Laura Maintz

Background: There are conflicting data on a potential association between atopic dermatitis (AD) and cardiovascular diseases (CVD). The aim of this study was to further explore this connection and whether there are biomarkers indicating the risk for CVD in AD patients. Methods: We included 677 AD patients and 79 nonatopic controls from an observational multicenter case–control study (ProRaD: Prospective longitudinal study investigating the remission phase in patients with atopic dermatitis and other allergy‐associated diseases). AD severity and atopic, metabolic, and cardiovascular conditions as well as risk factors were assessed. Serum samples were analyzed with targeted proteomics (cardiometabolics panel, Olink). Results: We did not find an overall association between AD and CVD. However, AD patients without atopic comorbidities (pure AD) showed a significantly higher CVD prevalence than AD patients with atopic comorbidities (ADAC) (28.2% [37/131] vs. 14.7% [80/546], p < 0.001). Yet, this association could not be confirmed when controlling for cardiovascular risk factors. In pure AD, patients with CVD showed a more severe AD than those without CVD (median EASI [Eczema Area and Severity Index] 12.9 vs. 4.0, p < 0.001). In this subgroup of patients, EASI remained a significant predictor of CVD even in the adjusted model (adjusted odds ratio [aOR] = 1.05, p = 0.040). Forty serum cardiometabolic proteins were upregulated in AD patients compared with nonatopic controls. CC‐chemokine ligand 18 (CCL18) was upregulated in both AD ( p < 0.001) and CVD ( p < 0.001) and its increase correlated with AD severity. Conclusions: Our study does not suggest an overall association between AD and CVD, but a more complex relation between the two conditions. Disease severity may be a risk factor for CVD in pure AD patients, but not in those with atopic comorbidities. CCL18 may be a biomarker for CVD.

The 4th Davos Declaration was developed during the Global Allergy Forum in Davos which aimed to elevate the care of patients with atopic dermatitis (AD) by uniting experts and stakeholders. The forum addressed the high prevalence of AD, with a strategic focus on advancing research, treatment, and management to meet the evolving challenges in the field. This multidisciplinary forum brought together top leaders from research, clinical practice, policy, and patient advocacy to discuss the critical aspects of AD, including neuroimmunology, environmental factors, comorbidities, and breakthroughs in prevention, diagnosis, and treatment. The discussions were geared towards fostering a collaborative approach to integrate these advancements into practical, patient‐centric care. The forum underlined the mounting burden of AD, attributing it to significant environmental and lifestyle changes. It acknowledged the progress in understanding AD and in developing targeted therapies but recognized a gap in translating these innovations into clinical practice. Emphasis was placed on the need for enhanced awareness, education, and stakeholder engagement to address this gap effectively and to consider environmental and lifestyle factors in a comprehensive disease management strategy. The 4th Davos Declaration marks a significant milestone in the journey to improve care for people with AD. By promoting a holistic approach that combines research, education, and clinical application, the Forum sets a roadmap for stakeholders to collaborate to improve patient outcomes in AD, reflecting a commitment to adapt and respond to the dynamic challenges of AD in a changing world.

Aim: The 4th Davos Declaration, convened during the Global Allergy Forum (GAF) in Davos, aimed to elevate patient care for patients with atopic dermatitis (AD) by uniting experts and stakeholders. The forum addressed the high prevalence of AD, with a strategic focus on advancing research, treatment, and management to meet the evolving challenges in the field. Methods: This multidisciplinary forum brought together top leaders from research, clinical practice, policy, and patient advocacy to discuss the critical aspects of AD, including neuroimmunology, environmental factors, comorbidities, and breakthroughs in prevention, diagnosis, and treatment. The discussions were geared towards fostering a collaborative approach to integrate these advancements into practical, patient-centric care. Results The forum underlined the mounting burden of AD, attributing it to significant environmental and lifestyle changes. It acknowledged the progress in understanding AD and in developing targeted therapies but recognized a gap in translating these innovations into clinical practice. Emphasis was placed on the need for enhanced awareness, education, and stakeholder engagement to address this gap effectively and to consider environmental and lifestyle factors in a comprehensive disease management strategy. Conclusion: The 4th Davos Declaration marks a significant milestone in the journey to improve care for people with AD. By promoting a holistic approach that combines research, education, and clinical application, the Forum sets a roadmap for stakeholders to work together to improve patient outcomes in AD, reflecting a commitment to adapt and respond to the dynamic challenges of AD in a changing world.

Atopic dermatitis (AD) represents the most common skin disease characterized by heterogeneous endophenotypes and a high disease burden. In Europe, six new systemic therapies for AD have been approved: the biologics dupilumab (anti‐interleukin‐4 receptor (IL‐4R) α in 2017), tralokinumab (anti‐IL‐13 in 2021), lebrikizumab (anti‐IL‐13 in 2023), and the oral janus kinase (JAK) inhibitors (JAKi) targeting JAK1/2 (baricitinib in 2020 in the EU) or JAK1 (upadacitinib in 2021 and abrocitinib in 2022). Herein, we give an update on new approvals, long‐term safety, and efficacy. Upadacitinib and abrocitinib have the highest short‐term efficacy among the approved systemic therapies. In responders, dupilumab and tralokinumab catch up regarding long‐term efficacy and incremental clinical benefit within continuous use. Recently, the European Medicines Agency has released recommendations for the use of JAKi in patients at risk (cardiovascular and thromboembolic diseases, malignancies, (former) smoking, and age ≥65 years). Furthermore, we give an overview on emerging therapies currently in Phase III trials. Among the topical therapies, tapinarof (aryl hydrocarbon receptor), ruxolitinib (JAK1/2i), delgocitinib (pan‐JAKi), asivatrep (anti‐transient receptor potential vanilloid), and phosphodiesterase‐4‐inhibitors (roflumilast, difamilast) are discussed. Among systemic therapies, current data on cord‐blood‐derived mesenchymal stem cells, CM310 (anti IL‐4Rα), nemolizumab (anti‐IL‐31RA), anti‐OX40/OX40L‐antibodies, neurokinin‐receptor‐1‐antagonists, and difelikefalin (κ‐opioid‐R) are reported.

Background: Atopic dermatitis (AD) and psoriasis vulgaris (PV) are almost mutually exclusive diseases with different immune polarizations, mechanisms and therapeutic targets. Switches to the other disease (“Flip‐Flop” [FF] phenomenon) can occur with or without systemic treatment and are often referred to as paradoxical reactions under biological therapy.Methods: The objective was to develop a diagnostic algorithm by combining clinical criteria of AD and PV to identify FF patients. The algorithm was prospectively validated in patients enrolled in the CK‐CARE registry in Bonn, Germany. Afterward, algorithm refinements were implemented based on machine learning.Results: Three hundred adult Caucasian patients were included in the validation study (n = 238 with AD, n = 49 with PV, n = 13 with FF; mean age 41.2 years; n = 161 [53.7%] female). The total FF scores of the PV and AD groups differed significantly from the FF group in the validation data (p < .001). The predictive mean generalized Youden‐Index of the initial model was 78.9% [95% confidence interval 72.0%–85.6%] and the accuracy was 89.7%. Disease group‐specific sensitivity was 100% (FF), 95.0% (AD), and 61.2% (PV). The specificity was 89.2% (FF), 100% (AD), and 100% (PV), respectively.Conclusion: The FF algorithm represents the first validated tool to identify FF patients.

Background: Autoreactive immunoglobulin E (IgE) antibodies to self‐peptides within the epidermis have been identified in patients with atopic dermatitis (AD). Prevalence, concomitant diseases, patient characteristics, and risk factors of IgE autoantibody development remain elusive. We aimed to determine IgE autoantibodies in serum samples (n = 672) from well‐characterized patients with AD and controls (1.2–88.9 years).Methods: Atopic dermatitis patients were sub‐grouped in AD with comorbid Type‐2 diseases (“AD + Type 2”; asthma, allergic rhinitis, food allergy, n = 431) or “solely AD” (n = 115). Also, subjects without AD but with Type‐2 diseases (“atopic controls,” n = 52) and non‐atopic “healthy controls” (n = 74) were included. Total proteins from primary human keratinocytes were used for the immunoassay to detect IgE autoantibodies. Values were compared to already known positive and negative serum samples.Results: Immunoglobulin E autoantibodies were found in 15.0% (82/546) of all analyzed AD‐patients. “AD + Type 2” showed a higher prevalence (16.4%) than “solely AD” (9.6%). “Atopic controls” (9.6%) were comparable with “solely AD” patients, while 2.7% of healthy controls showed IgE autoantibodies. Of those with high levels of IgE autoantibodies, 15 out of 16 were patients with “AD + Type 2”. AD patients with IgE autoantibodies were younger than those without. Patients with IgE autoreactivity also displayed higher total serum IgE levels. Factors that affected IgE autoantibody development were as follows: birth between January and June, cesarean‐section and diversity of domestic pets.Conclusions: Immunoglobulin E autoantibodies in AD seem to associate with the presence of atopic comorbidities and environmental factors. The potential value of IgE autoantibodies as a predictive biomarker for the course of AD, including the atopic march, needs further exploration.

Background: Atopic dermatitis (AD) has long been regarded as a primarily pediatric disease. However, there is growing evidence for a high rate of adult‐onset AD. We aimed to characterize factors associated with adult‐onset versus childhood‐onset AD and controls.Methods: We analyzed cross‐sectional data of the CK‐CARE‐ProRaD cohorts Bonn, Augsburg, Davos, Zürich of 736 adult patients stratified by age of AD onset (childhood‐onset non‐atopic, aOR = 4.03 [1.20–13.45] vs. controls^atopic). Conjunctivitis showed a negative association versus controls^atopic (aOR = 0.36 [0.14–0.91]). Food allergy (aOR = 2.93 [1.44–5.96]), maternal food allergy (aOR = 9.43 [1.10–80.95]), palmar hyperlinearity (aOR = 2.11 [1.05–4.25]), and academic background (aOR = 2.14 [1.00–4.54]) increased the odds of childhood‐onset AD versus controls^atopic. Shared AD‐associated factors were maternal AD (4‐34x), increased IgE (2‐20x), atopic stigmata (2‐3x) with varying effect sizes depending on AD onset and control group. Patients with adult‐compared to childhood‐onset had doubled odds of allergic rhinitis (aOR = 2.15 [1.12–4.13]), but reduced odds to feature multiple (3–4) atopic comorbidities (aOR = 0.34 [0.14–0.84]). Adult‐onset AD, particularly onset ≥61 years, grouped mainly in clusters with low contributions of personal and familial atopy and high frequencies of physical inactivity, childhood‐onset AD, particularly infant‐onset, mainly in “high‐atopic”‐clusters.Conclusions: The identified associated factors suggest partly varying endo‐ and exogeneous mechanisms underlying adult‐onset versus childhood‐onset AD. Our findings might contribute to better assessment of the individual risk to develop AD throughout life and encourage prevention by non‐smoking and physical activity as modifiable lifestyle factors.