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BackgroundWide-ranging psoriasis prevalence estimates have been reported, possibly due to methodological differences.ObjectivesTo assess the prevalence of psoriasis in Denmark and to validate the use of questionnaire-based data to identify patients with psoriasis.MethodsWe used data from the Danish Skin Cohort, a prospective cohort comprising general population adults, as well as patients with dermatologist-verified psoriasis and atopic dermatitis, respectively. The general population cohort was interviewed to assess the psoriasis prevalence in Denmark, and validation of the questions was performed.ResultsFrom 3490 general population participants, 7.9% (n=275) were found to have self-reported psoriasis. Of these, 221 (prevalence 6.3%) had their disease diagnosed by a physician (the dermatologist-diagnosed prevalence was 4.3%), whereas 54 (prevalence 1.6%) were not diagnosed by a physician. A total of 176 (5%) had active psoriasis within the last 12 months. More than half of patients had at least one disease flare in the last 12 months, and 44.4% of patients with psoriasis had at least one family member with psoriasis, whereas this was only the case for 13.7% of non-psoriasis individuals. Validation of the psoriasis diagnosis yielded a high sensitivity and specificity, with little incremental value of limiting diagnoses to those diagnosed by a physician.ConclusionThe lifetime-prevalence of self-reported psoriasis was found to be 7.9%, whereas the 1-year prevalence (ie, currently active psoriasis) was 5.0%. If used appropriately, questionnaire-based data may accurately identify patients with psoriasis.

Filaggrin null mutations result in impaired skin barrier functions, increase the risk of early onset atopic dermatitis and lead to a more severe and chronic disease. We aimed to characterize the clinical presentation and course of atopic dermatitis associated with filaggrin mutations within the first 7 years of life. The COPSAC cohort is a prospective, clinical birth cohort study of 411 children born to mothers with a history of asthma followed during their first 7 years of life with scheduled visits every 6 months, as well as visits for acute exacerbations of dermatitis. Atopic dermatitis was defined in accordance with international guidelines and described at every visit using 35 predefined localizations and 10 different characteristics. A total of 170 (43%) of 397 Caucasian children developed atopic dermatitis. The R501X and/or 2282del4 filaggrin null mutations were present in 26 (15%) of children with atopic dermatitis and were primarily associated with predilection to exposed skin areas (especially the cheeks and back of the hands) and an up-regulation of both acute and chronic dermatitis. Furthermore, we found the filaggrin mutations to be associated with a higher number of unscheduled visits (3.6 vs. 2.7; p=0.04) and more severe (moderate-severe SCORAD 44% vs. 31%; p=0.14), and widespread dermatitis (10% vs. 6% of the body area, p<0.001) with an earlier age at onset (246 vs. 473 days, p<0.0001) compared to wild-type. In children, filaggrin mutations seem to define a specific endotype of atopic dermatitis primarily characterized by predilection to exposed areas of the body, in particular hands and cheeks, and an up-regulation in both acute and chronic morphological markers. Secondary, this endotype is characterized by an early onset of dermatitis and a more severe course, with more generalized dermatitis resulting in more frequent medical consultations.

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.

Background The Itch Numeric Rating Scale (NRS), Skin Pain NRS, and Atopic Dermatitis Sleep Scale (ADSS) are self-administered patient-reported outcome (PRO) instruments developed to assess symptoms in patients with atopic dermatitis (AD). The objective of this study was to evaluate the psychometric properties (reliability, validity, and responsiveness) and interpretability thresholds of these PROs using data from three pivotal Phase 3 studies in adults. Methods BREEZE-AD1, BREEZE-AD2, and BREEZE-AD5 evaluated the safety and efficacy of baricitinib in adults with moderate-to-severe AD. Clinician-reported outcomes and other PROs commonly assessed in patients with AD were used to estimate meaningful changes and evaluate test–retest reliability, convergent and divergent validity, known-groups validity, responsiveness, and meaningful change thresholds (MCTs) of the Itch NRS, Skin Pain NRS, and ADSS. Results The test–retest reliability of the Itch NRS, Skin Pain NRS, and ADSS was evidenced by generally large intraclass correlation coefficients (> 0.7) in stable groups of patients between baseline and Week 1 and Weeks 4 and 8. Moderate-to-large correlations ( r  > 0.4) at baseline and Week 16 were generally observed between each measure and other PROs measuring the same concept, supporting convergent validity. Small-to-moderate correlations with clinician-reported outcomes demonstrated divergent validity. Each instrument was able to distinguish between known groups of disease severity as assessed using other indicators of AD severity. The responsiveness of the Itch NRS, Skin Pain NRS, and ADSS scales was demonstrated through significant differences in their change scores from baseline to Week 16 between categories of change in another PRO also from baseline to Week 16. Thresholds for interpreting meaningful change were estimated as − 4.0 for the 0–10 Itch and Skin Pain NRS items; − 1.25 for the 0–4 ADSS Items 1 and 3 and; − 1.50 for the 0–29 ADSS Item 2, these equivalent to moderate degrees of change. Conclusions Results of this study demonstrate that the psychometric properties of the Itch NRS, Skin Pain NRS, and ADSS are good to excellent. These findings support the use of these instruments in daily assessment of AD symptoms in adults with moderate-to-severe AD. Trial registration ClinicalTrials.gov numbers: NCT03334396, NCT03334422, and NCT03435081.

Extracellular matrix (ECM) remodeling of the skin is a continuous process necessary for maintaining tissue homeostasis. Type VI collagen (COL6) is characterized as a beaded filament, located in the dermal ECM, where COL6-α6-chain has been demonstrated upregulated in atopic dermatitis. The aim of this study was to develop and validate a competitive ELISA, targeting the N-terminal of COL6-α6-chain, named C6A6, and evaluate its associations with the dermatological condition’s atopic dermatitis, psoriasis, hidradenitis suppurativa, systemic lupus erythematosus, systemic sclerosis, urticaria, vitiligo, and cutaneous malignant melanoma in comparison, to healthy controls. A monoclonal antibody was raised and employed in an ELISA assay. The assay was developed, technically validated, and evaluated in two independent patient cohorts. Cohort 1 showed C6A6 was significantly elevated in patients with atopic dermatitis ( p  < 0.0001), psoriasis ( p  < 0.0001), hidradenitis suppurativa ( p  = 0.0095), systemic lupus erythematosus ( p  = 0.0032) and melanoma ( p  < 0.0001) compared to healthy donors. Cohort 2 confirmed C6A6 being upregulated in atopic dermatitis compared to healthy controls ( p  < 0.0001), but also associated with disease severity (SCORAD, p  = 0.046) and lowered in patients receiving calcineurin inhibitors ( p  = 0.014). These findings are hypothesis generating, and the utility of the C6A6 biomarker for disease severity and treatment response needs to be validated in larger cohorts and longitudinal studies.

Background To estimate the prevalence of ocular surface disorders (OSDs) by atopic dermatitis (AD) status and evaluate healthcare resource utilization (HRU) among patients with AD. Methods Patients (all ages) enrolled in the Optum Clinformatics ® database were included in this two-part, retrospective, observational, cross-sectional study using administrative claims data. For objective 1, patients with/without AD who had continuous enrollment from July 1, 2018, through December 31, 2019, were included; for objective 2, patients with AD who had ≥ 18 months of continuous enrollment any time during April 1, 2016, through December 31, 2018. OSD prevalence was compared between patients with an AD diagnosis vs. those without. HRU was assessed among patients with AD and continuous enrollment for 6 months before and 12 months after AD diagnosis. Results A total of 79,761 patients with AD and 11,313,523 without AD were included in objective 1. By AD status, OSD prevalence was higher among patients with vs. those without AD (16.9% vs. 9.5%); by age, it was highest among children aged ≤ 5 years (11.4%). The most common OSD was conjunctivitis (8.7% vs. 3.1% by AD status). Among 325,979 patients with AD in objective 2, there was a mean ± standard deviation of 0.87 ± 3.44 OSD-related claims during a 1-year period. Among those with a ≥ 1 OSD-related claim, the mean number of claims was 4.46 ± 7.05. Patients with vs. those without an OSD during the 6 months before their AD diagnosis had higher all-cause HRU during the following year, mainly pharmacy claims (30.5 ± 41.45 vs. 21.23 ± 32.66) and outpatient visits (32.41 ± 34.50 vs. 21.36 ± 28.59). Conclusions In this US claims database study, the proportion of patients with ≥ 1 OSD-related claim was 1.8 times higher among patients with vs. without AD, with considerable OSD-related HRU. The highest rates of OSD were seen in children aged ≤ 5 years.

About 20% of the general population is contact-sensitized to common haptens such as fragrances, preservatives, and metals. Many also develop allergic contact dermatitis (ACD), the clinical manifestation of contact sensitization. ACD represents a common health issue and is also one of the most important occupational diseases. Although this inflammatory skin disease is mediated predominantly by memory T lymphocytes recognizing low-molecular-weight chemicals after skin contact, the innate immune system also plays an important role. Along that line, the presence of irritants may increase the risk of ACD and therefore ACD is often seen in the context of irritant contact dermatitis. In this review article, we discuss recent progress in basic research that has dramatically increased our understanding of the pathomechanisms of ACD and provides a basis for the development of novel diagnostic and therapeutic measures. Current methods for diagnosis as well as treatment options of ACD are also discussed.

Introduction The comparative efficacy of targeted systemic therapies for moderate to severe atopic dermatitis (AD) has not been systematically assessed using recent phase 3 data. This network meta-analysis assesses the comparative efficacy of targeted systemic therapies without the addition of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) in adults with moderate to severe AD. Methods The systematic literature review searched through 17 May 2021 for phase 3/4 trials with upadacitinib, interleukin-4 (IL-4), interleukin-13 (IL-13), or JAK inhibitors compared with placebo or active intervention for adults and adolescents with moderate to severe AD with inadequate response to TCS/TCI or for whom TCS/TCI was medically inadvisable, without restrictions on year or region. Researchers assessed data using PRISMA guidelines. The proportion of patients achieving trial co-primary endpoints [Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and reduction of ≥ 2 points from baseline; proportion of patients achieving Eczema Area and Severity Index (EASI) improvement ≥ 75% from baseline (EASI-75)]; EASI improvement ≥ 90% from baseline (EASI-90); and ≥ 4-point improvement on Pruritus Numerical Rating Scale from baseline (ΔNRS ≥ 4) were evaluated using Bayesian network meta-analysis. Results Of 3415 initially identified records, network meta-analysis (NMA) ultimately included 6 records representing 9 unique studies. Two upadacitinib trials were also included. Eleven clinical trials including 6254 patients were analyzed. Upadacitinib 30 mg daily was the most efficacious therapy across all endpoints at the primary endpoint (week 12 or 16) and at earlier timepoints, followed by upadacitinib 15 mg daily and abrocitinib 200 mg daily. Discussion Many factors need to be considered for treatment selection for AD. These findings can help healthcare providers when personalizing a patient’s treatment. Conclusion Upadacitinib 30 mg daily, upadacitinib 15 mg daily, and abrocitinib 200 mg daily may be the most efficacious targeted systemic therapies over 12–16 weeks of therapy in AD.

We present 2 cases of rosacea that were successfully managed with off-label treatment. The first is a case of painful, exuding papulopustular lesions of the nose treated with rifaximin, and the other is a case of severe, debilitating and painful flushing treated with sumatriptan. The cases support previous notions that gastrointestinal comorbidities may be related to papulopustular lesions and that flushing may be related to neurogenic inflammation and migraine. The cases also imply that a new approach to rosacea management, based on endotypes and comorbidities, may be warranted.

Abrocitinib, an oral selective Janus kinase 1 inhibitor, was effective and well tolerated in adults with moderate-to-severe atopic dermatitis in a phase 2b trial. We aimed to assess the efficacy and safety of abrocitinib monotherapy in adolescents and adults with moderate-to-severe atopic dermatitis. In this multicentre, double-blind, randomised phase 3 trial (JADE MONO-1), patients (aged ≥12 years) with moderate-to-severe atopic dermatitis (Investigator Global Assessment score ≥3, Eczema Area and Severity Index [EASI] score ≥16, percentage of body surface area affected ≥10%, and Peak Pruritus Numerical Rating Scale score ≥4) with a bodyweight of 40 kg or more, were enrolled at 69 sites in Australia, Canada, Europe, and the USA. Patients were randomly assigned (2:2:1) to oral abrocitinib 100 mg, abrocitinib 200 mg, or placebo once daily for 12 weeks. Randomisation was done using an interactive response technology system, stratified by baseline disease severity and age. Patients, investigators, and the funder of the study were masked to study treatment. The coprimary endpoints were the proportion of patients who had achieved an Investigator Global Assessment response (score of 0 [clear] or 1 [almost clear] with a ≥2-grade improvement from baseline), and the proportion of patients who achieved at least a 75% improvement in EASI score from baseline (EASI-75) score, both assessed at week 12. Efficacy was assessed in the full analysis set, which included all randomised patients who received at least one dose of study medication. Safety was assessed in all randomised patients. This study is registered with ClinicalTrials.gov, NCT03349060. Between Dec 7, 2017, and March 26, 2019, 387 patients were enrolled: 156 were assigned to abrocitinib 100 mg, 154 to abrocitinib 200 mg, and 77 to placebo. All enrolled patients received at least one dose of study treatment and thus were evaluable for 12-week efficacy. Of the patients with available data for the coprimary endpoints at week 12, the proportion of patients who had achieved an Investigator Global Assessment response was significantly higher in the abrocitinib 100 mg group than in the placebo group (37 [24%] of 156 patients vs six [8%] of 76 patients; p=0·0037) and in the abrocitinib 200 mg group compared with the placebo group (67 [44%] of 153 patients vs six [8%] of 76 patients; p<0·0001). Of the patients with available data for the coprimary endpoints at week 12, compared with the placebo group, the proportion of patients who had achieved an EASI-75 response was significantly higher in the abrocitinib 100 mg group (62 [40%] of 156 patients vs nine [12%] of 76 patients; p<0·0001) and abrocitinib 200 mg group (96 [63%] of 153 patients vs nine [12%] of 76 patients; p<0·0001). Adverse events were reported in 108 (69%) of 156 patients in the abrocitinib 100 mg group, 120 (78%) of 154 patients in the abrocitinib 200 mg group, and 44 (57%) of 77 patients in the placebo group. Serious adverse events were reported in five (3%) of 156 patients in the abrocitinib 100 mg group, five (3%) of 154 patients in the abrocitinib 200 mg group, and three (4%) of 77 patients in the placebo group. No treatment-related deaths were reported. Monotherapy with oral abrocitinib once daily was effective and well tolerated in adolescents and adults with moderate-to-severe atopic dermatitis. Pfizer.