Search

IMPORTANCE: Treatment of erythema and flushing in rosacea is challenging. Calcitonin gene-related peptide (CGRP) has been associated with the pathogenesis of rosacea, raising the possibility that inhibition of the CGRP pathway might improve certain features of the disease. OBJECTIVE: To examine the effectiveness, tolerability, and safety of erenumab, an anti–CGRP-receptor monoclonal antibody, for the treatment of rosacea-associated erythema and flushing. DESIGN, SETTING, AND PARTICIPANTS: This single-center, open-label, single-group, nonrandomized controlled trial was conducted between June 9, 2020, and May 11, 2021. Eligible participants included adults with rosacea with at least 15 days of either moderate to severe erythema and/or moderate to extreme flushing. No concomitant rosacea treatment was allowed throughout the study period. Visits took place at the Danish Headache Center, Copenhagen University Hospital, Rigshospitalet in Copenhagen, Denmark. Participants received 140 mg of erenumab subcutaneously every 4 weeks for 12 weeks. A safety follow-up visit was performed at week 20. Data analysis occurred from January 2023 to January 2024. INTERVENTION: 140 mg of erenumab every 4 weeks for 12 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was mean change in the number of days with moderate to extreme flushing during weeks 9 through 12, compared with the 4-week run-in period (baseline). The mean change in number of days with moderate to severe erythema was a secondary outcome. Adverse events were recorded for participants who received at least 1 dose of erenumab. Differences in means were calculated with a paired t test. RESULTS: A total of 30 participants (mean [SD] age, 38.8 [13.1] years; 23 female [77%]; 7 male [23%]) were included, of whom 27 completed the 12-week study. The mean (SD) number of days with moderate to extreme flushing was reduced by −6.9 days (95% CI, −10.4 to −3.4 days; P < .001) from 23.6 (5.8) days at baseline. The mean (SD) number of days with moderate to severe erythema was reduced by −8.1 days (95% CI, −12.5 to −3.7 days; P < .001) from 15.2 (9.1) days at baseline. Adverse events included transient mild to moderate constipation (10 participants [33%]), transient worsening of flushing (4 participants [13%]), bloating (3 participants [10%]), and upper respiratory tract infections (3 participants [10%]), consistent with previous data. One participant discontinued the study due to a serious adverse event (hospital admission due to gallstones deemed unrelated to the study), and 2 participants withdrew consent due to lack of time. CONCLUSIONS AND RELEVANCE: These findings suggest that erenumab might be effective in reducing rosacea-associated flushing and chronic erythema (participants generally tolerated the treatment well, which was consistent with previous data), and that CGRP-receptor inhibition holds potential in the treatment of erythema and flushing associated with rosacea. Larger randomized clinical trials are needed to confirm this finding. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04419259

Background Psoriatic arthritis (PsA) is a prevalent comorbidity among patients with psoriasis, heavily contributing to their burden of disease, usually diagnosed several years after the diagnosis of psoriasis.Objectives To investigate the predictability of psoriatic arthritis in patients with psoriasis and to identify important predictors.Methods Data from the Swiss Dermatology Network on Targeted Therapies (SDNTT) involving patients treated for psoriasis were utilized. A combination of gradient-boosted decision trees and mixed models was used to classify patients based on their diagnosis of PsA or its absence. The variables with the highest predictive power were identified. Time to PsA diagnosis was visualized with the Kaplan-Meier method and the relationship between severity of psoriasis and PsA was explored through quantile regression.Results A diagnosis of psoriatic arthritis was registered at baseline of 407 (29.5%) treatment series. 516 patients had no registration of PsA, 257 patients had PsA at inclusion, and 91 patients were diagnosed with PsA after inclusion. The model’s AUROCs was up to 73.7%, and variables with the highest discriminatory power were age, PASI, physical well-being, and severity of nail psoriasis. Among patients who developed PsA after inclusion, significantly more first treatment series were classified in the PsA-group, compared to those with no PsA registration. PASI was significantly correlated with the median burden/severity of PsA (P= .01).Conclusions Distinguishing between patients with and without PsA based on clinical characteristics is feasible and even predicting future diagnoses of PsA is possible. Patients at higher risk can be identified using important predictors of PsA.

Topical corticosteroids (TCS) are used to treat most patients with chronic hand eczema (CHE), but knowledge about TCS-related adverse events in CHE is limited.

IMPORTANCE: Atopic dermatitis onset usually occurs in childhood. Persistence of disease into adolescence and adulthood is common. It is important to evaluate new treatment options in adolescents because of the high unmet need in this population. OBJECTIVE: To assess the efficacy and safety of upadacitinib to treat moderate-to-severe atopic dermatitis in adolescents. DESIGN, SETTING, AND PARTICIPANTS: Prespecified analysis of adolescents enrolled in 3 randomized, double-blind, placebo-controlled phase 3 clinical trials in more than 20 countries across Europe, North and South America, Oceania, the Middle East, and the Asia-Pacific region from July 2018 through December 2020. Participants were adolescents aged 12 to 17 years with moderate-to-severe atopic dermatitis. Data analysis was performed from April to August 2021. INTERVENTIONS: Patients were randomized (1:1:1) to once-daily oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo alone (Measure Up 1 and Measure Up 2) or with topical corticosteroids (AD Up). MAIN OUTCOMES AND MEASURES: Safety and efficacy, including at least a 75% improvement in the Eczema Area and Severity Index from baseline and validated Investigator Global Assessment for Atopic Dermatitis score of 0 (clear) or 1 (almost clear) at week 16 (coprimary end points). RESULTS: A total of 552 adolescents (290 female; 262 male) were randomized. Mean (SD) age was 15.4 (1.8), 15.5 (1.7), and 15.3 (1.8) years for adolescents in Measure Up 1, Measure Up 2, and AD Up, respectively. In Measure Up 1, Measure Up 2, and AD Up, respectively, a greater proportion of adolescents (% [95% CI]) achieved at least 75% improvement in the Eczema Area and Severity Index at week 16 with upadacitinib 15 mg (73% [63%-84%], 69% [57%-81%], 63% [51%-76%]), and upadacitinib 30 mg (78% [68%-88%], 73% [62%-85%], 84% [75%-94%]), than with placebo (12% [4%-20%], 13% [5%-22%], 30% [19%-42%]; nominal P < .001 for all comparisons vs placebo). Similarly, a greater proportion of adolescents treated with upadacitinib achieved a validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 at week 16 and improvements in quality of life with upadacitinib than with placebo. Upadacitinib was generally well tolerated in adolescents. Acne was the most common adverse event, and all acne events were mild or moderate. CONCLUSIONS AND RELEVANCE: In this analysis of 3 randomized clinical trials, upadacitinib was an effective treatment for adolescents with moderate-to-severe atopic dermatitis, with an acceptable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2), and NCT03568318 (AD Up)

IMPORTANCE: Identifying the optimal long-term biologic therapy for patients with psoriasis is often done through trial and error. OBJECTIVE: To identify the optimal biologic therapy for individual patients with psoriasis using predictive statistical and machine learning models. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used data from Danish nationwide registries, primarily DERMBIO, and included adult patients treated for moderate-to-severe psoriasis with biologics. Data were processed and analyzed between spring 2021 and spring 2022. MAIN OUTCOMES AND MEASURES: Patient clusters of clinical relevance were identified and their success rates estimated for each drug. Furthermore, predictive prognostic models to identify optimal biologic treatment at the individual level based on data from nationwide registries were evaluated. RESULTS: Assuming a success criterion of 3 years of sustained treatment, this study included 2034 patients with a total of 3452 treatment series. Most treatment series involved male patients (2147 [62.2%]) originating from Denmark (3190 [92.4%]), and 2414 (69.9%) had finished an education longer than primary school. The average ages were 24.9 years at psoriasis diagnosis and 45.5 years at initiation of biologic therapy. Gradient-boosted decision trees and logistic regression were able to predict a specific cytokine target (eg, interleukin-17 inhibition) associated with a successful treatment with accuracies of 63.6% and 59.2%, and top 2 accuracies of 95.9% and 93.9%. When predicting specific drugs resulting in success, gradient boost and logistic regression had accuracies of 48.5% and 44.4%, top 2 accuracies of 77.6% and 75.9%, and top 3 accuracies of 89.9% and 89.0%. CONCLUSIONS AND RELEVANCE: Of the treatment prediction models used in this cohort study of patients with psoriasis, gradient-boosted decision trees performed significantly better than logistic regression when predicting specific biologic therapy (by drug as well as target) leading to a treatment duration of at least 3 years without discontinuation. Predicting the optimal biologic could benefit patients and clinicians by minimizing the number of failed treatment attempts.

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.

IMPORTANCE: Four distinct rosacea subtypes have traditionally been recognized, but the frequency of these subtypes among patients with rosacea remains unknown. OBJECTIVE: To assess the frequency of 4 rosacea subtypes. DATA SOURCES: This systemic review and meta-analysis included a search of 2 databases, PubMed and Embase, from inception of the databases to November 2, 2021. The search was filtered to include only studies of human participants published in English, French, and German. STUDY SELECTION: Studies were screened independently by 2 of the authors and were included if they were original with a sample size of 25 or more patients and reported absolute numbers or frequency of patients affected by rosacea subtypes. Studies that did not report sufficient data to calculate the proportions of subtypes were excluded. DATA EXTRACTION AND SYNTHESIS: Data extraction was performed independently and in duplicate by 2 of the authors, using the search term rosacea, according to the Preferred Reporting items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The search term, objectives, and study protocol methods were defined before the study was initiated. A total of 292 studies were included for full-text assessment. Owing to the heterogeneity of the included studies, a random-effects model was used. MAIN OUTCOME AND MEASURES: The main outcome was the proportion of patients with rosacea in each of the 4 major subtype groups defined by the 2002 National Rosacea Society classification system. Measures were absolute numbers or frequency of patients affected by each of the 4 rosacea subtypes. RESULTS: A total of 39 studies examining 9190 patients with rosacea were included. The pooled proportion of erythematotelangiectatic rosacea was 56.7% (95% CI, 51.4%-62.0%), of papulopustular rosacea was 43.2% (95% CI, 38.8%-47.6%), of phymatous rosacea was 7.4% (95% CI, 6.1%-8.9%), and of ocular rosacea was 11.1% (95% CI, 6.7%-16.3%). Subtype distribution occurred equally among men and women except for phymatous rosacea, which was more prevalent in men. Studies from Africa showed the lowest proportion of erythematotelangiectatic rosacea. Differences in frequency of subtypes were observed when stratification by publication year was performed. CONCLUSION AND RELEVANCE: In this systematic review and meta-analysis, differences were found in rosacea subtypes by patient sex and by continent of origin and publication year of included studies. Erythematotelangiectatic and papulopustular rosacea were the most prevalent subtypes, but data should be interpreted with caution. Future studies should use the phenotype-based rosacea approach.

IMPORTANCE: Primary results from the Measure Up 1 and Measure Up 2 studies demonstrated upadacitinib efficacy and safety through 16 weeks in patients with atopic dermatitis. Longer-term outcomes remain unknown. OBJECTIVE: To evaluate long-term (52 weeks) efficacy and safety of upadacitinib treatment in patients with atopic dermatitis. DESIGN, SETTING, AND PARTICIPANTS: Measure Up 1 and Measure Up 2 are ongoing double-blind, placebo-controlled, replicate phase 3 randomized clinical trials that include adults and adolescents with moderate to severe atopic dermatitis at 151 and 154 centers, respectively. Cutoffs for this analysis were December 21, 2020 (Measure Up 1), and January 15, 2021 (Measure Up 2). INTERVENTIONS: Patients were randomized 1:1:1 to receive once-daily oral upadacitinib 15 mg, 30 mg, or placebo. At week 16, patients randomized at baseline to receive upadacitinib 15 mg (273 and 260 patients in Measure Up 1 and Measure Up 2, respectively) and 30 mg (270 and 268 patients) continued assigned treatment; placebo-treated patients were rerandomized 1:1 to receive upadacitinib 15 mg (121 and 120 patients in Measure Up 1 and Measure Up 2, respectively) or 30 mg (123 and 121 patients) in a double-blinded manner. MAIN OUTCOMES AND MEASURES: Safety and efficacy, including 75% improvement in the Eczema Area and Severity Index and Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or greater grades of improvement, were assessed. RESULTS: Measure Up 1 and Measure Up 2 included a total of 1609 patients (mean [SD] age, 33.8 [15.6] years; 727 women [45.2%]; 882 men [54.8%]). Efficacy at week 16 was maintained through week 52. At week 52, 75% improvement in the Eczema Area and Severity Index was achieved by 82.0% (95% CI, 77.0%-86.9%) and 79.1% (95% CI, 73.9%-84.4%) of patients continuing the 15-mg dose and 84.9% (95% CI, 80.3%-89.5%) and 84.3% (95% CI, 79.6%-89.0%) of patients continuing the 30-mg dose (for Measure Up 1 and Measure Up 2, respectively); Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or greater grades of improvement was achieved by 59.2% (95% CI, 52.9%-65.5%) and 52.6% (95% CI, 46.2%-59.1%) and 62.5% (95% CI, 56.3%-68.7%) and 65.1% (95% CI, 58.9%-71.2%) of patients in the Measure Up 1 and Measure Up 2 studies, respectively. Treatment discontinuation due to adverse events was low overall but was slightly higher for the upadacitinib 30-mg dose. Both upadacitinib doses were well tolerated with no new safety signals. CONCLUSIONS AND RELEVANCE: In this analysis of follow-up data from 2 randomized clinical trials, longer-term treatment of adolescents and adults with moderate to severe atopic dermatitis with upadacitinib demonstrated a favorable benefit-risk profile, with sustained efficacy responses through 52 weeks. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1) and NCT03607422 (Measure Up 2)

The psychometric validity and reliability of widely used atopic dermatitis (AD) outcome measures across different races and ethnicities are unclear. We describe the rates of reporting race, ethnicity, and skin tone in studies testing the psychometric properties of AD outcome measures and compare the psychometric analyses across race, ethnicity, and skin tone. We systematically reviewed MEDLINE and EMBASE for studies reporting psychometric properties of clinician-reported or patient-reported outcome measures in AD (International Prospective Register of Systematic Reviews: CRD42021239614). Overall, 16,100 nonduplicate articles were screened; 165 met inclusion criteria. Race and/or ethnicity were reported in 55 (33.3%) studies; of those, race was assessed by self-report in 10 studies (6.1%) or was unspecified in 45 (27.3%). A total of 16 studies (9.7%) evaluated psychometric property differences by race, and only five (4.4%) of those did not recognize it as a limitation. Properties assessed across race, ethnicity, or skin tone were differential item functioning, convergent validity feasibility, inter-rater reliability, intrarater reliability, test‒retest reliability, and known-groups validity. Multiple instruments demonstrated performance differences across ethnoracial groups. This review highlights the paucity of race/ethnicity consideration for psychometric property testing in AD outcome measurement instruments. More AD outcomes instruments should be validated in diverse populations.

IMPORTANCE: Biologics are important in treating patients with hidradenitis suppurativa (HS). However, to our knowledge, data on their real-life performance and treatment patterns in HS are limited. OBJECTIVE: To examine the drug survival of biologic therapies for HS in a real-world setting. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included all patients with HS between January 1, 2005, and December 31, 2018, who were treated with biologics at the 5 academic hospital clinics where all biologic treatment for HS is conducted in Denmark. Biologics included adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, secukinumab, and ustekinumab. Data were analyzed between June 1, 2021, and June 20, 2021. MAIN OUTCOMES AND MEASURES: Drug survival was depicted through Kaplan-Meier curves, and Cox regression models were used to calculate adjusted (age, sex, previous number of biologic treatment series) hazard ratios (aHRs) with 95% CIs for the risk of treatment discontinuation. Switching patterns were visualized through a Sankey diagram. RESULTS: The study comprised 241 patients (176 women [61.8%]; total of 386 treatment series) with a mean (SD) age of 41.8 (12.6) years at initiation of first biologic therapy. There were a total of 256 (189 [73.8%] biologic naive), 66 (32 [48.5%] biologic naive), 23 (9 [39.1%] biologic naive), and 22 (9 [40.9%] biologic naive) treatment series with adalimumab, infliximab, etanercept, and ustekinumab, respectively. The median time to discontinuation was 36.0 (IQR, 21.9-63.0), 28.7 (IQR, 15.1-62.9), 26.0 (IQR, 16.9-155.9), and 17.9 weeks (IQR, 12.9-41.0) for adalimumab, infliximab, ustekinumab and etanercept, respectively. The risk of drug discontinuation was significantly higher for etanercept compared with adalimumab (aHR, 1.81; 95% CI, 1.16-2.82), infliximab (aHR, 1.77; 95% CI, 1.03-3.05), and ustekinumab (aHR, 2.49; 95% CI, 1.12-5.52), whereas no difference was observed when comparing these 3 therapies with each other. We found no significant differences in drug survival for biologic-naive vs nonnaive treatment series. Increasing C-reactive protein levels (aHR, 1.01; 95% CI, 1.00-1.03) and concomitant antibiotic treatment (aHR, 2.82; 95% CI, 1.36-5.86) were associated with the risk of discontinuing infliximab therapy. Men (aHR, 0.69; 95% CI, 0.51-0.91) had a reduced risk of discontinuing use of adalimumab. CONCLUSIONS AND RELEVANCE: In this cohort study, drug survival was comparable between adalimumab, infliximab, and ustekinumab but significantly lower for etanercept. There were no differences in drug survival among biologic-naive and nonnaive patients.

BackgroundOccupational hand eczema (OHE) is common in hairdressers, and many leave the trade because of the disease. However, the exact impact of OHE on career length is unknown.ObjectiveTo assess the effect of OHE on career length and risk factors associated with leaving the trade because of OHE in hairdressers followed-up for up to 35 years.MethodsA prospective cohort study of Danish hairdressers graduating between 1985 and 2007 (n=5219) was performed. A questionnaire was sent in 2009 and 2020. The Danish Labor Marked Supplementary Pension Scheme provided information on affiliation to the hairdressing profession. Career length was assessed by Kaplan-Meier analyses.ResultsThe median survival time was 12.0 (95% CI 11.0 to 13.0) years in graduates with OHE and 14.0 (95% CI 12.6 to 15.4) years in graduates without OHE (p<0.001). Graduates with a frequency of hand eczema (HE) of ‘once’, ‘several times’ and ‘almost all the time’ had a median survival time of 20.0 (95% CI 14.6 to 25.4), 12.0 (95% CI 10.7 to 13.3) and 7.0 (95% CI 5.6 to 8.4) years, respectively. Graduates with OHE that left the trade (partly) because of HE constituted 11.7% of the study population. Factors associated with leaving the trade because of HE included a history of atopic dermatitis (adjusted OR (aOR) 2.2 (95% CI 1.2 to 4.0), a history of a positive patch test (aOR 5.1 (95% CI 2.3 to 11.0) and allergy to hair dyes (aOR 9.4 (95% CI 3.4 to 25.6).ConclusionCareer length is reduced in hairdressers with OHE, especially if frequently relapsing or caused by contact allergy, for example, to hair dyes.

Wir stellen 2 Fälle von Rosazea vor, die erfolgreich mit einer Off-Label-Therapie behandelt wurden. Bei dem ersten Fall handelt es sich um schmerzhafte, exsudierende papulopustulöse Läsionen der Nase, die mit Rifaximin behandelt wurden, und bei dem anderen Fall handelt es sich um schwere, belastende und schmerzhafte Hautrötungen, die mit Sumatriptan behandelt wurden. Die Fälle stützen frühere Annahmen, dass gastrointestinale Komorbiditäten möglicherweise mit papulopustulären Läsionen in Zusammenhang stehen und dass Rötungen mit neurogenen Entzündungen und Migräne in Verbindung stehen können. Die Fälle deuten zudem darauf hin, dass ein neuer Ansatz für die Behandlung von Rosazea auf der Grundlage von Endotypen und Komorbiditäten erforderlich sein könnte.

Purpose of Review: It is still debated whether the risk of allergic contact dermatitis (ACD) is altered in patients with atopic dermatitis (AD). In this article, the recent literature on the risk of ACD in AD patients is reviewed and put into a clinical context. Recent Findings: ACD is common in AD patients, but a literature review showed conflicting results on the exact risk compared to non-AD individuals. The development of ACD in AD patients is affected by the dysfunctional skin barrier in particular due to filaggrin deficiency, the Th2 inflammatory immune dysregulation, and microbial dysbiosis. While the increased exposure to topical allergens in AD patients increases the risk of ACD in AD, the Th2-skewed immune response observed in AD reduces the risk of ACD in a severity-dependent manner. Summary: ACD should be considered in AD patients with eczema worsening, or atypical morphology and generalization despite relevant treatment. Special attention should be paid to the increased risk of ACD to allergens found in topical products.

IMPORTANCE: Questionnaire studies are important for estimating the prevalence of psoriasis and atopic dermatitis; however, validity among the adult population remains an important concern. OBJECTIVE: To examine the test-retest accuracy of questionnaires for measuring psoriasis and atopic dermatitis prevalence in an adult population. DESIGN, SETTING, AND PARTICIPANTS: This nationwide population-based cohort study administered questionnaires on psoriasis and atopic dermatitis to the same 2333 and 2312 randomly selected adults (≥18 years) in Denmark, respectively, at 2 different time points from May 15, 2018, to November 20, 2020. Data were analyzed from January 10 to January 28, 2021. To reduce the risk of participation bias, potential respondents were given information on the research project only after agreeing to participate. EXPOSURES: Participants were asked identical questions on psoriasis and atopic dermatitis in 2018 and in 2020. Responses were linked at the individual-level. MAIN OUTCOMES AND MEASURES: The test-retest reliability (expressed by Cohen κ). RESULTS: The psoriasis questionnaire was completed by 2333 (mean [SD] age, 55.1 [16.2] years; 1338 [57.4%] women) participants in 2018 and in 2020. The atopic dermatitis questionnaire was completed by 2312 (mean [SD] age, 55.0 [16.2] years; 1326 [57.4%] women) participants in 2018 and in 2020. Among participants reporting a history of psoriasis, agreement between individual responses was high (κ = 0.7558); however, among those reporting a history of atopic dermatitis, agreement was low (κ = 0.4395). For psoriasis, prevalence changed from 7.8% to 8.0%; for atopic dermatitis, from 8.2% to 7.6%. Of participants who in 2018 reported dermatologist-diagnosed atopic dermatitis, 36.9% claimed in the 2020 questionnaire that they had never had atopic dermatitis. Analyses revealed substantial agreement for psoriasis responses across all age strata; for atopic dermatitis responses, the κ declined with increasing age, to 0.2613 for participants 65 or older. CONCLUSIONS AND RELEVANCE: This cohort study found considerable agreement between responses over time when participants were asked about a history of psoriasis. When asked about a history of atopic dermatitis, responses over time were inconsistent. This inconsistency suggests that questionnaires on a history of atopic dermatitis will confer considerable risk of bias and misclassification.

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by intense pruritus and recurrent eczematous lesions that significantly impair quality of life. It is a heterogeneous disease affecting both children and adults. The treatment of moderate-to-severe forms of AD is challenging, as topical corticosteroids are often insufficient to achieve disease control or inappropriate and off-label use of immunosuppressants may have significant undesirable side effects. The development of targeted biologic therapies specifically for AD is thus highly desirable. Dupilumab is the only biologic therapy that is Food and Drug Administration approved for the treatment of moderate-to-severe AD in patients 6 years and older, with consistent long-term efficacy and safety trial data. In this article, we review the mechanisms, safety, and efficacy of dupilumab from recent clinical trials, and we review the current data, mechanism of action, clinical efficacy, and limitations of new biologics currently in phase 2 and 3 clinical trials (lebrikizumab, tralokinumab, nemolizumab, tezepelumab, and ISB 830).

IMPORTANCE: Systemic and inhaled corticosteroids negatively affect bone remodeling and cause osteoporosis and bone fracture when given continuously or in high doses. However, risk of osteoporosis and major osteoporotic fracture (MOF) after application of topical corticosteroids (TCSs) is largely unexplored. OBJECTIVE: To examine the association between cumulative exposure to potent and very potent TCSs and risk of osteoporosis and MOF. DESIGN, SETTING, AND PARTICIPANTS: This nationwide retrospective cohort study included 723 251 Danish adults treated with potent or very potent TCSs from January 1, 2003, to December 31, 2017. Data were obtained from Danish nationwide registries. Filled prescription data were converted in equipotent doses to mometasone furoate (1 mg/g). Data were analyzed from June 1 to August 31, 2019. EXPOSURES: Patients were considered exposed when they had filled prescriptions of cumulative amounts corresponding to the equivalent of at least 500 g of mometasone, using filled prescriptions of 200 to 499 g as the reference group. MAIN OUTCOMES AND MEASURES: The co-primary outcomes were a diagnosis of osteoporosis or MOF. Hazard ratios (HRs) adjusted for age, sex, socioeconomic status, medication use, and comorbidity were calculated with 95% CIs using Cox proportional hazards regression models. RESULTS: A total of 723 251 adults treated with the equivalent of at least 200 g of mometasone were included in the analysis (52.8% women; mean [SD] age, 52.8 [19.2] years). Dose-response associations were found between increased use of potent or very potent TCSs and the risk of osteoporosis and MOF. For example, HRs of MOF were 1.01 (95% CI, 0.99-1.03) for exposure to 500 to 999 g, 1.05 (95% CI, 1.02-1.08) for exposure to 1000 to 1999 g, 1.10 (95% CI, 1.07-1.13) for exposure to 2000 to 9999 g, and 1.27 (95% CI, 1.19-1.35) for exposure to at least 10 000 g. A 3% relative risk increase of osteoporosis and MOF was observed per doubling of the cumulative TCS dose (HR, 1.03 [95% CI, 1.02-1.04] for both). The overall population-attributable risk was 4.3% (95% CI, 2.7%-5.8%) for osteoporosis and 2.7% (95% CI, 1.7%-3.8%) for MOF. The lowest exposure needed for 1 additional patient to be harmed (454 person-years) was observed for MOF with exposure of at least 10 000 g. CONCLUSIONS AND RELEVANCE: These findings demonstrate that use of high cumulative amounts of potent or very potent TCSs was associated with an increased risk of osteoporosis and MOF.

IMPORTANCE: Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced disease severity in moderate to severe atopic dermatitis (AD) in 2 phase 3 monotherapy studies. OBJECTIVE: To assess the efficacy and safety of 4 mg and 2 mg of baricitinib in combination with background topical corticosteroid (TCS) therapy in adults with moderate to severe AD who previously had an inadequate response to TCS therapy. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled, phase 3 randomized clinical trial, BREEZE-AD7 (Study of Baricitinib [LY3009104] in Combination With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis) was conducted from November 16, 2018, to August 22, 2019, at 68 centers across 10 countries in Asia, Australia, Europe, and South America. Patients 18 years or older with moderate to severe AD and an inadequate response to TCSs were included. After completing the study, patients were followed up for up to 4 weeks or enrolled in a long-term extension study. INTERVENTIONS: Patients were randomly assigned (1:1:1) to receive 2 mg of baricitinib once daily (n = 109), 4 mg of baricitinib once daily (n = 111), or placebo (n = 109) for 16 weeks. The use of low-to-moderate potency TCSs was allowed. MAIN OUTCOMES AND MEASURES: The primary end point was the proportion of patients achieving a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 (clear) or 1 (almost clear), with a 2-point or greater improvement from baseline at week 16. RESULTS: Among 329 patients (mean [SD] age, 33.8 [12.4] years; 216 [66%] male), at week 16, a vIGA-AD score of 0 (clear) or 1 (almost clear) was achieved by 34 patients (31%) receiving 4 mg of baricitinib and 26 (24%) receiving 2 mg of baricitinib compared with 16 (15%) receiving placebo (odds ratio vs placebo, 2.8 [95% CI, 1.4-5.6]; P = .004 for the 4-mg group; 1.9 [95% CI, 0.9-3.9]; P = .08 for the 2-mg group). Treatment-emergent adverse events were reported in 64 of 111 patients (58%) in the 4-mg group, 61 of 109 patients (56%) in the 2-mg group, and 41 of 108 patients (38%) in the placebo group. Serious adverse events were reported in 4 patients (4%) in the 4-mg group, 2 (2%) in the 2-mg group, and 4 (4%) in the placebo group. The most common adverse events were nasopharyngitis, upper respiratory tract infections, and folliculitis. CONCLUSIONS AND RELEVANCE: A dose of 4 mg of baricitinib in combination with background TCS therapy significantly improved the signs and symptoms of moderate to severe AD, with a safety profile consistent with previous studies of baricitinib in AD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03733301

IMPORTANCE: Abrocitinib, an oral, once-daily Janus kinase 1 selective inhibitor, was effective and well tolerated in a phase 3 monotherapy trial of patients with moderate-to-severe atopic dermatitis (AD). OBJECTIVE: To investigate the efficacy and safety of abrocitinib in adolescents and adults with moderate-to-severe AD in an identically designed trial. DESIGN, SETTING, AND PARTICIPANTS: This phase 3, double-blinded, placebo-controlled, parallel-group randomized clinical trial included patients 12 years or older with a clinical diagnosis of moderate-to-severe AD for at least 1 year and inadequate response to topical medications given for at least 4 weeks within 6 months. Patients were enrolled from 115 centers in Australia, Bulgaria, Canada, China, Czechia, Germany, Hungary, Japan, South Korea, Latvia, Poland, United Kingdom, and the United States from June 29, 2018, to August 13, 2019. Data were analyzed from September 13 to October 25, 2019. INTERVENTIONS: Patients were randomly assigned (2:2:1) to receive once-daily oral abrocitinib in 200- or 100-mg doses or placebo for 12 weeks. MAIN OUTCOMES AND MEASURES: The coprimary end points were the proportion of patients achieving Investigator Global Assessment (IGA) response (ie, clear [0] or almost clear [1], with improvement of ≥2 grades) and the proportion of patients achieving at least 75% improvement in Eczema Area and Severity Index score (EASI-75) at week 12. Key secondary end points included the proportion of patients achieving a Peak Pruritus Numerical Rating Scale (PP-NRS) response (ie, improvement of ≥4 points) at week 12. Other secondary end points included the proportion of patients achieving at least 90% improvement in EASI score (EASI-90). Safety was assessed via adverse events and laboratory monitoring. RESULTS: A total of 391 patients (229 male [58.6%]; mean [SD] age, 35.1 [15.1] years) were included in the analysis; of these, 155 received abrocitinib, 200 mg/d; 158, abrocitinib, 100 mg/d; and 78, placebo. Among patients with available data at week 12, greater proportions of patients in the 200- and 100-mg abrocitinib groups vs the placebo group achieved IGA (59 of 155 [38.1%] and 44 of 155 [28.4%] vs 7 of 77 [9.1%]; P &lt; .001) and EASI-75 (94 of 154 [61.0%] and 69 of 155 [44.5%] vs 8 of 77 [10.4%]; P &lt; .001), greater estimated proportions achieved PP-NRS (55.3% [95% CI, 47.2%-63.5%] and 45.2% [95% CI, 37.1%-53.3%] vs 11.5% [95% CI, 4.1%-19.0%]; P &lt; .001), and/or greater proportions achieved EASI-90 (58 of 154 [37.7%] and 37 of 155 [23.9%] vs 3 of 77 [3.9%]) responses. Adverse events were reported for 102 patients (65.8%) in the 200-mg group, 99 (62.7%) in the 100-mg group, and 42 (53.8%) in the placebo group; serious adverse events were reported for 2 patients (1.3%) in the 200-mg group, 5 (3.2%) in the 100-mg group, and 1 (1.3%) in the placebo group. Decreases in platelet count (2 [1.3%]) and laboratory values indicating thrombocytopenia (5 [3.2%]) were reported in the 200-mg group. CONCLUSIONS AND RELEVANCE: Monotherapy with once-daily oral abrocitinib was effective and well tolerated in adolescents and adults with moderate-to-severe AD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03575871

Oral Janus kinase inhibitors (JAKis) have black-box warnings of infections, cancer risk, and cardiovascular and venous thromboembolic events. They may be used off-label for chronic hand eczema (CHE).

Allergic contact dermatitis is characterized by its appearance of red, raised and infiltrated, scaling or scabbed skin and intense pruritus, and distinguished from irritant contact dermatitis by its specific immune process and histopathology. Many contact allergens are low-molecular- weight chemicals including metals such as nickel, cobalt, and chromium, preservatives, and adhesives. When such materials are used internally in biomedical devices, they are similarly capable of causing sensitization and an inflammatory response. Sometimes, the reaction remains internal, and presents as swelling, pain, stiffness, decreased range of motion, and internal itching around the implant. Such reactions may, in some cases, also extend to include a localized or, rarely, systemic contact dermatitis indicative of the same process. This review will present an overview of reported skin and local internal reactions to orthopedic implants, which are the largest category of implanted internal metal devices. Immune reactions to smaller categories of medical appliances include cardiac devices and vascular stents, neuromodulation devices, diabetic appliances, Nuss bar surgery for pectus excavatum, and dental and spinal implants. We will review the available diagnostic tools, the consensus on interpretation, and reported strategies for treatment.

Skin barrier function (SBF) disorders are a class of pathologies that affect a significant portion of the world population. These disorders cause skin lesions with intense itch, impacting patients’ physical and psychological well-being as well as their social functioning. It is in the interest of patients that their disorder be monitored closely while under treatment to evaluate the effectiveness of the ongoing therapy and any potential adverse reactions. Symptom-based assessment techniques are widely used by clinicians; however, they carry some limitations. Techniques to assess skin barrier impairment are critical for understanding the nature of the disease and for helping personalize treatment. This review recalls the anatomy of the skin barrier and describes an atomic-force microscopy approach to quantitatively monitor its disorders and their response to treatment. We review a panel of studies that show that this technique is highly relevant for SBF disorder research, and we aim to motivate its adoption into clinical settings.

Biomarkers associated with disease severity and comorbid metabolic syndrome (MetS) in patients with hidradenitis suppurativa (HS) are lacking.

Although previous studies have explored racial/ethnic differences in incident atopic dermatitis (AD) in childhood, few studies have examined risk factors associated with AD persistence. As such, we sought to examine differences in incidence and persistence of childhood AD by race/ethnicity accounting for sociodemographic characteristics and perinatal vitamin D levels. Using data from Project Viva, a prospective prebirth cohort in eastern Massachusetts, we studied 1,437 mother-child pairs with known AD status to examine the associations of race/ethnicity with maternally reported child AD. We used multivariable logistic regression, adjusting for sociodemographic factors and maternal plasma vitamin D, to estimate adjusted odds ratios (aORs) of AD incidence at early childhood and persistence at mid-childhood. Compared to non-Hispanic whites, non-Hispanic blacks (aOR = 2.71, 95% confidence interval = 1.75–4.19) and other non-Hispanics (aOR = 1.80, 95% confidence interval = 1.16–2.80) were more likely to have incident AD. Non-Hispanic blacks (aOR = 6.26, 95% confidence interval = 2.32–16.88) and Hispanics (aOR = 6.42, 95% CI = 1.93–21.41) with early childhood AD were more likely to have persistent AD. In conclusion, compared with non-Hispanic whites, AD incidence and persistence are higher among certain nonwhite racial/ethnic subgroups. Further research is warranted to identify environmental, socioeconomic, and genetic factors that may be responsible for the observed differences.

In psoriasis patients, incidence rates of Crohn disease (CD) and ulcerative colitis (UC) have been increased in epidemiological studies and certain clinical trials, yet the association remains poorly understood. We studied a 20-year nationwide cohort of 235,038 Danish adults with psoriasis and a 1:1 matched reference group. Less than 1% of psoriasis patients developed CD or UC during follow-up. Incidence rates of CD were highest for younger women with psoriasis and patients with concurrent psoriatic arthritis, whereas men with psoriasis had particularly high incidence rates of UC compared with their non-psoriasis peers. Adjusted hazard ratios of CD were 1.84 (95% confidence interval [CI]= 1.47–2.29) and 2.38 (95% CI = 1.62–3.49) among psoriasis patients treated with topical and systemic nonbiologic therapy, respectively. No definite CD cases occurred during biologic therapy. For UC, adjusted hazard ratios were 1.49 (95% CI = 1.29–1.72), 1.51 (95% CI = 1.14–2.01), and 1.23 (95% CI = 0.39–3.86, P = 0.7197) for psoriasis patients receiving topical, systemic nonbiologic, and biologic therapy, respectively. Time to CD (but not UC) diagnosis was significantly longer for psoriasis patients compared with the general population, and patients receiving systemic treatment had the longest time to CD and UC. Psoriasis was associated with increased risk of CD and UC. Particular risk factors included sex and psoriatic arthritis.

IMPORTANCE: Knowledge about factors associated with persistence of atopic dermatitis (AD) during childhood is sparse. OBJECTIVE: To explore heritable, environmental, and clinical factors associated with persistent AD based on 13 years’ follow-up of an at-risk birth cohort. DESIGN, SETTING, AND PARTICIPANTS: In the Copenhagen Prospective Study on Asthma in Childhood 2000 (COPSAC2000) clinical birth cohort study, 411 children born to mothers with asthma were followed up until the age of 13 years at a clinical research unit in Copenhagen, Denmark, from August 1998 to June 2015. Atopic dermatitis was diagnosed prospectively during close clinical follow-up according to the criteria of Hanifin and Rajka. Data were gathered on parental history, social circumstances, and environmental factors through parent interviews. The cohort was followed up with biannual visits to the clinic until the age of 7 years and were seen again at age 13 years. Data were analyzed from August 2015 to January 2018. MAIN OUTCOMES AND MEASURES: Atopic dermatitis was diagnosed using Hanifin and Rajka major and minor criteria, and severity was determined by Scoring Atopic Dermatitis (SCORAD) index, with possible scores from 0 to 83, with higher scores indicating more severe AD. RESULTS: Of the 411 children in the cohort, 203 (49.4%) were male and 186 (45.3%) were diagnosed with AD before the age of 13 years; 40 of 166 children (24.1%) had persistent AD at the age of 13 years, and 126 (76.0%) experienced remission. Factors associated with persistent AD to age 13 years included heritability, environmental exposures, asthma and allergic sensitization, clinical presentation at the time of diagnosis, the composition of Hanifin and Rajka diagnostic minor criteria, and AD severity according to SCORAD. A higher AD genetic risk score was associated with an increased the risk for persistent AD (multivariable odds ratio [OR], 1.8; 95% CI, 1.1-2.9; P = .02), together with paternal asthma (multivariable OR, 3.7; 95% CI, 1.2-11.5; P = .02); paternal AD (multivariable OR, 6.2; 95% CI, 1.17-23.2; P = .007), and higher social circumstances (multivariable OR, 1.6; 95% CI, 1.0-2.5; P = .05). Particular clinical presentations at time of diagnosis were also associated with specific minor criteria of Hanifin and Rajka (Dennie-Morgan and anterior neck folds, white dermographism, intolerance to wool, itching when sweating, tendency to skin infection, food intolerance, and food allergy) (OR, 2.6; 95% CI, 1.1-6.2; P = .03) as well as increased severity at diagnosis (OR, 1.1; 95% CI, 1.0-1.1; P = .007). CONCLUSIONS AND RELEVANCE: In a birth cohort of children at risk for asthma who received close clinical follow-up to age 13 years, known genetic AD risk variants, paternal asthma and AD, high social circumstances, diagnostic minor criteria, and disease severity at onset were associated with persistent AD at age 13 years. These findings may be applied in clinical practice to evaluate the likely disease course for individual patients.

It is currently unknown whether alterations in the skin microbiome exist before development of atopic dermatitis (AD). In this prospective Danish birth cohort of 300 children, we examined whether skin microbiome alterations during the first 2 months of life were associated with an increased risk of AD in the first 2 years and its severity after adjustment for environmental factors and selected skin chemokine and natural moisturizing factor levels. We found no overall association between the skin microbiome at birth and age 2 months and AD during the first 2 years of life. However, when restricting the analysis to children with at least one parent with atopy, a lower alpha diversity at age 2 months was associated with an increased risk of AD (adjusted hazard ratio = 1.7, 95% confidence interval = 1.1–2.6). We observed a stronger association in children where both parents had atopy (adjusted hazard ratio = 4.4, 95% confidence interval = 1.1–18.2). The putative pathogenic role of changes in the skin microbiome on AD risk remains uncertain but may play a role in those with an atopic predisposition.

Hand eczema (HE) is a prevalent skin disease. However, the classification of HE into different subtypes remains challenging. A limited number of previous studies have employed invasive biopsy–based strategies; yet, studies of the HE proteome using noninvasive tape-stripping methodology have not been reported. In this study, we wanted to assess whether global proteomic analysis of skin tape strip samples can be used for subclassification of patients with HE. Tape strips were collected from patients with HE and healthy skin. Liquid chromatography–mass spectrometry proteomics was performed, and the global protein expression was analyzed. We identified 2,919 proteins in stratum corneum–derived skin cells from tape strip samples. Compared with healthy skin, the lesional samples from patients with HE exhibited increased expression of immune-related markers and a decreased expression of structural barrier proteins. The difference between HE subtypes was restricted to the lesional skin areas and included an increased expression of skin barrier–related proteins independently of the concurrent AD. In conclusion, we found that the noninvasive tape strip method used in combination with liquid chromatography–mass spectrometry proteomics can be used for analysis of skin protein expression in patients with HE. Thus, the method shows potential for assessing the proteomic differences between subtypes of HE and biomarker discovery.

This article provides an overview of clinical aspects of hand eczema in patients with atopic dermatitis. Hand eczema can be a part of atopic dermatitis itself or a comorbidity, for example, as irritant or allergic contact dermatitis. When managing hand eczema, it is important to first categorize the subtype and identify potential culprit allergens or irritants. First-line therapy should be a combination of emollients and topical corticosteroids; possible alternatives include topical calcineurin inhibitors or coal tar. Second-line therapy includes UV therapy and systemic therapy, including azathioprine, cyclosporine, methotrexate, and mycophenolate. Prednisolone should only be very infrequently used.

Little is known about the inpatient burden of atopic dermatitis (AD). We sought to determine the risk factors and financial burden of hospitalizations for AD in the United States. Data were analyzed from the 2002–2012 National Inpatient Sample, including a 20% representative sample of all hospitalizations in the United States. Hospitalization rates for AD or eczema were highest in the northeast during the winter and south during the summer. Geometric mean cost of care (95% confidence interval) was lower for a primary diagnosis of AD or eczema versus no AD or eczema in adults ($3,502 [$3,360–$3,651] vs. $6,849 [$6,775–$6,925]; P = 0.0004) and children ($2,716 [$2,542–$2,903] vs. $4,488 [$4,302–$4,682]; P = 0.0004). However, the high prevalence of hospitalization resulted in total inpatient costs of $8,288,083 per year for adults and $3,333,868 per year for children. In conclusion, there is a substantial inpatient financial burden of AD in the United States.

Psoriasis is a chronic inflammatory skin disease affecting approximately 3% of the general population. Over the past decades, psoriasis has been associated with a range of comorbidities. In the current review, we summarize epidemiological and pathophysiological traits of comorbidities in patients with psoriasis. In addition to psoriatic arthritis, studies have found increased prevalence of certain cancers, as well as cardiometabolic, neuropsychiatric, gastroenterologic and autoimmune diseases in patients with psoriasis. While the etiopathogenesis is likely multifactorial, psoriasis-associated systemic low-grade inflammation is believed to play an important role in the development and maintenance of a number of these concurring diseases. In order to effectively manage patients with psoriasis, increased awareness and timely intervention on such comorbidities and modifiable risk factors are warranted by treating physicians. Since comorbidities may confer a substantial disease and healthcare burden, the importance of routine screening for high-prevalence and high-risk comorbidities in patients with psoriasis should be emphasized.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. In small studies, inflammatory bowel disease has been associated with the increased prevalence of HS, but the data on the concurrence of inflammatory bowel disease in patients with HS are limited. We therefore investigated the prevalence and risk of inflammatory bowel disease in patients with HS compared with the general population. The study linked all Danish individuals aged ≥18 years in nationwide registers. Adjusted odds ratios and adjusted hazard ratios were estimated by logistic regression and Cox regression, respectively. The study comprised 7,732 patients with HS and 4,354,137 subjects from the general population. The prevalence (HS vs. general population) was 0.8% and 0.3% (odds ratio 2.04; 1.59–2.62) for Crohn’s disease and 1.3% and 0.7% (odds ratio 1.75; 1.44–2.13) for ulcerative colitis. The risk of new-onset Crohn’s disease (hazard ratio 2.19; 1.44–3.34) and ulcerative colitis (hazard ratio 1.63; 1.18–2.27) was significantly increased among patients with HS. In conclusion, HS was significantly associated with the presence and risk of new-onset inflammatory bowel disease, although the prevalence remained low. Gastrointestinal complaints in patients with HS should warrant further clinical examination.

In this review article, we summarize the current evidence about atopic dermatitis (AD)-associated comorbidities, beyond the traditional atopic and allergic conditions. Patients with AD may have an increased risk of cardiovascular diseases, certain malignancies, autoimmune diseases, and neuropsychiatric diseases. The causes of these associations are likely multifactorial and may include genetic predispositions, systemic low-grade inflammation, environmental exposures, medication, and lifestyle and behavioral risk factors. There appears to be geographical variations in prevalence of comorbidities in patients with AD, indicating that differences in ethnicity and lifestyle factors may significantly influence the risk of certain comorbidities. The reported comorbidities in recent literature emphasize the burden of disease in patients with AD. Early appropriate AD therapy, in combination with reduction of risk factors, may help prevention of certain comorbidities. The reported observations may generate hypotheses for future investigations in underlying risk factors for AD-associated comorbidities.

Die Haut ist eine wichtige Barriere, die den Organismus vor mechanischer Belastung, Mikroorganismen, Chemikalien und Allergenen schützt, umgekehrt aber auch die wichtige Funktion erfüllt, den Flüssigkeitsverlust zu reduzieren. Ein gemeinsames Kennzeichen vieler Dermatosen ist eine beeinträchtigte Funktionsfähigkeit der Hautbarriere, und man könnte vermuten, dass hier durch vermehrtes Eindringen potenzieller Allergene ein erhöhtes Risiko für Kontaktsensibilisierung (CS) und Allergie besteht. Die Beziehung zwischen häufigen Hauterkrankungen wie Psoriasis, atopischer Dermatitis (AD) und irritativer Kontaktdermatitis (ICD) einerseits und der Entwicklung einer Kontaktallergie (CA) andererseits ist jedoch komplex und hängt außer vom Zustand der Hautbarriere auch von verschiedenen immunologischen Reaktionen ab. Psoriasis ist in der Vergangenheit immer als Th1-dominierte Krankheit betrachtet worden, doch die Entdeckung von Th17-Zellen und IL-17 hat neue und interessante Informationen bezüglich der Pathogenese beigesteuert. Die wissenschaftliche Evidenzlage deutet auf eine inverse Beziehung zwischen Psoriasis und CA hin, die möglicherweise durch eine erhöhte Konzentration an Th17-Zellen und den dazugehörigen Zytokinen bedingt ist. Was die AD angeht, so ist eine positive Assoziation mit CS in epidemiologischen Studien etabliert worden, allerdings liegt hierfür noch keine Erklärung vor. Experimentelle Studien zeigen jedoch eine inverse Beziehung zwischen AD und CS. Die gegensätzlichen und wechselseitig antagonistischen Einflüsse von Th1- (CS) und Th2-Zellen (AD) sind als mögliche Erklärung hierfür angeführt worden. Schließlich liegen überzeugende Belege dafür vor, dass die Exposition gegenüber Reizstoffen das CS-Risiko erhöht und Patienten mit ICD somit einem erhöhten Risiko für CA unterliegen. Hautreizungen führen zur Freisetzung von IL-1 und TNF-α, was sich wiederum auf die Aktivität antigenpräsentierender Zellen auswirkt, ihre Migration zu lokalen Lymphknoten fördert und so die Wahrscheinlichkeit für eine CS und letztlich die Entwicklung einer CA erhöht. Übersetzung aus Curr Probl Dermatol. Basel, Karger, 2016, vol 49, pp 90-102 (DOI:10.1159/000441548)

The real-world efficacy of biologics may be insufficiently assessed through common drug survival studies. The objective was thus to examine the real-world performance of biologics in the treatment of psoriasis using the composite endpoint of either discontinuation or off-label dose escalation. Using a prospective nationwide registry (DERMBIO, 2007–2019), we included patients with psoriasis treated with adalimumab, secukinumab, and/or ustekinumab, which have all been used as first-line therapy during the inclusion period. The primary endpoint was a composite of either off-label dose escalation or discontinuation of treatment, whereas the secondary outcomes were dose escalation and discontinuation, respectively. Kaplan-Meier curves were used for the presentation of unadjusted drug survival curves. Cox-regression models were used for risk assessment. In 4,313 treatment series (38.8% women, mean age 46.0 years, and 58.3% bio-naivety), we found that the risk of the composite endpoint was lower for secukinumab when compared with ustekinumab (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.59–0.76), but higher for adalimumab (HR 1.15, 95% CI 1.05–1.26). However, the risk of discontinuation was higher for secukinumab (HR 1.24, 95% CI 1.08–1.42) and adalimumab (HR 2.01, 95% CI 1.82–2.22). For bio-naive patients treated with secukinumab, the risk of discontinuation was comparable to that of ustekinumab (HR 0.95, 95% CI 0.61–1.49).

Contact dermatitis because of use of diabetes devices is frequent in individuals with type 1 diabetes, especially in the pediatric age group, but the putative role of a constitutional impaired skin barrier in persons with type 1 diabetes is unclear. This study examined the skin barrier function by measurement of natural moisturizing factor and free cytokines collected via skin tape strips, as well as biophysical markers and the skin microbiome, in persons with type 1 diabetes compared to age- and sex-matched healthy controls. All measurements were done in non-lesional skin. We found that skin barrier function was similar in children and adolescents with type 1 diabetes compared to controls but found that the beta diversity of skin microbiome at the buttock differed between the two groups. We conclude that individuals with type 1 diabetes have normal skin barrier function, and that the increased occurrence of contact dermatitis following pump and sensor use is explained by exogenous factors.

Allergic contact dermatitis (ACD) may complicate the clinical course of atopic dermatitis (AD), and patch testing remains the criterion standard for diagnosing ACD. To date, there have been no guidelines or consensus recommendations on when and how to patch test individuals with AD. Failure to patch test when appropriate may result in overlooking an important and potentially curable complicating comorbidity. In this article, we present consensus recommendations regarding when to perform patch testing in the AD patient, best practices, and common pitfalls. Patch testing should be considered in AD patients with dermatitis that fails to improve with topical therapy; with atypical/changing distribution of dermatitis, or pattern suggestive of ACD; with therapy-resistant hand eczema in the working population; with adult- or adolescent-onset AD; and/or before initiating systemic immunosuppressants for the treatment of dermatitis. A suggested patch testing algorithm for AD patients is provided.

IMPORTANCE: The pathogenesis of rosacea is unclear, but increased matrix metalloproteinase target tissue activity appears to play an important role. Parkinson disease and other neurodegenerative disorders also display increased matrix metalloproteinase activity that contribute to neuronal loss. OBJECTIVE: To investigate the risk of incident (new-onset) Parkinson disease in patients with rosacea. DESIGN, SETTING, AND PARTICIPANTS: A nationwide cohort study of the Danish population was conducted using individual-level linkage of administrative registers. All Danish citizens 18 years or older from January 1, 1997, to December 31, 2011 (N = 5 472 745), were included. Data analysis was conducted from June 26 to July 27, 2015. MAIN OUTCOMES AND MEASURES: The main outcome was a diagnosis of Parkinson disease. Incidence rates (IRs) per 10 000 person-years were calculated, and incidence rate ratios (IRRs) adjusted for age, sex, socioeconomic status, smoking, alcohol abuse, medication, and comorbidity were estimated by Poisson regression models. RESULTS: A total of 5 404 692 individuals were included in the reference population; of these, 22 387 individuals (9812 [43.8%] women; mean [SD] age at diagnosis, 75.9 [10.2] years) received a diagnosis of Parkinson disease during the study period and 68 053 individuals (45 712 [67.2%] women; mean age, 42.2 [16.5] years) were registered as having rosacea. The IRs of Parkinson disease per 10 000 person-years were 3.54 (95% CI, 3.49-3.59) in the reference population and 7.62 (95% CI, 6.78-8.57) in patients with rosacea. The adjusted IRR of Parkinson disease was 1.71 (95%, CI 1.52-1.92) in patients with rosacea compared with the reference population. There was a 2-fold increased risk of Parkinson disease in patients classified as having ocular rosacea (adjusted IRR, 2.03 [95% CI, 1.67-2.48]), and tetracycline therapy appeared to reduce the risk of Parkinson disease (adjusted IRR, 0.98 [95% CI, 0.97-0.99]). CONCLUSIONS AND RELEVANCE: Rosacea constitutes an independent risk factor for Parkinson disease. This association could be due to shared pathogenic mechanisms involving elevated matrix metalloproteinase activity. The clinical consequences of this association require further study.

IMPORTANCE: Rosacea, a common facial skin disorder, has a poorly understood pathogenesis in which increased matrix metalloproteinase activity might play an important role. Glioma accounts for 80% of all primary malignant tumors in the central nervous system, and these tumors also show upregulation of certain matrix metalloproteinases. OBJECTIVE: To investigate the association between rosacea and the risk for glioma. DESIGN, SETTING, AND PARTICIPANTS: Nationwide cohort study of the Danish population from individual-level linkage of administrative registers. All Danish citizens 18 years or older from January 1, 1997, to December 31, 2011, were eligible for inclusion. A total of 5 484 910 individuals were eligible for analysis; of these, 68 372 had rosacea and 5 416 538 constituted the reference population. Data were analyzed from July 14 to August 10, 2015. MAIN OUTCOMES AND MEASURES: The outcome of interest was a diagnosis of glioma. Incidence rates per 10 000 person-years were calculated, and incidence rate ratios adjusted for age, sex, and socioeconomic status were estimated by Poisson regression distribution models. RESULTS: Of the 5 484 910 individuals in the study population, 21 118 individuals developed glioma during the study period, including 20 934 of the 5 416 538 individuals in the reference population (50.4% women; mean [SD] age, 40.8 [19.7] years) and 184 of the 68 372 patients with rosacea (67.3% women; mean [SD] age, 42.2 [16.5] years). The incidence rate (95% CI) of glioma was 3.34 (3.30-3.39) in the reference population and 4.99 (4.32-5.76) in patients with rosacea. The adjusted incidence rate ratio (95% CI) of glioma in patients with rosacea was 1.36 (1.18-1.58) in our primary analysis. When analyses were limited to patients with a primary diagnosis of rosacea by a hospital dermatologist (n = 5964), the adjusted incidence rate ratio was 1.82 (1.16-2.86). CONCLUSIONS AND RELEVANCE: Rosacea was associated with a significantly increased risk for glioma in a nationwide cohort. This association may be mediated, in part, by mechanisms dependent on matrix metalloproteinases. Increased focus on neurologic symptoms in patients with rosacea may be warranted.

Les patients atteints de dermatite atopique (DA) présentent un prurit, une douleur cutanée et des troubles du sommeil, symptômes qui contribuent au stress psychologique (anxiété et dépression). L’abrocitinib est un inhibiteur sélectif de la Janus kinase 1 à prendre par voie orale une fois par jour qui s’est montré efficace et sûr pour traiter la DA modérée à sévère dans un essai de phase IIb et les phases III (JADE MONO-1 et JADE MONO-2 en monothérapie). L’abrocitinib a amélioré les symptômes de la DA dans ces études, mais son impact sur le stress psychologique n’a pas été analysé en détail.