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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. [ABSTRACT FROM AUTHOR]

This article discusses the impact of topical anti-inflammatory therapy on the Toll-like receptor 2 (TLR2) response in epidermal dendritic cells (DC) in patients with atopic dermatitis (AD). The study found that AD patients have an inhibited maturation response in their Langerhans cells (LC), a type of DC, compared to healthy controls. However, after topical anti-inflammatory treatment, the ability of LC to respond to TLR2 ligands was restored. The study suggests that anti-inflammatory treatment can restore TLR2 signaling in DC in AD, even before visible improvements in the skin occur. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a severe inflammatory skin disease. Langerhans cells and inflammatory dendritic epidermal cells (IDEC) are located in the epidermis of AD patients and contribute to the inflammatory processes. Both express robustly the high-affinity receptor for IgE, Fc«RI, and thereby sense allergens. A beneficial role of vitamin D3 in AD is discussed to be important especially in patients with allergic sensitization. We hypothesized that vitamin D3 impacts Fc«RI expression and addressed this in human ex vivo skin, in vitro Langerhans cells, and IDEC models generated from primary human precursor cells. We show in this article that biologically active vitamin D3 [1,25(OH)2-D3] significantly downregulated Fc«RI at the protein and mRNA levels of the receptor's a-chain, analyzed by flow cytometry and quantitative RT-PCR. We also describe the expression of a functional vitamin D receptor in IDEC. 1,25(OH)2-D3-mediated Fc«RI reduction was direct and resulted in impaired activation of IDEC upon Fc«RI engagement as monitored by CD83 expression. Fc«RI regulation by 1,25(OH)2-D3 was independent of maturation and expression levels of microRNA-155 and PU.1 (as upstream regulatory axis of Fc«RI) and transcription factors Elf-1 and YY1. However, 1,25(OH)2-D3 induced dissociation of PU.1 and YY1 from the FCER1A promotor, evaluated by chromatin immunoprecipitation. We show that vitamin D3 directly reduces Fc«RI expression on dendritic cells by inhibiting transcription factor binding to its promotor and subsequently impairs IgE-mediated signaling. Thus, vitamin D3 as an individualized therapeutic supplement for those AD patients with allergic sensitization interferes with IgE-mediated inflammatory processes in AD patients. [ABSTRACT FROM AUTHOR]

Pharmaceuticals and personal care products are omnipresent in wastewater world-wide. In order to predict their sorption quantities onto sludge in wastewater treatment plants (WWTPs), the solid–water distribution coefficients (Kd values) of selected pharmaceuticals (antiphlogistics, estrogens, lipid regulators, anti-epileptic and cytostatic agents) and polycyclic musk fragrances (HHCB, AHTN) were determined in primary and secondary sludges taken from a German municipal WWTP. For the Kd determination, batches of primary and secondary sludge slurries were spiked with the respective target compounds and slowly stirred under defined conditions (e.g. an argon atmosphere). Finally, the water and solid sludge phases were analysed. The Kd values of pharmaceuticals ranged from <1 to 500Lkg-1, while those for the polycyclic musk fragrances AHTN and HHCB proved to be up to 5300 and 4900Lkg-1, respectively. The primary and secondary sludge showed significant differences for some pharmaceuticals such as Diclofenac and Cyclophosphamide due to the different pH and composition of the two sludges. The removal rate from the water phase caused by sorption in a WWTP can be reasonably predicted on the basis of the Kd values. [Copyright &y& Elsevier]

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., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Circulating phospholipids have been considered as biomarkers and therapeutic targets in multiple disorders. Atopic dermatitis (AD) is the most common inflammatory skin disease. Although there are numerous studies having addressed stratum corneum lipids in the context of epidermal barrier, little is known about the circulating lipids in patients with AD. In this study, we explored the changes of serum phospholipids in AD using liquid chromatography coupled to tandem mass spectrometry and sought serum lipids' contribution to clinical status. Several serum levels of phospholipids were altered in the AD group (n = 179) compared with that in healthy controls (n = 47) and patients without AD with atopic comorbidities (n = 22); lipids exhibiting the apparent changes included increased sphingosine, multiple variants of phosphatidylcholine, and decreased ceramide (16:0) in patients with AD. Moreover, serum levels of sphingosine correlated with the severity of AD, and sphingosine and ceramide(16:0) were also detected as the risk-increasing effect and risk-reduction effect of AD, respectively. In summary, alterations in the serum concentration of phospholipids are seen in patients with AD. Although more detailed investigations will be needed to evaluate the significance of the changes in circulating lipids in AD, these findings can provide, to our knowledge, previously unreported insight into AD's pathogenesis and therapeutic strategies., (© 2021 The Authors.)

Atopic dermatitis (AD) is a severe inflammatory skin disease. Langerhans cells and inflammatory dendritic epidermal cells (IDEC) are located in the epidermis of AD patients and contribute to the inflammatory processes. Both express robustly the high-affinity receptor for IgE, FcεRI, and thereby sense allergens. A beneficial role of vitamin D 3 in AD is discussed to be important especially in patients with allergic sensitization. We hypothesized that vitamin D 3 impacts FcεRI expression and addressed this in human ex vivo skin, in vitro Langerhans cells, and IDEC models generated from primary human precursor cells. We show in this article that biologically active vitamin D 3 [1,25(OH) 2 -D 3 ] significantly downregulated FcεRI at the protein and mRNA levels of the receptor's α-chain, analyzed by flow cytometry and quantitative RT-PCR. We also describe the expression of a functional vitamin D receptor in IDEC. 1,25(OH) 2 -D 3 -mediated FcεRI reduction was direct and resulted in impaired activation of IDEC upon FcεRI engagement as monitored by CD83 expression. FcεRI regulation by 1,25(OH) 2 -D 3 was independent of maturation and expression levels of microRNA-155 and PU.1 (as upstream regulatory axis of FcεRI) and transcription factors Elf-1 and YY1. However, 1,25(OH) 2 -D 3 induced dissociation of PU.1 and YY1 from the FCER1A promotor, evaluated by chromatin immunoprecipitation. We show that vitamin D 3 directly reduces FcεRI expression on dendritic cells by inhibiting transcription factor binding to its promotor and subsequently impairs IgE-mediated signaling. Thus, vitamin D 3 as an individualized therapeutic supplement for those AD patients with allergic sensitization interferes with IgE-mediated inflammatory processes in AD patients., (Copyright © 2021 by The American Association of Immunologists, Inc.)

Background: It is widely accepted that local anesthetics with epinephrine should not be used in areas served by terminal vessels. There is no evidence in studies for this in penile surgery, and given the anatomy of the penis, perfusion complications are highly unlikely. The goal of this study was to show that a penile block using a local anesthetic with epinephrine is safe., Patients and Methods: In a follow-up study between 2005 and 2010, we analyzed 95 patients who got a penile ring block with subcutaneous infusion anesthesia (SIA). The SIA solution consisted of ropivacaine and lidocaine (0.11% and 0.21%) plus epinephrine., Results: There were no anesthetic complications. Short-term negative postoperative occurrences (<72 hrs.) were swelling (42%), problems with suture material (22%), pain (19%), hematoma and paresthesia (each 13%), erectile dysfunction (12%), small-area skin necrosis after wound healing without requiring further surgery (13%), micturition disorders (7%), and wound infection (6%). Two patients on anticoagulation therapy had postoperative bleeding requiring revision surgery. 5% of the patients were given further analgesic sedation. 19% complained about postoperative pain. Persistent complaints (maximum 6 months) were disturbances of skin sensation (7%), swelling (4%), and redness and micturition disorders (3% each)., Conclusions: Supplementing a local anesthetic with epinephrine in penis operations has many advantages, including high patient satisfaction, relatively painless infiltration, low complication rates, improved view of the operating field, and an extended effect of anesthetics with a prolonged reduction in pain. Because of the anatomy of the organ, there is no risk of necrosis related to using a subcutaneous penile ring block. Thus the view that epinephrine should not be used in penis procedures is obsolete., (© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Dendritic cells (DCs) have been recognized as key players bridging innate and adaptive immune systems. They control the balance of the adaptive immune response, and the functional behavior of DCs is mainly dictated by their microenvironment. Atopic dermatitis (AD) is a paradigmatic disease where the inflammatory microenvironment has a deep impact on DCs. The emergence of IgE-mediated sensitization is tightly related to the impact of locally released cytokines by either keratinocytes, T cells, or other cells involved in the inflammatory reaction. This review will focus on the recent and relevant findings in the field of immunobiology of DCs and their role in AD.