Nordic countries. Through discussions, 6 adult patient profiles, reflecting common disease presentations of atopic dermatitis, were identified. Using these case profiles, diagnostic work-up, treatment goals, patient education and treatment approaches were discussed. Patient education was identified as essential for effective management. A treatment sequence of moderateto- potent topical glucocorticosteroids and emollients, followed by systemic treatment, was recommended, allowing 3 months to ascertain systemic treatment response before switching, if necessary. Consensus was not reached on systemic treatment choice, reflecting differences in clinical practice and reimbursement between countries. Practical, case-based clinical recommendations were developed for optimal patient care. [ABSTRACT FROM AUTHOR]

Background: Hand eczema is a disease with large variation in clinical presentation and severity. Scoring systems for quantitative severity assessment exist. However, they are observer‐dependent. An objective quantitative tool for scoring of hand eczema would improve categorization of hand eczema. Objective: To investigate the usefulness of multispectral imaging in assessing severity of hand eczema with respect to extent and the different morphological features. Methods: Patients with hand eczema (n = 60) and healthy controls (n = 28) were included. The severity of hand eczema was assessed by a dermatologist using the Hand Eczema Severity Index (HECSI) and a global assessment (Physician Global Assessment [PGA]). Multispectral imaging of the hand was performed on all patients and controls using the VideometerLab Instrument. Results: Areas of the morphological elements identified by multispectral imaging were statistically significantly correlated with the PGA scores. Analyzed by Cohen's kappa, a moderate agreement between imaging‐based severity assessment and PGA was found. The imaging‐based severity assessment was also correlated with HECSI (Spearman rho 0.683, P < .001). Still, the imaging‐based algorithm was not capable of differentiating hand eczema patients from controls. Conclusions: Multispectral imaging allows quantitative measurements of different skin parameters to be performed. In its present form, multispectral imaging cannot replace the clinical assessment of a dermatologist. However, after refinement, this or similar technologies could prove useful. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) normally onsets in childhood and mostly resolves before adolescences. Disease persistence is known to be difficult to study properly, and current predictors are insufficient to identify more than a small fraction of patients at risk. Objective: To study personal AD medicine history as a retrospective marker of persistent AD. Methods: The study population included all Danish first hospital contacts with a diagnosis of AD (ICD‐10, L20) between 1995 and 2012. National register data following the diagnosis were used to define persistent AD activity until 2017 according to personal AD medicine history before diagnosis. Activity was defined as filled prescriptions for topical corticosteroids (TCS) or calcineurin inhibitors (TCI), dermatologist contacts or hospital re‐contacts for AD. Risk ratios (RR) for persistent activity (defined as activity >4 of the most recent 5 years) were estimated according to AD medicine history (prescriptions filled prior to diagnosis) adjusted for age at onset, parental AD and basic covariates. Results: A total of 13 628 patients were diagnosed at ages 0‐16 years and had up to 21 years of follow‐up. 10 years after diagnosis, 67% showed activity (9.5% persistent). Among prior TCS users (69%), the RR10y of persistent activity increased 1‐ to 6‐fold with increasing strength of strongest TCS/TCI ever, and with number of TCS courses. Prior use of antibiotics (RR10y 1.32, 95% CI 1.09‐1.59) and antihistamines (RR10y 1.65, 95% CI 1.42‐1.91) increased the RR10y in a dose‐dependent manner. In >90% of patients, prior medication use occurred <4 years before diagnosis. Conclusions and clinical relevance: The strength and type of AD medication used in the previous 4 years may predict 10‐year persistence of AD. Since children may be misjudged as having milder disease when seen between flares of skin lesions, this information may improve physicians' ability to determine the correct prognosis independently of current AD severity. [ABSTRACT FROM AUTHOR]

Nickel is the most frequent cause of contact allergy worldwide and has been studied extensively. This clinical review provides an updated overview of the epidemiology, exposure sources, methods for exposure quantification, skin deposition and penetration, immunology, diagnosis, thresholds for sensitization and elicitation, clinical pictures, prevention, and treatment. The implementation of a nickel regulation in Europe led to a decrease in the prevalence of nickel allergy, and changes in the clinical picture and disease severity. Nevertheless, the prevalences of nickel allergy in the European general population are approximately 8% to 19% in adults and 8% to 10% in children and adolescents, with a strong female predominance. Well‐known consumer items such as jewellery and metal in clothing are still the main causes of nickel allergy and dermatitis, although a wide range of items for both private and occupational use may cause dermatitis. Allergic nickel dermatitis may be localized to the nickel exposure site, be more widespread, or present as hand eczema. Today, efficient methods for exposure quantification exist, and new insights regarding associated risk factors and immunological mechanisms underlying the disease have been obtained. Nevertheless, questions remain in relation to the pathogenesis, the persistent high prevalence, and the treatment of severe cases. [ABSTRACT FROM AUTHOR]

Lebrikizumab (LEB) is a novel, high-affinity monoclonal anti - body that selectively binds to interleukin (IL)-13. To evaluate the efficacy and safety of LEB monotherapy in patients with moderate-to-severe atopic dermatitis (AD) in two identical phase 3 trials ADvocate1 (ADv1) and ADvocate2 (ADv2). Patients who responded to LEB 250 mg every 2 weeks (LEB Q2W) at the end of the 16-week induction period were re-randomized in a 2 : 2 :1 ratio to receive LEB Q2W, LEB 250 mg every 4 weeks (LEB Q4W) or placebo (LEB withdrawal) for an additional 36 weeks. Response, at week 16, was defined as achieving an IGA (0, 1) with a ≥2-point improvement or EASI75 and no use of rescue medication. Efficacy outcomes reported at week 52 included IGA (0, 1), EASI 75, ≥4-point reduction in Pruritis Numeric Rating Scale (NRS), EASI 90 and DLQI ≥4-point. Safety analysis was conducted on all patients who received ≥1 dose of LEB. Patients maintained IGA (0, 1) in LEB Q2W (ADv1, 75.8%; ADv2, 64.6%), LEB Q4W (ADv1, 74.2%; ADv2, 80.6%) and LEB withdrawal (ADv1, 46.5%; ADv2, 49.8%). Maintenance of EASI75 was, in LEB Q2W (ADv1, 79.2%; ADv2, 77.4%), LEB Q4W (ADv1, 79.2%; ADv2, 84.7%) and LEB withdrawal (ADv1, 61.3%; ADv2, 72.0%). For Pruritus NRS ≥4-point improvement from baseline, patients-maintained improvement in the LEB Q2W (ADv1, 81.2%; ADv2, 90.3%), LEB Q4W (ADv1, 80.4%; ADv2, 88.1%) and LEB withdrawal (ADv1, 65.4%; ADv2, 67.6%). Maintenance of EASI90 was, in LEB Q2W (ADv1, 66.1%; ADv2, 61.5%), LEB Q4W (ADv1, 66.6%; ADv2, 67.4%) and LEB withdrawal (ADv1, 45.5%; ADv2, 36.9%). DLQI ≥4-point improvement from baseline was LEB Q2W (ADv1, 64.0%; ADv2, 59.0%), LEB Q4W (ADv1, 62.7%; ADv2, 73.0%) and LEB withdrawal (ADv1, 57.7%; ADv2, 45.5%). TEAEs were reported by 58.1% (ADv1) and 67.8% (ADv2) LEB-treated patients at week 52. Serious adverse events were reported by 3.3% of ADv1 patients and 2.7% of ADv2 patients. In ADv1 and ADv2, 2.3% and 3.9% of patients reported an adverse event leading to treatment discontinuation, respectively. Both LEB Q2W and LEB Q4W maintained improvement in all reported outcomes for the treatment of moderate-to-severe AD through 52 weeks. The safety profile was consistent with previously published data. [ABSTRACT FROM AUTHOR]

Abstract: Skin diseases represent one of the most common work‐related diseases and may have a detrimental effect on social, personal and occupational aspects of life. Contact dermatitis (CD), which comprises predominately irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD), accounts for vast majority of occupational skin diseases, especially in occupations associated with frequent skin contact with irritants and contact allergens. Although ICD and ACD have similar clinical manifestation, their pathophysiology and the role of the skin barrier are different. In ICD, perturbation of the skin barrier is the primary event which sets into motion diverse metabolic processes and triggers activation of innate immunity without the involvement of adaptive immune system. In ACD, a type IV hypersensitivity reaction induced by contact allergens, the skin barrier impairment may evoke innate signalling pathways during the sensitization phase required for the activation of T‐cell adaptive response. Thus, skin barrier impairment may increase the risk of ICD or ACD not only because of enhanced permeability and ingress of irritants and allergens but also by the generation of innate immune signal needed for the induction of allergic response. Hence, an efficient way to prevent CD is to avoid skin barrier damage in the workplace. This review focuses on the skin barrier, how it is affected by skin irritants and how its impairment contributes to the development of ICD and ACD. [ABSTRACT FROM AUTHOR]

Studies examining the association between type 1 diabetes (T1D) and atopic diseases, i.e., atopic dermatitis, allergic rhinitis and asthma have yielded conflicting results due to different algorithms for classification, sample size issues and risk of referral bias of exposed cohorts with frequent contact to health care professionals. Using Danish national registries and well-established disease algorithms, we examined the bidirectional association between T1D and atopic diseases in childhood and adolescence using Cox Proportional Hazard regression compared to two different unexposed cohorts from a population of 1.5 million Danish children born from 1997 to 2018. We found no associations between T1D and atopic dermatitis, allergic rhinitis, or asthma (defined after age five). However, in multivariable analysis we found an increased risk of persistent wheezing (defined as asthma medication before age five) after T1D with an adjusted hazard ratio (aHR) of 1.70 [1.17–2.45]. We also identified an increased risk of developing T1D after persistent wheezing with aHR of 1.24 [1.13–1.36]. This study highlights similar risks of atopic diseases in children with T1D and of T1D in children with atopic disease after age of five years versus healthy controls. However, more research is needed to understand the possible early immunological effects of the link between persistent wheezing and T1D. [ABSTRACT FROM AUTHOR]

This study examined trends in prevalence of HEMA allergy as well as the characteristics of patients with contact allergy to HEMA. Because there was only one male patient with contact allergy to HEMA during the study period, we studied all female patients who were patch tested with HEMA between January 1, 2017 and July 1, 2019. GLO:FQV/01apr20:cod13439-fig-0001.jpg PHOTO (COLOR): A history of using UV nail polish in patch test HEMA-positive and HEMA-negative patients. [Extracted from the article]

Nickel contact allergy remains a problem in EU countries, despite the EU Nickel Directive. To study the prevalence of nickel allergy in EU countries following the implementation of the EU Nickel Directive, we performed a systematic search in PubMed for studies that examined the prevalence of nickel allergy in EU countries published during 2005-2016. We identified 46 studies: 10 in the general population and 36 in patch tested dermatitis patients. A significantly lower prevalence of nickel allergy after than before the implementation of the EU Nickel Directive was found in women aged 18-35 years (11.4% versus 19.8%) ( p = 0.02), in female dermatitis patients aged ≤17 years (14.3% versus 29.2%) ( p < 0.0001), and in dermatitis patients aged 18-30 years (women: 20.2% versus 36.6%) ( p < 0.0001) (men: 4.9% versus 6.6%) ( p < 0.0001). Overall, the prevalence was higher in southern than in northern EU countries, and generally remained high, affecting 8-18% of the general population. A consistent pattern of decreasing prevalence of nickel allergy in some EU countries was observed, although the prevalence among young women remains high. Steps should be taken for better prevention of nickel allergy in EU countries. [ABSTRACT FROM AUTHOR]

Psoriasis has been associated with increased risk of myocardial infarction (MI) in some, but not all, studies. This study investigated the risk of MI in patients with psoriasis and psoriatic arthritis in Denmark. All residents aged =18 years from 1 January 2008 through 31 December 2012 were included. Adjusted hazard ratios (HRs) did not show an increased risk of MI in patients with mild psoriasis (HR 1.02; 95% confidence interval (95% CI) 0.96-1.09), whereas the risk was slightly increased in patients with severe psoriasis (HR 1.21; 1.07-1.37). Stratified by age, there was no increased risk of MI in any specific age group, regardless of severity. Limited to first-time MI, the risk was increased only in patients with severe psoriasis aged <50 years (HR 1.52; 1.03-2.25). The same applied to patients without psoriatic arthritis (severe psoriasis aged <50 years; HR 1.74; 1.11-2.72). In analyses restricted to patients with psoriatic arthritis, age-specific strata did not show any association between psoriatic arthritis and MI risk. [ABSTRACT FROM AUTHOR]

Epidermal filaggrin level is affected by ultraviolet B irradiation in animal and experimental models. This study examined the effect of ultraviolet B irradiation on epidermal filaggrin and natural moisturizing factors in vivo in healthy adults (n = 22). Participants were irradiated with 2 minimal erythema doses of ultraviolet B on the skin. Biopsies and tape strips were collected from skin irradiated 24 and 72 h earlier and from nonirradiated skin (control). Real-time quantitative PCR on skin biopsies showed significantly reduced profilaggrin mRNA expression 24 h after irradiation (mean relative mRNA expression ± standard deviation: control, 3.86 ± 2.06 vs. 24 h, 1.52 ± 0.640; p = 0.02; n = 8). Immunohistochemistry showed aberrant spatial distribution of filaggrin protein 72 h after irradiation (n = 3). High-pressure liquid chromatography of tape extracts showed no change in mean total natural moisturizing factor levels after irradiation, but mean trans-urocanic acid was significantly reduced, as expected (n = 8). In conclusion, erythemal doses of ultraviolet B exert acute effects on profilaggrin mRNA and filaggrin protein in human skin in vivo. [ABSTRACT FROM AUTHOR]

Background Chromium coatings on metal alloys can be decorative, and prevent corrosion and metal ion release. We recently showed that handling of a chromium-containing disc resulted in chromium deposition on the skin. Objectives To examine patch test reactivity to chromium-coated discs. Methods We included 15 patients: 10 chromium-allergic patients, and 5 patients without chromium allergy. All were patch tested with potassium dichromate, cobalt chloride, nickel sulfate, and nine different metallic discs. The chromium-allergic patients were also patch tested with serial dilutions of potassium dichromate. Results Positive/weaker reactions were observed to disc B (1 of 10), disc C (1 of 10), and disc D, disc E, and disc I (4 of 10 each). As no controls reacted to any of the discs, the weak reactions indicate allergic reactions. Positive patch test reactions to 1770 ppm chromium(VI) in the serial dilutions of potassium dichromate were observed in 7 of 10 patients. When the case group was narrowed down to include only the patients with a current positive patch test reaction to potassium dichromate, elicitation of dermatitis by both chromium(III) and chromium(VI) discs was observed in 4 of 7 of patients. Conclusions Many of the patients reacted to both chromium(III) and chromium(VI) surfaces. Our results indicate that both chromium(VI) and chromium(III) pose a risk to chromium-allergic patients. [ABSTRACT FROM AUTHOR]

Background Information concerning health-related quality of life ( HRQoL) and comorbidities of adult dermatitis patients stratified by loss-of-function mutations in the filaggrin gene ( FLG) is limited. Objective To investigate HRQoL, skin symptoms and comorbidities in adult FLG mutation carriers. Methods This cross-sectional study included patients diagnosed with atopic dermatitis and/or hand eczema (n = 520). Patients completed questionnaires about dermatitis, skin symptoms, HRQoL, and comorbidities, including actinic keratosis, and atopic and mental disorders. Results FLG mutations ( R501X, 2282del4, and R2447X) were identified in 16.9% of patients, and were significantly associated not only with atopic dermatitis, but also independently with skin fissures on the fingers and heels, and self-reported actinic keratosis. Although FLG mutations were significantly associated with reduced HRQoL, as measured by use of the Dermatology Life Quality Index ( DLQI), no association with self-reported anxiety or depression was identified. Notably, the highest median DLQI score, reflecting greater impairment, was reported by patients with both FLG mutations and atopic dermatitis. Overall, 19.7% of patients with both atopic dermatitis and FLG mutations reported a 'large or extremely large' impact on their lives; this represents twice the prevalence seen in patients with atopic dermatitis and wild-type FLG (9.6%). Conclusion Patients with both atopic dermatitis and common FLG mutations are more frequently affected by reduced HRQoL. [ABSTRACT FROM AUTHOR]